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Noted This Week - 2022

Archive of cancer-related news briefs, by week, for 2022


December 2022

December 16–21

  • In the omnibus spending bill slated for congressional approval by December 23, the NIH and NCI will receive budget increases of $2.5 billion (5.6%) and $407.6 million (5.9%), respectively, for fiscal year 2023. The FDA will receive $3.5 billion in discretionary funding, an increase of $226 million. This would bring the FDA’s total budget, including the fees that the agency collects as part of the drug approval process, to $6.6 billion for the year.
  • Speaking of the FDA: Provisions related to accelerated drug approvals were included in the omnibus spending bill as well. They would allow the agency to require confirmatory trials to start prior to granting accelerated approval and require status updates every 6 months. In addition, the legislation directs the FDA to establish an accelerated approval advisory council.
  • Makers of both FDA-approved KRASG12C inhibitors announced positive trial results for their drugs.
    • In a phase I/II trial involving 38 patients with KRASG12C-mutant pancreatic cancer who had already received at least one systemic therapy, Amgen’s sotorasib (Lumakras) yielded an objective response rate (ORR) of 21%, a median progression-free survival (PFS) of 4 months, and overall survival of 6.9 months (N Engl J Med 2022 Dec 21 [Epub ahead of print]).
    • Mirati’s phase I/II trial of adagrasib (Krazati)—with and without the EGFR inhibitor cetuximab (Erbitux; Lilly)—showed efficacy in patients with metastatic colorectal cancer who had already received multiple treatments (N Engl J Med 2022 Dec 21 [Epub ahead of print]). A response to adagrasib alone was reported in 19% of 43 evaluable patients, with a median PFS of 5.6 months; among 28 evaluable patients who received the drug combination, 46% responded and the median PFS was 6.9 months.
  • Ferring Pharmaceuticals announced that the FDA approved nadofaragene firadenovec-vncg (Adstiladrin) to treat adults with high-risk bacillus Calmette–Guérin–unresponsive non–muscle invasive bladder cancer with carcinoma in situ with or without papillary tumors. In a study involving 98 patients with the condition, the complete response (CR) rate was 51%—with 46% of these patients maintaining a CR for at least a year—and the median duration of response (DOR)was 9.7 months. The most common adverse events were increased glucose and triglyceride levels, instillation site discharge, and fatigue.

Earlier This Year:

 ::  January  ::  February  ::  March  ::  April  ::  May  ::  June  ::  July  ::  August  ::  September  ::  October  ::  November

Noted This Week Archive:

 ::  2023  ::  2022  ::  2021  ::  2020  ::  2019  ::  2018  ::  2017  ::  2016  ::  2015  ::  2014  ::  2013  ::  2012  ::  2011

  • Jazz Pharmaceuticals said it will pay $325 million to Zymeworks to develop and commercialize zanidatamab in the United States, Europe, and Japan, a deal could ultimately be worth $1.76 billion, plus royalties, for Zymeworks. Two pivotal trials of the anti-HER2 bispecific antibody are underway—one in biliary tract cancer (BTC) and one in HER2-positive gastroesophageal adenocarcinoma; additional trials are examining zanidatamab’s effectiveness in breast and colorectal cancers and other solid tumors. Earlier in the week, Zymeworks released top-line data from the BTC trial showing an ORR of 41.3% and a median DOR of 12.9 months.
  • The New York Times reported that a life-size bronze statue of Henrietta Lacks will be erected next year in Roanoke, VA, her hometown. The statue will grace a plaza that had been named after Confederate General Robert E. Lee; it will be renamed in her honor. Lacks’s cervical cancer cells, which were taken without her consent prior to her death from the disease in 1951 and immortalized as HeLa cells, have led to numerous medical treatments and discoveries.

December 9–15

Recent happenings, as well as news from the 64th American Society of Hematology (ASH) Annual Meeting and Exposition.

Recent happenings:

  • The FDA granted accelerated approval to adagrasib (Krazati; Mirati) to treat advanced KRASG12C-mutated non–small cell lung cancer that advances on or after platinum-based chemotherapy and an immune checkpoint inhibitor. In the single-arm, phase II KRYSTAL-1 study, patients who received adagrasib had an objective response rate of 43%, with a median duration of response of 8.5 months. Adagrasib is the second KRASG12C inhibitor to be approved in the United States; Amgen’s sotorasib (Lumakras) was greenlighted in May 2021 for the same indication.
  • Clovis Oncology filed for bankruptcy and sold the rights to FAP-2286, a peptide-targeted radionuclide therapy and imaging agent that targets fibroblast activation protein (FAP), to Novartis for $50 million and up to $333.75 million more for achieving certain development milestones and $297 million for meeting certain sales milestones. Clovis currently holds the rights to the PARP inhibitor rucaparib (Rubraca) and three other targeted radionuclides but is talking with other companies about selling them.
  • Several senators and representatives introduced new legislation related to cancer—the Comprehensive Cancer Survivorship Act—for consideration by the U.S. Congress. If passed, the legislation would support Medicare coverage for developing treatment plans and follow-up care to address long-term side effects of treatment; a review of best practices for survivorship navigation programs; an evidence-based cancer survivorship research program; and Medicaid coverage of fertility services if treatments could lead to infertility. The bill would also promote standard-of-care and survivorship plans for children transitioning from oncology care to primary care.

ASH meeting news:

  • The FDA approved atezolizumab (Tecentriq; Genentech) for inoperable or metastatic alveolar soft part sarcoma in adults and children age 2 and older. Efficacy was evaluated in Study ML39345, an open-label, single-arm study involving 49 patients with the disease. The overall response rate was 24%; of the 12 patients who responded, 67% experienced a response lasting 6 months or longer, and 42% had a response lasting at least 12 months. The most common adverse reactions were musculoskeletal pain, fatigue, rash, and cough.
  • Do patients with relapsed/refractory acute myeloid leukemia (AML) after initial induction therapy need to have a complete response (CR) to salvage chemotherapy before having an allogeneic stem cell transplant (SCT)? According to groundbreaking research presented at the plenary session of the ASH annual meeting, held December 10–13 in New Orleans, LA, the practice-changing answer is no. Rather, based on the results of the noninferiority randomized ASAP trial, researchers concluded that these patients should undergo SCT ASAP.
  • Also at the ASH plenary, researchers dismantled the long-held belief that patients with mantle cell lymphoma (MCL) should initially be treated with intensive chemoimmunotherapy plus an autologous SCT (ASCT). Based on studies showing solid responses to ibrutinib (Imbruvica; Janssen/Pharmacyclics) in relapsed MCL and in older patients as a first-line therapy, researchers assessed whether the BTK inhibitor could effectively be a first-line therapy in younger patients. They found that taking ibrutinib and skipping ASCT or having just the ASCT yielded similar failure-free survival after 3 years. They also found that adding ibrutinib to ASCT was superior to having an ASCT alone.
  • Plenary session attendees gave a standing ovation to Irving Weissman, MD, of Stanford Institute for Stem Cell Biology and Regenerative Medicine in California, who won the Wallace H. Coulter Award for Lifetime Achievement in Hematology. Among his numerous accomplishments, Weissman is credited with isolating blood-forming stem cells from mice and humans; isolating blood-forming stem cells free from cancer cells so that they could be reinfused into patients following chemotherapy; and discovering that an anti-CD47 antibody combined with azacitidine could effectively treat AML. Named for the inventor of the Coulter Counter, the standardized method to count different types of blood cells, the prize is the highest honor bestowed by ASH.
  • Researchers reported that patients undergoing an SCT for cancer do not derive any benefit from following a restrictive diet—which forbids fresh fruits and vegetables and foods that haven’t been cooked to at least 175⁰F—prescribed during the 4 to 6 weeks they spend as inpatients. Commenting on the research, Mikkael Sekeres, MD, MS, of the Sylvester Comprehensive Cancer Center in Miami, FL, said that it "upends the current dogma. For decades, we have essentially been feeding patients gruel in the hospital under the auspices of a neutropenic diet. The theory is a good one—that we’re minimizing the risk of infections in people who are severely compromised." But based on the new findings, he argued that "we should eliminate these silly neutropenic diets and let people eat what they want and give them a much better quality of life while they’re in the hospital."
  • Also at the ASH meeting, researchers reported that in 155 patients with relapsed/refractory diffuse large B-cell lymphoma enrolled in a phase II trial of glofitamab (Genentech), 39% had a CR after 12.6 months of follow-up. The CD20xCD3 bispecific antibody has a distinct mechanism of action in that it boasts a "novel 2:1 tumor–T-cell binding configuration that confers bivalency for CD20 (B cells) and monovalency for CD3 (T cells), leading to the engraftment and redirection of patients’ existing T cells to eliminate malignant B cells," according to a report published concurrently in The New England Journal of Medicine (N Engl J Med 2022;387:2220–31).

December 2–8

  • At the 2022 San Antonio Breast Cancer Symposium (SABCS) in Texas, December 6–10, TROPiCS-02 trial researchers reported that sacituzumab govitecan (Trodelvy; Gilead) extends survival compared with physician’s choice of chemotherapy for patients with hormone receptor (HR)–positive, HER2-negative metastatic breast cancer—regardless of Trop-2 expression. Among patients with the highest levels of Trop-2, the median progression-free survival (PFS) was 6.4 months and 4.1 months, and overall survival (OS) was 14.6 months and 11.3 months, for sacituzumab govitecan and chemotherapy, respectively; among patients with the lowest Trop-2 levels, PFS was 5.3 months and 4 months, and OS was 14.4 and 11.2 months, respectively. An antibody–drug conjugate, sacituzumab govitecan is approved to treat triple-negative breast cancer.
  • According to results of the POSITIVE trial presented at the SABCS, younger women with early-stage HR-positive breast cancer who pause endocrine therapy to try to get pregnant do not have higher rates of disease recurrence than those who continue therapy. The study enrolled 518 women age 42 or younger who had completed 18 to 30 months of adjuvant therapy and were willing to pause treatment for about 2 years to try to conceive. Their 3-year rate of recurrence was 8.9%, which was similar to the 9.2% rate in an external control cohort; 74% had at least one pregnancy—and 63.8% had at least one baby—rates on par with the general public. More than 76% have resumed therapy.
  • Also at the SABCS, researchers reported that non-Hispanic Black women with HR-positive/HER2-negative, lymph node–positive breast cancer did not fare as well as non-Hispanic whites, Asians, and Hispanics, despite similar 21-gene recurrence scores. The 4,048 uniformly treated patients in the RxPONDER trial had no more than three positive axillary lymph nodes and low or intermediate risk of cancer recurrence, but non-Hispanic Black women had the lowest 5-year disease-free survival rate—87.2%—compared with 91.5% for non-Hispanic whites, 93.9% for Asians, and 91.4% for Hispanics. The differences, the researchers said, were not due to treatment duration or treatment noncompliance, suggesting that biological factors contribute to survival rates.
  • Beam Therapeutics announced that the FDA lifted the clinical hold on BEAM-201 for the treatment of relapsed/refractory T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma and cleared the drug for clinical trials. BEAM-201 is an anti-CD7 allogeneic chimeric antigen receptor T-cell investigational drug. The FDA put a hold on the base-edited, off-the-shelf therapy in August, seeking additional analyses of off-target editing experiments, among other things.
  • MEI Pharma and Kyowa Kirin will discontinue development of zandelisib, an investigational PI3K inhibitor for B-cell malignancies, outside of Japan. Based on data from the single-arm, phase II MIRAGE trial evaluating the drug in Japanese patients with relapsed/refractory indolent B-cell non-Hodgkin lymphoma, the companies had hoped the drug might garner FDA approval. However, the agency indicated that a randomized trial would be needed and that single-arm studies are insufficient to adequately assess the potential risks and benefits of this class of drugs. The companies will continue clinical trials in Japan.


November 2022

November 18–December 1

  • Roche announced the withdrawal of atezolizumab (Tecentriq) to treat adults with certain bladder cancers—namely those with newly diagnosed locally advanced or metastatic urothelial carcinoma who cannot receive chemotherapy containing cisplatin and whose tumors express PD-L1 or aren’t eligible for any platinum chemotherapy regardless of PD-L1 expression. The decision was made based on disappointing overall survival in the phase III IMvigor130 trial, which was required by the FDA to convert the drug’s 2017 accelerated approval to full approval for these indications.
  • Spectrum Pharmaceuticals "deprioritized" the development of poziotinib to treat non–small cell lung cancer with HER2 exon 20 insertion mutations after the FDA said, among other things, that the drug cannot be approved unless a randomized controlled study to generate more data on its potential benefit is underway. To save money the company will reduce its R&D workforce by 75% and "focus efforts on driving growth" for eflapegrastim (Rolvedon). That drug, which reduces infection risk in adults taking anticancer drugs associated with febrile neutropenia, was approved in September.
  • The FDA approved olutasidenib (Rezlidhia; Rigel Pharmaceuticals) for adults with relapsed/refractory acute myeloid leukemia with a susceptible IDH1 mutation; the agency also approved the Abbott RealTime IDH1 Assay to determine which patients are eligible to receive the drug. The decision was based on the results of Study 2102-HEM-101, an open-label, single-arm trial that included 147 adults with the disease. The rate of complete remission was 32% and the rate of complete remission with partial hematologic recovery was 2.7%; the median duration of these responses was 25.9 months.
  • A combination of radiation and the PD-L1 inhibitor durvalumab (Imfinzi; AstraZeneca) could rev up an immune response against head and neck cancers that are unrelated to the human papillomavirus (HPV) prior to surgery (Nature Cancer 2022;3:1300–17). Among 21 patients in a phase I/Ib dose-escalation study, 75% had a major pathologic response or complete response, a number that increased to 89% in an expansion cohort that received an optimal radiation dose; none of these responders have had adjuvant radiation or chemotherapy. Responses to checkpoint inhibitors alone have typically been poor among patients with these tumors.
  • Y-mAbs announced that the FDA will not approve omburtamab to treat central nervous system/leptomeningeal metastasis from neuroblastoma. According to the company, the FDA recommended that Y-mAbs meet with the agency "to discuss adequate and well-controlled trial design to demonstrate substantial evidence of effectiveness and a favorable benefit–risk profile." Y-mAbs said it will assess "the implications of the [letter] and its plans for the omburtamab program."
  • Pfizer announced that it will invest $1.26 billion to expand its manufacturing facility in Dublin, Ireland, Endpoints News reported. The expansion will feature the construction of a new facility that will add more lab space and greatly improve the company’s ability to manufacture biological drugs for cancer and rare diseases, among others. Construction, the publication noted, will take 3 years and will likely start in 2024. Approximately 400 to 500 jobs will be added there.
  • Although cervical cancer screening and related tests and procedures have declined by 55% in women over age 65 in the past two decades, more than 1.3 million older women in the United States received cytology and/or HPV tests and related care in 2019 (JAMA Intern Med 2022 Nov 22 [Epub ahead of print]). Medicare paid about $83.5 million for these services, which potentially caused complications and unnecessary discomfort for these women—about 3% of whom were older than 80. The U.S. Preventive Services Task Force recommends against cervical cancer screening in women 65 and older at average risk of the disease who’ve had "adequate" screening previously; the researchers say additional study of the issue given the "unclear clinical appropriateness" of such care is needed.

November 11–17

  • The FDA granted accelerated approval to mirvetuximab soravtansine-gynx (Elahere; ImmunoGen), an antibody–drug conjugate (ADC), to treat women with folate receptor alpha (FRα)–positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who had already received one to three systemic therapies. Efficacy was measured in the Study 0417 trial: Among 104 evaluable patients, the overall response rate was 31.7% and the median duration of response was 6.9 months. Of note, the drug label includes a boxed warning about ocular toxicity.
  • The agency also approved the VENTANA FOLR1 (FOLR-2.1) RxDx Assay (Roche) companion diagnostic device to check for FRα positivity and determine women’s eligibility to receive mirvetuximab soravtansine for ovarian cancer.
  • Another development in the world of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer—GSK said it will limit the second-line maintenance indication of the PARP inhibitor niraparib (Zejula) to patients with deleterious or suspected deleterious germline BRCA mutations. The company made the decision based on a request from the FDA after the agency reviewed overall survival (OS) data from the ENGOT-OV16/NOVA phase III trial showing a hazard ratio of 1.06 in patients without BRCA mutations. Niraparib can still be used as an initial maintenance therapy in patients who have a complete or partial response to platinum-based chemotherapy.
  • Ipsen announced that its irinotecan liposome injection (Onivyde) plus chemotherapy yielded significant improvement in OS in patients with newly diagnosed metastatic pancreatic ductal adenocarcinoma compared with a regimen of nab-paclitaxel and gemcitabine; results will be presented at an upcoming medical meeting. Ipsen, which plans to file for regulatory approval, purchased the drug from Merrimack Pharmaceuticals in 2017 for $575 million plus an additional $225 million if the FDA OK’s the drug, STAT reported. Merrimack was shuttered in 2019, so the money would be distributed to stockholders as dividends.
  • Sequencing giant Illumina cut 5% of its global workforce, according to a filing with the U.S. Securities and Exchange Commission, which amounts to about 500 lost jobs. In the document, Illumina said it is "proactively realigning…operating expenses to reflect the current macro-economic environment while maintaining focus on its innovation roadmap and sustainable long-term growth." The company, which has a significant presence in oncology, did not specify the areas of the organization that would be most affected.
  • Seagen’s brentuximab vedotin received its first approval for a pediatric indication: The FDA greenlighted use of the CD30-directed ADC plus chemotherapy for children ages 2 and older with newly diagnosed high-risk classical Hodgkin lymphoma based on a phase III trial comparing the combination with chemotherapy alone. The study’s primary endpoint, median event-free survival (EFS), wasn’t reached in either trial arm. However, at a median follow-up of 42.1 months, the 3-year EFS was 92.1% in the brentuximab arm compared with 82.5% in the chemotherapy arm; OS at 3 years was 99.3% and 98.5%, respectively—thus a 59% reduction in the risk of death or other event, such as disease progression (N Engl J Med 2022;387:1649–60).

November 4–10

  • In a filing with the U.S. Securities and Exchange Commission, Clovis Oncology disclosed that it might be forced to file for bankruptcy amid declining sales of its PARP inhibitor, rucaparib (Rubraca). Further complicating the company’s financial future, the FDA, according to Clovis, has recently focused on mature overall survival (OS) data "for drugs previously approved based on achieving PFS as a primary endpoint," which has "led to withdrawals of certain later-line indications in ovarian cancer" for rucaparib; as well, the FDA could limit the use of the drug in earlier-stage disease, an indication that accounts for "a substantial portion" of revenue. To save money, Clovis laid off 115 employees.
  • GSK announced that in the phase III, head-to-head superiority trial dubbed DREAMM-3, belantamab mafodotin (Blenrep) did not meet its primary endpoint of progression-free survival (PFS) in patients with relapsed/refractory multiple myeloma (RRMM) compared with a combination of pomalidomide and dexamethasone. Although the median PFS was longer for belantamab mafodotin vs. the combination—11.2 months vs. 7 months—the hazard ratio was 1.03; at the time of the data analysis, OS data were not mature. Belantamab mafodotin had been granted accelerated approval by the FDA to treat adults with RRMM who have already received at least four therapies, including an anti-CD38 mAb, a proteasome inhibitor, and an immunomodulatory agent.
  • To treat metastatic non–small cell lung cancer (NSCLC), the FDA approved the anti-CTLA4 drug tremelimumab (Imjudo; AstraZeneca) in combination with the PD-L1 inhibitor durvalumab (Imfinzi; AstraZeneca) and platinum-based chemotherapy for patients without EGFR or ALK aberrations. In the POSEIDON trial, patients who received the drug trio had a median OS of 14 months compared with 11.7 months in patients who received chemotherapy alone; median PFS was 6.2 months and 4.8 months, respectively. The most common adverse reactions were nausea, fatigue, and decreased appetite.
  • The FDA approved the PD-1 inhibitor cemiplimab (Libtayo; Regeneron) plus platinum-based chemotherapy for adults with NSCLC without EGFR, ALK, or ROS1 mutations. For the 466 patients in Study 16113, those who received the combination experienced a median OS of 21.9 months compared with 13 months for those who received chemotherapy alone; median PFS was 8.2 months and 5 months, respectively. The most common adverse reactions were alopecia, musculoskeletal pain, nausea, and fatigue.
  • ADC Therapeutics announced that it will pause development of camidanlumab tesirine (cami) for the treatment of relapsed/refractory Hodgkin lymphoma despite positive results in a phase II trial that yielded an overall response rate of 70% and a complete response rate of 33%. That’s because the FDA signaled that a randomized, confirmatory phase III trial of cami "must be well underway and ideally fully enrolled" before the agency would be likely to consider accelerated approval for the antibody–drug conjugate. The company said it will take at least 2 years for such a trial to be fully enrolled.
  • Researchers reported that a new tool can trace how certain breast cancers grow and spread, as well as how resistance develops and why some therapies fail (Nature 2022 Nov 9 [Epub ahead of print]). "An important insight from our research is that it may not be the genetic changes alone that are the reason that the cancer cells survive and spread; it could also be where they are," said co–senior author Mats Nilsson, PhD, of Stockholm University in Sweden. "It may also offer explanations about why some treatments only work in some individuals, even if they have similar mutations to others, as the tumours are found in different areas of the breast."

October 2022

October 28–November 3

  • Researchers reported that children with high-risk Hodgkin lymphoma were 10% less likely to relapse with brentuximab vedotin (Adcetris; Seagen), an antibody–drug conjugate targeting CD30, plus standard chemotherapy than with standard chemotherapy alone (N Engl J Med 2022;387:1649–60). In a phase III trial, 587 patients ages 2 to 21 were randomly assigned to one of the two treatments. After a median of 42.1 months, the 3-year event-free survival was 92.1% in the brentuximab vedotin group compared with 82.5% in the group that received standard care; overall survival at 3 years was 99.3 % compared with 98.5%, respectively.
  • An experimental breast cancer vaccine yielded strong immune responses in patients with advanced, metastatic HER2-positive disease, researchers reported (JAMA Oncol 2022 Nov 3 [Epub ahead of print]). In a phase I, single-arm trial, 66 women received the vaccine and were followed for a median of nearly 10 years. Typically, about half of patients with similar stages of HER2-positive breast cancer would be alive after 5 years of treatment, but 80% of the study participants are still alive; side effects were mild, with the most common being redness and swelling at the injection site.
  • The FDA approved cobimetinib (Cotellic; Genentech) to treat adults with histiocytic neoplasms, a group of rare blood diseases that includes Erdheim-Chester disease, Rosai-Dorfman disease, and Langerhans cell histiocytosis. The decision was based on a single-arm, single-center trial showing that cobimetinib yielded an objective response rate of 76.9% with PET and 46.2% by RECIST criteria in 26 patients after a median follow-up of 11.4 months. An oral MEK1/2 inhibitor, cobimentinib is also approved for use with vemurafenib (Zelboraf; Genentech) for the treatment of melanoma with a BRAF V600E mutation.
  • All 16 members of an FDA advisory committee recommended against the approval of 131I-omburtamab (Y-mAbs Therapeutics) to treat children with neuroblastoma who have central nervous system/leptomeningeal metastases. Committee members said that the data didn’t demonstrate a clear response rate and that more data from randomized controlled trials are needed. A radiolabeled antibody, 131Iomburtamab targets B7-H3 on neuroblastoma cells.
  • Researchers found that a polygenic hazard score based on 290 genetic variants (PHS290) might be an effective tool to predict a man’s genetic risk of deadly prostate cancer. In a retrospective analysis of 590,750 men in the Million Veteran Program, the researchers looked for associations between genetic and other risk factors—including race, ethnicity, and family history of prostate cancer—with age at diagnosis of prostate cancer and death from the disease (J Natl Cancer Inst 2022 Oct 28 [Epub ahead of print]). The hazard ratio for lethal prostate cancer was 4.42 for men in the highest 20% of PHS290 compared with those in the lowest 20%.

October 21–27

  • The FDA granted accelerated approval to teclistamab-cqyv (Tecvayli; Janssen Biotech) for the treatment of adults with relapsed/refractory multiple myeloma who have received at least four prior therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 mAb. In the multicohort, single-arm, open-label MajesTEC-1 study, the overall response rate was 61.8%; the estimated duration of response rate was 90.6% at 6 months. Teclistamab is the first BCMA-directed CD3 T-cell engager to receive the FDA's blessing.
  • AstraZeneca announced that the FDA approved tremelimumab (Imjudo), a CTLA4 inhibitor, in combination with its PD-L1 inhibitor, durvalumab, for adults with inoperable hepatocellular carcinoma. The approval was based on overall survival (OS) in 782 patients enrolled in the HIMALAYA trial: Patients who received the drug combination lived a median of 16.4 months compared with 13.8 months in those who received standard sorafenib (Nexavar; Bayer), a multi–tyrosine kinase inhibitor.
  • Alpine Immune Sciences terminated enrollment in its two clinical studies of davoceticept (ALPN-202), which were assessing the investigational CD28 costimulator and dual checkpoint inhibitor as both a monotherapy and in combination with the PD-1 inhibitor pembrolizumab (Keytruda; Merck). The company's decision came after a second patient died of cardiogenic shock in the combination trial.
  • The U.S. Preventive Services Task Force (USPSTF) concluded that "current evidence is insufficient to assess the balance of benefits and harms of visual skin examination by a clinician to screen for skin cancer in adolescents and adults" in a just-released draft recommendation (see https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/skin-cancer-screening). The USPSTF is accepting public comments on the document until midnight on November 21.
  • AstraZeneca's investigational AKT inhibitor, capivasertib, plus fulvestrant could become a treatment option for some patients with breast cancer following disease recurrence or progression on or after endocrine therapy—with or without a CDK4/6 inhibitor. The company announced high-level results from its CAPItello-291 phase III trial showing that the combination "demonstrated a statistically significant and clinically meaningful improvement in progression-free survival [PFS]" compared with fulvestrant alone in all study patients with hormone receptor–positive (HR+), HER2-low, or HER2-negative locally advanced or metastatic disease—and in patients with PIK3CA, AKT1, or PTEN alterations. OS data are not yet mature.
  • Meanwhile, at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, researchers reported that the investigational AKT inhibitor ipatasertib (Genentech) met its primary endpoint—objective response rate—in patients with various tumors harboring AKT1 E17K mutations who were enrolled in a subprotocol of the NCI-MATCH trial. The confirmed partial response rate among 32 evaluable patients, 27 of whom had breast or gynecologic cancers, was 22%; the estimated 6-month PFS rate, a secondary endpoint, was 44%. The researchers said that additional research on ipatasertib is warranted in patients with this mutation.
  • AstraZeneca also announced that its next-generation oral selective estrogen receptor degrader (SERD), camizestrant, significantly improved PFS in patients with advanced HR+ breast cancer compared with fulvestrant in an ongoing trial. The camizestrant results stand in contrast to those of Sanofi's amcenestrant, which didn't prolong PFS, ending that oral SERD's development in August (Cancer Discov 2022 Sep 13 [Epub ahead of print]). Data from the camizestrant phase II SERENA-2 trial will be presented at an upcoming medical meeting.
  • The American Association for Cancer Research and the American Society of Clinical Oncology issued a joint policy statement on the use of electronic nicotine delivery systems, also called ENDS (Clin Cancer Res 2022 Oct 26 [Epub ahead of print]; J Clin Oncol 2022 Oct 26 [Epub ahead of print]). "We call for an immediate ban on all non–tobacco-flavored ENDS products that contain natural or synthetic nicotine to reduce ENDS use by youth and adults who never previously used tobacco," the authors write. "Concurrently, evidence-based treatments to promote smoking cessation and prevent smoking relapse to reduce cancer incidence and improve public health remain top priorities for our organizations."

October 14–20

  • Seoul, South Korea's LG Chem announced it will acquire Aveo Oncology for $566 million. Aveo markets the VEGFR tyrosine kinase inhibitor tivozanib (Fotivda), which received FDA approval in 2021 to treat adults with relapsed/refractory advanced renal cell carcinoma who have already tried at least two systemic therapies. In addition to developing tivozanib for other indications, Aveo is advancing four IgG1 mAb drug candidates for the treatment of head and neck squamous cell carcinoma, pancreatic cancer, and other malignancies.
  • Jazz Pharmaceuticals purchased exclusive development and commercialization rights to zanidatamab from Zymeworks for $50 million up-front, with the possibility of total payments reaching $1.76 billion plus royalties for meeting certain regulatory and commercial milestones. A HER2-targeted bispecific antibody, zanidatamab is in pivotal trials as a second-line treatment for HER2-expressing biliary tract cancer (BTC) and as an initial treatment for HER2-positive gastroesophageal adenocarcinoma. Top-line clinical data from the BTC trial is expected by the end of the year.
  • A study warned that women who use chemical hair straighteners may have a greater risk of uterine cancer compared with nonusers (J Natl Cancer Inst 2022 Oct 17 [Epub ahead of print]). Researchers reviewed data from 33,497 patients over nearly 11 years and found 378 cases of uterine cancer; those patients who reported frequent use of the products were more than twice as likely to develop the disease than nonusers—4.05% vs. 1.65%, respectively. Studies have shown an increasing rate of uterine cancer in the United States, particularly among Black women; in this study, 60% of participants identified themselves as Black.
  • The FDA issued a final guidance on developing drugs and biological products to treat acute myeloid leukemia (AML; see www.fda.gov/media/162362/download). With new drugs in the works as alternatives to standard therapies, clinical development programs are becoming more complex due to "the expansion of treatment intent, broadening the intended population, and development of a wide range of new drug classes as alternatives to cytotoxic drugs." The document outlines issues to take into consideration when developing these drugs and discusses the agency's thinking on efficacy endpoints, exploratory and confirmatory trials, and regulatory submission of AML therapeutics.
  • The FDA also published two draft guidances: "Characterizing, Collecting, and Reporting Immune-Mediated Adverse Reactions in Cancer Immunotherapeutic Clinical Trials" and "Tissue Agnostic Drug Development in Oncology" (see www.fda.gov/media/162341/download and https://www.fda.gov/media/162346/download, respectively). In the former, the agency offers recommendations regarding what data on immune-mediated adverse reactions should be collected, evaluated, and included in new drug applications for cancer immunotherapies; in the latter, it outlines "scientific considerations in determining when tissue agnostic oncology drug development may be appropriate…and issues to be addressed during such development." The guidances are available for public comment until December 19.
  • Two partners of the Access to Oncology Medicines (ATOM) Coalition, the Medicines Patent Pool and Novartis, agreed to voluntarily license nilotinib (Tasigna), which is used to treat certain patients with Philadelphia chromosome–positive chronic myeloid leukemia. This means that generic manufacturers can produce nilotinib, even though its patents are in effect, to ensure that the drug is affordable and accessible to patients around the world. The ATOM Coalition helped broker the deal.

October 7–13

  • Three renowned research institutions launched a collaborative effort against pediatric cancers. By combining their intellectual leadership, technical expertise, and institutional funding, researchers at the Broad Institute of MIT and Harvard in Cambridge, MA; Dana-Farber Cancer Institute in Boston, MA; and St. Jude Children's Research Hospital in Memphis, TN, aim to fill gaps in the understanding of the biology of pediatric cancers and accelerate the development of new treatments. With more than $60 million in funding over 5 years, the Pediatric Cancer Dependencies Accelerator project will, among other things, characterize the genetic and epigenetic landscape of pediatric cancers, develop model systems, and identify effective combination therapies.
  • Seattle Washington's Fred Hutchinson Cancer Center announced that Mike and Jackie Bezos and their family will contribute $710.5 million to the institution over the next 10 years to speed research—and increase the breadth of medical breakthroughs—on cancer and infectious diseases. According to the announcement, the landmark gift will help recruit 36 investigators and their staff; provide funding for lab space, equipment, and technology to fuel collaboration; support construction of a new research building; expand the institution's clinical research capabilities and increase the number of clinical trials available to patients, as well as the number and diversity of patients enrolled in trials; and allow the institution's Immunotherapy Integrated Research Center "to expand immune-based strategies for treating cancer and deepen understanding of the biological mechanisms underlying immunotherapy."
  • Continuing a collaboration that began in 2016, Merck will pay Moderna $250 million to jointly develop and commercialize the personalized cancer vaccine mRNA-4157/V940. Moderna is currently conducting a phase II clinical trial of mRNA-4157/V940 in combination with Merck's PD-1 inhibitor pembrolizumab (Keytruda) as an adjuvant treatment for patients with high-risk melanoma. Some trial findings should be available by the end of the year, the companies said.
  • A national survey of 1,100 U.S. women conducted by The Ohio State University Comprehensive Cancer Center in Columbus, OH, found that most women are unaware of the symptoms of inflammatory breast cancer (IBC). Although nearly 80% of respondents knew that a lump is a sign of breast cancer, less than half considered breast redness, pitting or thickening of the skin, or one breast feeling warmer or heavier than the other as symptoms of the disease. IBC is often misdiagnosed because the symptoms mimic those of an infection.
  • While on the subject: Researchers reported that patients with IBC have a high risk for central nervous system (CNS) metastases (Cancer 2022 Oct 10 [Epub ahead of print]). Seeking to determine the incidence and risk factors for CNS metastases in patients with IBC, as well as how long they live, the researchers retrospectively reviewed data from 531 patients with IBC and found that 124 (23%) of them had CNS metastases; median overall survival for these patients was just 0.6 months. Those with a particularly high risk of developing metastases had triple-negative IBC, had visceral metastases, or were diagnosed with IBC at a young age.

September 30–October 6

  • Futibatinib (Lytgobi; Taiho Oncology) earned accelerated approval for FGFR2-aberrant intrahepatic cholangiocarcinoma. The FDA's decision was based on results from a single-arm phase I/II trial: Among 103 patients with previously treated inoperable or advanced/metastatic disease, the objective response rate to futibatinib was 42%, and the median duration of response was 9.7 months. The FGFR1–4 inhibitor's main side effects included diarrhea, fatigue, and musculoskeletal pain.
  • The FDA also greenlighted a companion diagnostic to identify patients with HER2-low inoperable/metastatic breast cancer who may benefit from trastuzumab deruxtecan (Enhertu; Daiichi Sankyo). The test, Roche's PATHWAY anti-HER2/neu (4B5) rabbit monoclonal antibody, was deployed in DESTINY-Breast04, a landmark phase III trial that has paved the way for redefining a sizeable subset of patients with HER2-negative disease as having HER2-low tumors. It is the first approved companion diagnostic for assessing HER2-low status in breast cancer.
  • Monica Bertagnolli, MD, started her tenure as the NCI's 16th director—the first woman to hold this position. A surgical oncologist and highly regarded researcher, she championed integrating tumor-specific biomarkers in clinical trial protocols; her studies of APC and inflammation also boosted understanding of how colorectal cancer develops. Now, she aims to lead the agency on probing the biological processes disrupted by cancer, finding and testing new therapies and prevention strategies, as well as partnering with patients to improve care and increase clinical trial participation.
  • Clovis Oncology's rucaparib (Rubraca) extended radiographic progression-free survival (rPFS) in men with metastatic castration-resistant prostate cancer (mCRPC). In the phase III TRITON3 study, among 405 patients who received either the PARP inhibitor or standard therapy (physician's choice) for mCRPC, the median rPFS was 10.2 months versus 6.4 months, respectively, improving to 11.2 months for patients in the rucaparib arm with BRCA-mutant disease. TRITON3 is the confirmatory trial supporting rucaparib's current accelerated approval for BRCA-mutant mCRPC; the data will also be filed next year for a label expansion.
  • Another PARP inhibitor, talazoparib (Talzenna; Pfizer), showed positive top-line results in mCRPC. In the phase III TALAPRO-2 trial, among 1,095 patients given either talazoparib or placebo alongside Pfizer's antiandrogen enzalutamide (Xtandi), the experimental combination induced "a statistically significant and clinically meaningful improvement in rPFS," a company press release noted. There was also a trend toward improved overall survival. Pfizer will submit detailed study findings for presentation at a future medical meeting and share the data with global regulatory authorities.
  • Cue Biopharma's CUE-101 was fast-tracked for evaluation in human papilloma virus–associated (HPV16+) recurrent/metastatic head and neck squamous cell carcinoma. An off-the-shelf treatment, CUE-101 exhibits two signals—the HPV E7 protein and an engineered IL2 variant—aimed at triggering and expanding tumor-specific T-cell activity. It is being assessed in a phase I trial as monotherapy and in combination with pembrolizumab (Keytruda; Merck).

September 2022

September 23–29

  • Congress is set to pass a bill authorizing the FDA to collect user fees from companies that produce certain drugs and biologic products to help fund the timely review of applications for approval. The Prescription Drug User Fee Act must be reauthorized every 5 years; legislation providing for user fees was last passed in 2017, and that authorization will end at midnight on September 30.
  • By an 8–4 vote, the FDA's Oncologic Drugs Advisory Committee (ODAC) recommended against approving duvelisib (Copiktra; Secura Bio) for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma, saying that the PI3K inhibitor lacks a favorable risk–benefit profile. Reviewing 5-year overall survival (OS) data from the DUO trial, FDA staff noted an increased risk of death and greater toxicity with duvelisib compared with ofatumumab (Arzerra; Novartis). However, Secura Bio representatives pointed to a significant difference in crossover from the ofatumumab arm to the duvelisib arm as a confounding factor. The FDA needn't follow ODAC's advice, but it usually does so.
  • The ODAC also recommended against approving melphalan flufenamide (melflufen; Pepaxto; Oncopeptides) by a 14–2 vote, saying that the risks outweigh its possible benefits for patients with multiple myeloma. The drug was granted accelerated approval in February 2021, but a phase III confirmatory trial found that OS was shorter among patients who received the drug than those who received a control regimen, prompting Oncopeptides to voluntarily remove the drug from the market in October 2021. However, the company rescinded its voluntary withdrawal in January to work with the FDA to interpret the most recent data with the hope of a new approval.
  • Researchers reported that in 17 patients with refractory multiple myeloma, a chimeric antigen receptor (CAR) T-cell therapy targeted to a G protein–coupled receptor, GPRC5D, yielded a response in 12 of them (N Engl J Med 2022;387:1196–206); six patients had a complete response. The patients had received a median of six multiple therapies before enrolling in the phase I trial, including several who had received CAR T cells targeting BCMA. The trial was inspired by preclinical research showing that, compared with normal cells, GPRC5D was particularly abundant on myeloma cells.
  • The NIH announced that it will launch a program to systematically investigate the function of every human gene and generate a catalog of the molecular and cellular consequences of inactivating each gene. According to the NIH, projects funded by the program will use null alleles, "versions of genes that do not make functional proteins… In the absence of making its functional protein, a given gene's function can be more readily deduced by studying the resulting biological characteristics, or phenotype." The Molecular Phenotypes of Null Alleles in Cells (MorPhiC) program will initially be funded for 5 years at a total of $42.5 million pending availability of funds.
  • The breast cancer organization Susan G. Komen announced the expansion of its screening and diagnostics program from nine cities to 12. Income-eligible residents in Dallas, TX, Los Angeles, CA, and Memphis, TN, can now access breast cancer screening and diagnostic services at no cost. The program has already been operating in Atlanta, GA; Fort Worth, TX; Houston, TX; Madison, WI; Marshfield, WI; Philadelphia, PA; Virginia Beach, VA; and Washington, DC.

September 16–22

  • The FDA granted accelerated approval to selpercatinib (Retevmo; Eli Lilly) to treat adults with locally advanced or metastatic solid tumors with a RET gene fusion whose cancer has advanced on or after a systemic treatment or who have no other satisfactory therapeutic options. Data from the LIBRETTO-001 trial showed that selpercatinib yielded clinically meaningful and durable responses across a variety of tumor types, including pancreatic and colon cancers, in patients with RET-driven malignancies. The agency also granted regular approval to selpercatinib for the treatment of adults with locally advanced or metastatic non–small cell lung cancer (NSCLC) with a RET gene fusion; the drug had received accelerated approval for this indication in 2020.
  • By a 9–4 vote, an FDA advisory committee decided that the possible benefits of poziotinib do not outweigh the risks for patients with NSCLC with HER2 exon 20 insertion mutations, MedPage Today reported. The committee said that the Spectrum Pharmaceuticals drug, a tyrosine kinase inhibitor, did not demonstrate a major improvement over other treatment options and produced high rates of toxicity that required dose interruptions or reductions; it also said that Spectrum didn't sufficiently examine various doses, a claim that the company denied. When considering drugs for approval, the FDA need not follow its advisory committee's advice but it usually does so.
  • Fennec Pharmaceuticals announced that the FDA approved sodium thiosulfate (Pedmark) to reduce the risk of hearing loss associated with cisplatin in children aged 1 month or older with localized non-metastatic solid tumors. The approval was based on safety and efficacy data from two pivotal randomized phase III trials that compared sodium thiosulfate plus cisplatin with cisplatin alone. In both studies, the incidence of hearing loss was significantly lower in the sodium thiosulfate arm.
  • The American Association for Cancer Research (AACR) released its 12th annual Cancer Progress Report, which provides "up-to-date cancer incidence, mortality, and survivorship statistics and discusses the latest research in cancer etiology, biology, early detection, diagnosis, treatment, and prevention, including the use of artificial intelligence (AI)-based early detection systems and liquid biopsies that are moving rapidly to the clinic" (https://cancerprogressreport.aacr.org). It also makes policy recommendations to make sure that the United States "maintains its momentum against cancer."
  • The AACR celebrated its 115th anniversary. At a gala event in Washington, DC, the nonprofit also bestowed awards on numerous individuals and organizations for their outstanding efforts to advance cancer research.

Additional news from September 9–15:

  • On the 60th anniversary of President John F. Kennedy's "Moonshot" speech, President Joe Biden outlined several research advances against cancer that have occurred as part of his reinvigorated Cancer Moonshot effort. Among them: an executive order to establish the Biotechnology and Biomanufacturing Initiative to ensure that cutting-edge technologies and other innovations are developed and manufactured in the United States, a cap on out-of-pocket prescription drug costs for Medicare beneficiaries that could save patients with cancer thousands of dollars a year, and the launch of a large national trial to identify and develop blood tests to detect cancer.
  • Biden appointed Renee Wegrzyn, PhD, as the first director of the Advanced Research Projects Agency for Health (ARPA-H), which was created in 2020 to drive biomedical innovation and medical research to "prevent, detect, and treat some of the most intractable diseases, including cancer," according to a White House press release. Wegrzyn is currently a vice president of business development at Ginkgo Bioworks and head of innovation at Concentric by Ginkgo. She previously served as program manager in the Biotechnologies Office of the Defense Advanced Research Projects Agency, one of the institutions that inspired the creation of ARPA-H.
  • The Oversight Committee of the Cancer Prevention and Research Institute of Texas (CPRIT) approved $49 million in research grants to support core facilities, access to clinical trials, computational oncology, drug discovery, and childhood cancer research. CPRIT, created and approved by voters in the state in 2007, is the largest state funder of cancer research and the second largest source of public funding for cancer research in the world.

September 9–15

This week: Special coverage of the ESMO 2022 Congress, as well as other news.

  • According to updated findings from the phase III TROPiCS-02 trial presented at the ESMO 2022 Congress in Paris, France, Gilead's sacituzumab govitecan (Trodelvy) significantly extended overall survival (OS) by 3.2 months compared with physician's choice of chemotherapy in patients with metastatic hormone receptor (HR)–positive/HER2-negative breast cancer who had already received several other types of therapies, including endocrine therapy, a CDK4/6 inhibitor, and chemotherapies. At the 2022 American Society of Clinical Oncology meeting in June, OS favored sacituzumab by 1.6 months, which was not statistically significant. A TROP2-targeting antibody–drug conjugate, sacituzumab govitecan is FDA approved for the treatment of triple-negative breast cancer.
  • Also at the ESMO meeting, researchers working on the phase III MONARCH 3 trial reported that OS for patients receiving abemaciclib (Verzenio; Lilly) and a nonsteroidal aromatase inhibitor (NSAI) is trending longer in patients with advanced HR-positive/HER2-negative breast cancer than in those receiving a placebo and NSAI—67.1 months vs. 54.5 months, respectively—but that difference has not yet reached statistical significance. However, "the data are maturing favorably," said lead author Matthew Goetz, MD, of the Mayo Clinic in Rochester, MN. The CDK4/6 inhibitor–NSAI combination has already been approved as an initial therapy for postmenopausal patients with this form of breast cancer based on trial data showing improved progression-free survival (PFS).
  • In an international phase II clinical trial, 63.3% of 79 patients with stage II–IV cutaneous squamous cell carcinoma had their tumors nearly or completely eradicated with neoadjuvant cemiplimab (Libtayo; Regeneron/Sanofi); results were simultaneously published (N Engl J Med 2022 Sep 12 [Epub ahead of print]). Treatment with the PD-1 inhibitor followed by surgery yielded a pathologic complete response rate of 50.6%; another 12.7% of patients experienced a major pathologic response. Study presenter Neil Gross, MD, of The University of Texas MD Anderson Cancer Center in Houston was quoted as saying that "if you can avoid radiation or have a smaller surgery, and you can keep your eye, ear, or nose, that's a huge win for people. That's the excitement of this approach: the chance to make life so much better for our patients in the future."
  • Updated results of two phase III trials reported at ESMO—PAOLA-1 and SOLO-1—demonstrated clinically meaningful improved OS in patients with advanced ovarian cancer who took olaparib (Lynparza; AstraZeneca), a PARP inhibitor, with or without bevacizumab. After 5 years of follow-up in PAOLA-1, the combination increased median OS to 56.5 months versus 51.6 months with bevacizumab alone in newly diagnosed patients. The SOLO-1 trial, results of which were also published, demonstrated that 67% of patients with advanced disease and BRCA mutations treated with maintenance olaparib were alive after 7 years vs. 47% of those taking a placebo (J Clin Oncol 2022 Sep 9 [Epub ahead of print]).
  • In the first phase III trial of a KRASG12C inhibitor in patients with non–small cell lung cancer and the KRASG12C mutation, those who took sotorasib (Lumakras; Amgen) showed superior PFS and a greater overall response rate (ORR). In the CodeBreak 200 study, after 12 months, the PFS rate was 24.8% with sotorasib and 10.1% with docetaxel; the ORRs were 28.1% and 13.2%. However, the patients did not experience any improvement in OS, perhaps because the study wasn't powered to assess OS and many patients in the docetaxel arm crossed over to the sotorasib arm, researchers reported at ESMO.
  • Three trials of checkpoint inhibitors failed to show much benefit for patients taking the drugs as an adjuvant treatment for high-risk renal cell carcinoma. In the CheckMate 914 trial, the median disease-free survival (DFS) was not reached with the PD-1 inhibitor nivolumab (Opdivo; Bristol Myers Squibb) plus the CTLA4 inhibitor ipilimumab (Yervoy) compared with 50.7 months with placebo after a median follow-up of 37 months. In the PROSPER trial, after a median follow-up of 16 months, perioperative nivolumab did not improve recurrence-free survival compared with surgery alone. And in the IMmotion010 trial, after a median follow-up of 44.7 months, the median DFS was 57.2 months with adjuvant atezolizumab (Tecentriq; Genentech), a PD-L1 inhibitor, compared with 49.5 months with placebo (Lancet 2022 Sep 10 [Epub ahead of print]).
  • Initial results from the NICHE-2 study, reported at ESMO, showed that a few weeks of neoadjuvant nivolumab plus ipilimumab led to pathologic responses in 99% of 107 patients with nonmetastatic mismatch repair–deficient colon cancer; 95% experienced major pathologic responses, and 67% experienced pathologic complete responses. The findings, presented by Myriam Chalabi, MD, of the Netherlands Cancer Institute in Amsterdam, prompted sustained applause from meeting attendees. "You don't see many waterfall plots like this—it's striking data," said discussant James Larkin, MD, PhD, of The Royal Marsden Hospital in London, UK.

In other news:

  • A gift of $55 million will establish the Basser Cancer Interception Institute at the University of Pennsylvania Abramson Cancer Center in Philadelphia. The institute, which will be part of the Basser Center for BRCA, will aim to "intercept" cancer when the first abnormal BRCA1/2 cells develop—or perhaps even before that—through the development of drugs and immune-based therapies, new methods of detecting cancer cells with biomarkers, and artificial intelligence. The funds were donated by university alumni Mindy and Jon Gray.

September 2–8

  • The FDA approved durvalumab (Imfinzi) plus gemcitabine and cisplatin for adults with certain biliary tract cancers (BTC), AstraZeneca reported. The decision was based on data from the phase III TOPAZ-1 trial, in which 685 patients with histologically confirmed locally advanced inoperable or metastatic BTC who had not already received systemic therapy for advanced disease received all three drugs or a placebo plus gemcitabine and cisplatin. Median overall survival was 12.8 months and 11.5 months in the durvalumab and placebo arms, respectively; the median progression-free survival was 7.2 months and 5.7 months, respectively.
  • The European Commission blocked Illumina's $8 billion acquisition of GRAIL, which the companies announced in 2020. The deal "would have enabled and incentivized Illumina to foreclose GRAIL's rivals, who are dependent on Illumina's technology, from access to an essential input they need to develop and market their own tests." However, in the United States, a judge ruled in favor of Illumina over the Federal Trade Commission. Biotech giant Illumina makes next-generation sequencing systems for genomic analyses; GRAIL is developing blood tests to aid early cancer detection.
  • With the incidence of early-onset cancers having risen dramatically since about 1990, researchers conducted extensive analyses of available data to understand why. They found that the risk of cancer is increasing with each generation and that the early life exposome—which includes one's diet, lifestyle, weight, environmental exposures, and microbiome—has changed substantially in the last several decades (Nat Rev Clin Oncol 2022 Sep 6 [Epub ahead of print]). Although the researchers acknowledged that the increased incidence could be due in part to earlier detection through screening programs, they also noted that several of the cancers on the rise are tied to the digestive system and that the consumption of highly processed foods, sugary beverages, and alcohol, as well as obesity and a sedentary lifestyle, directly affects the microbiome.
  • The FDA approved Fresenius Kabi's pegfilgrastim biosimilar Stimufend for use in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia. A biosimilar of Amgen's Neulasta, Stimufend is a leukocyte growth factor designed to decrease the incidence of infection, a common and life-threatening risk in patients receiving myelosuppressive chemotherapy. Earlier this year, the company received the European Commission's blessing to market Stimufend in Europe.
  • Roche announced it will acquire Good Therapeutics for $250 million, as well as additional payments based on reaching certain development, regulatory, and commercial milestones. With the acquisition, Roche will gain Good Therapeutics' PD-1–regulated IL2 program and an exclusive right to the platform technology for the development of PD-1–regulated IL2 receptor agonist therapeutics. Such conditionally active agents should avoid systemic immune activation because the molecules are context-dependent and become active only when an antibody sensor has bound its target.

August 2022

August 26–September 1

  • The phase III CodeBreaK 200 trial evaluating sotorasib (Lumakras; Amgen) met its primary endpoint of progression-free survival (PFS), demonstrating superiority over standard-of-care docetaxel chemotherapy in 345 patients with KRASG12C-mutated non–small cell lung cancer (NSCLC). All of the patients had previously received platinum-based doublet chemotherapy and a checkpoint inhibitor. Detailed data will be presented during the ESMO Congress 2022, which will be held in Paris, France, September 9–13.
  • Incyte announced that the FDA approved pemigatinib (Pemazyre) to treat adults with relapsed/refractory myeloid/lymphoid neoplasms (MLN) with FGFR1 rearrangement, a rare condition. The approval was based on data from the phase II FIGHT-203 study, in which 28 patients with MLN who experienced disease relapse after an allogeneic hematopoietic stem cell transplant or disease-modifying treatment, or who were ineligible for these therapies, received pemigatinib; 22 of them (79%) experienced a complete cytogenetic response. Pemigatinib was approved in 2020 for adults with certain cholangiocarcinomas with an FGFR2 fusion or other rearrangement.
  • The European Commission approved asciminib (Scemblix) to treat adults with Philadelphia chromosome–positive chronic myeloid leukemia (CML) in chronic phase previously treated with at least two tyrosine kinase inhibitors (TKI), Novartis announced. The approval is based on results from the pivotal phase III ASCEMBL trial, in which patients who received asciminib had nearly twice the rate of major molecular response as those who received the TKI bosutinib (Bosulif; Pfizer)—25.5% vs. 13.2%, respectively—with a significantly lower rate of discontinuation due to adverse reactions—5.8% vs. 21.1%, respectively. Unlike oral TKI therapies for CML, asciminib targets the ABL myristoyl pocket.
  • Jounce Therapeutics announced that it will reevaluate development of vopratelimab, an ICOS agonist, following disappointing results in the phase II SELECT trial. In the trial, 69 patients with NSCLC—who had already received one treatment regimen, were naïve to immunotherapy, and were selected based on an 18-gene RNA tumor inflammation signature predicting the emergence of ICOShi CD4+ T cells—received vopratelimab plus the company's PD-1 inhibitor pimivalimab or pimivalimab alone. Although researchers noted an improvement in PFS and overall survival, the level of efficacy was too low to justify the launch of a late-stage trial.
  • The FDA gave Curis the green light to resume enrolling patients in the monotherapy phase of the TakeAim Leukemia study, which is investigating the use of emavusertib, an IRAK4 inhibitor. IRAK4 plays an essential role in the toll-like receptor and IL1 receptor signaling pathways. The FDA placed a partial clinical hold on the trial in April due to concerns about the identification and management of rhabdomyolysis.

August 19–25

  • Pharmacyclics' ibrutinib (Imbruvica) received FDA approval for children and young adults, ages 1 to 22, with chronic graft-versus-host disease after at least one systemic therapy. Efficacy was evaluated in iMAGINE, an open-label, multicenter, single-arm trial of the drug in 47 patients, with overall response rate (ORR) through week 25 as the main efficacy measure. The ORR was 60%, and the median duration of response was 5.3 months; the most common adverse reactions were anemia, musculoskeletal pain, and fever.
  • The European Commission granted conditional marketing authorization for teclistamab (Tecvayli; Janssen/Johnson & Johnson), a single-agent treatment for adults with relapsed/refractory multiple myeloma. Patients must have received at least three other therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody. The approval is the first for teclistamab, a first-in-class, off-the-shelf bispecific antibody that directs CD3-positive T cells to kill BCMA-expressing myeloma cells.
  • The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 found that nearly 45% of cancer deaths are caused by risk factors such as smoking, drinking alcohol, and high body mass index (Lancet 2022;400:563–91). Between 2010 and 2019, cancer deaths attributed to modifiable risk factors increased by 20%. Study researchers emphasized that prevention efforts should focus heavily on such risk factors to decrease cancer mortality—and to lessen the burden of cancer-related health problems.
  • In the United States and Europe, most drugs receiving an accelerated approval don't provide "high added therapeutic value," according to an analysis of speedy OKs from 2007 through 2021 (JAMA Health Forum 2022;3:e222685). In the United States, 146 drug indications (both new and supplemental) received accelerated approval; in Europe, 58 indications (all first indications) were given conditional marketing approval, a pathway similar to the FDA's accelerated approval. Overall, 38.9% of such approvals in the United States and 37.5% of them in the European Union were deemed to have high added therapeutic value; the rates were lower for cancer indications—36% and 30.8%, respectively.
  • Foghorn Therapeutics announced that the FDA has placed a full clinical hold on a phase I dose-escalation study of FHD-286, which inhibits BRG1 and BRM, in relapsed/refractory acute myelogenous leukemia and myelodysplastic syndrome; the full clinical hold is due to reports of additional suspected cases of fatal differentiation syndrome since a partial hold was implemented. BRG1 and BRM play a role in the chromatin regulatory system. The phase I dose-escalation study of FHD-286 in metastatic uveal melanoma is continuing.

August 12–18

  • During the August session of the American Society of Clinical Oncology's Plenary Series, researchers reported that, in a retrospective analysis of germline DNA sequencing on 7,788 patients with lung cancer, almost 15% had pathogenic germline variants (PGV) that put them—and their family members—at greater risk for other cancers. Of those patients, about 95% had a PGV that could be addressed with an FDA-approved drug or a drug under investigation in a clinical trial. In addition, the researchers noted that in more than 61% of cases, the PGV was in genes associated with DNA damage repair or homologous recombination repair.
  • The NCI announced it will award $23 million to establish four centers to study telehealth and the role it can play in cancer prevention, screening, diagnosis, treatment, and survivorship. In addition to developing ways to use telehealth in cancer care, the centers will identify and address "telehealth-related disparities among vulnerable populations, including racial and ethnic groups, rural residents, older adults, people who are uninsured or low-income, people who are socially isolated, and people who have limited digital literacy." The four centers will be led by the NYU Grossman School of Medicine in New York, NY; Northwestern University in Evanston, IL; the University of Pennsylvania in Philadelphia; and Memorial Sloan Kettering Cancer Center, also in New York.
  • Based on disappointing results of an interim analysis of its phase III AMEERA-5 study, Sanofi will end development of amcenestrant, an investigational oral selective estrogen receptor (ER) degrader. In patients with ER-positive, HER2-negative advanced breast cancer, amcenestrant plus palbociclib, a CDK4/6 inhibitor (Ibrance; Pfizer) "did not meet the prespecified boundary for continuation in comparison with the control arm," in which patients received the aromatase inhibitor letrozole plus palbociclib. All other studies of amcenestrant, including in early-stage disease (AMEERA-6), will also be discontinued.
  • A review by the Office of the Inspector General found that the NIH does not take adequate steps to ensure that clinical trial results are reported in accordance with federal requirements, takes little action against those who do not comply with the requirements, and continues to fund research by those who have not submitted clinical trial results (see https://oig.hhs.gov/oas/reports/region6/62107000.asp). The review called for the agency to improve its procedures, increase enforcement of regulations, and work with those who receive money to support clinical trials to understand and address challenges related to submitting results to ClinicalTrials.gov.
  • An arbitrator ruled in favor of Daiichi Sankyo in a patent dispute with Seagen. Seagen had claimed certain intellectual property rights related to the Japanese company's antibody–drug conjugate trastuzumab deruxtecan (Enhertu) based on a collaboration agreement between the companies from 2008 to 2015. However, the arbitrator disagreed with Seagen's interpretation of the contract and cited the statute of limitations in making the decision.
  • The European Commission greenlighted Celltrion Healthcare's bevacizumab biosimiliar, Vegzelma (CT-P16), which references Avastin (Genentech). The drug is approved for the treatment of metastatic breast cancer, non–small cell lung cancer, advanced/metastatic renal cell cancer, metastatic carcinoma of the colon or rectum, ovarian cancer, and cervical cancer. FDA approval for the drug is anticipated by the end of September, according to Celltrion.

August 5–11

  • Daiichi Sankyo announced that the FDA granted accelerated approval to trastuzumab deruxtecan (Enhertu) to treat adults with inoperable or metastatic non–small cell lung cancer (NSCLC) whose tumors have HER2 mutations and who have already received a systemic therapy. The decision was based on the DESTINY-Lung02 trial, in which the confirmed overall response rate (ORR) was 58% and the median duration of response (DOR) was 8.7 months among 52 patients. The agency also approved Life Technologies' Oncomine Dx Target Test and Guardant Health's Guardant360 CDx as companion diagnostics.
  • The agency also greenlighted a drug combination to treat metastatic hormone-sensitive prostate cancer—darolutamide (Nubeqa; Bayer HealthCare) tablets with the chemotherapeutic docetaxel. Efficacy of the combination was based on the randomized, multicenter, double-blind, placebo-controlled ARASENS trial, which included 1,306 men. Median overall survival was not reached in the darolutamide/docetaxel arm and was 48.9 months in the docetaxel monotherapy arm, and the drug duo also significantly delayed increases in pain.
  • Additionally, the FDA granted regular approval to capmatinib (Tabrecta; Novartis) for adults with metastatic NSCLC whose tumors have a mutation leading to MET exon 14 skipping, as detected by an FDA-approved test. The decision was based on new and longer-term data from the GEOMETRY mono-1 trial: Among 60 treatment-naïve patients, the ORR was 68% and the DOR was 16.6 months, and among 100 previously treated patients, the ORR was 44% and the DOR was 9.7 months. Accelerated approval for the same indication had been granted in May 2020.
  • Over the past two decades, response rates to agents in phase I trials almost doubled without a concomitant increase in treatment-related deaths, researchers reported (Lancet 2022;400:512–21). However, they found "significant heterogeneity in overall response by various factors, such as cancer type, investigational agent, and trial design." The upshot: Although "modern" phase I studies have yielded promising results in the treatment of solid tumors, people staffing clinical trials must still ensure that patients are making informed decisions regarding trial participation.
  • Talc-based Johnson's Baby Powder will be discontinued worldwide next year, according to maker Johnson & Johnson; the company stopped selling the product in the United States and Canada in 2020. Although the company has repeatedly said that the talc-based product does not contain asbestos and does not cause cancer, it markets a cornstarch-based formulation in countries around the world. Countless lawsuits related to talc that significantly harmed the company's bottom line drove the decision.

July 29–August 4

  • Breaking: On August 5, the FDA approved trastuzumab deruxtecan, or T-DXd, (Enhertu) for adults with inoperable or metastatic HER2-low breast cancer who have previously received a chemotherapy for metastatic disease or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy. The decision was based on the DESTINY-Breast04 trial, which examined the Daiichi Sankyo antibody–drug conjugate in 557 adults with the disease; study data were published in June (N Engl J Med 2022;387:9–20). In the overall trial population, median overall survival was 23.4 months in the T-DXd arm and 16.8 months in the chemotherapy arm.
  • The Society for Immunotherapy of Cancer (SITC) published a clinical practice guideline on immunotherapy for the treatment of nonmelanoma skin cancer (J Immunother Cancer 2022;10:e004434). According to the organization, the guideline "assists clinicians on how to navigate through the sometimes challenging issues that arise during routine use of [immune checkpoint inhibitors], including treatment selection, immunosuppressed patient populations, toxicity management, assessment of atypical responses, and quality of life and survivorship concerns."
  • Merck announced that the KEYNOTE-921 trial testing pembrolizumab (Keytruda) in combination with chemotherapy did not meet its primary endpoints of overall survival (OS) and radiographic progression-free survival (PFS) in men with metastatic castration-resistant prostate cancer compared with chemotherapy alone. Although there were trends in favor of both OS and radiographic PFS in patients who received the drug duo, "the results did not meet statistical significance per the prespecified statistical plan." Pembrolizumab is a PD-1 checkpoint inhibitor.
  • Merck also announced that, for patients with liver cancer, pembrolizumab did not meet a study's primary endpoints when combined with lenvatinib, a VEGFR1/2/3 inhibitor discovered by Eisai. The phase III LEAP-002 trial compared the combination with lenvatinib alone as a first-line treatment for patients with inoperable hepatocellular carcinoma. Although there were trends in favor of the pair, once again, "the results did not meet statistical significance per the prespecified statistical plan." The FDA has approved the combination for the treatment of certain patients with endometrial or renal cell carcinomas.
  • The European Union approved olaparib (Lynparza) for patients with germline BRCA-mutated HER2-negative high-risk early breast cancer—as adjuvant monotherapy or with endocrine therapy—who've already been treated with chemotherapy. The approval of the AstraZeneca/Merck drug was based on the phase III OlympiA trial, which found that olaparib demonstrated significant and clinically meaningful invasive disease-free survival, reducing the risk of breast cancer recurrence, new cancers, or death by 42% versus placebo; there was also improvement in OS, reducing the risk of death by 32% versus placebo (N Engl J Med 2021;384:2394–405).
  • A panel of federal judges upheld the short jail sentence for former GSK researcher Yu Xue, who admitted to stealing trade secrets related to cancer drugs for a company she cofounded in China, Renopharma. According to the Third U.S. Circuit Court of Appeals decision, because Xue, with her co-conspirator Tao Li, did not intend to "inflict a pecuniary harm on the victim, GSK," and GSK didn't suffer any financial loss, Xue's original sentence will not be "enhanced." Xue had been sentenced to 8 months in prison and Li to 59 days, which they have served; government prosecutors had sought 10 years and 7 years, respectively.
  • The FDA approved a new tablet formulation of acalabrutinib (Calquence) for all current indications in adults, including chronic lymphocytic leukemia and small lymphocytic lymphoma, as well as patients with relapsed/refractory mantle cell lymphoma. The tablet offers equivalent efficacy, safety, and consistent dosing compared with the current capsule, and it enables acalabrutinib to be taken with a proton pump inhibitor for the treatment of acid reflux and peptic ulcers.
  • Charlottesville's University of Virginia Cancer Center received more than $5.75 million from an anonymous donor to speed the development of treatments for rare blood cancers, such as large granular lymphocytic leukemia, and aid patients with these cancers in accessing clinical trials of investigational drugs.

July 2022

July 22–28

  • Researchers reported that frequent aspirin use is linked to lower risk of ovarian cancer in women with risk factors for the disease—BRCA mutations, family history of breast or ovarian cancer, endometriosis, obesity, having had children, oral contraceptive use, and tubal ligation (J Clin Oncol 2022 Jul 22 [Epub ahead of print]). Combined data from 17 studies found that among these women, taking aspirin at least 6 days a week reduced ovarian cancer risk by 13% overall; women with two or more risk factors experienced a 19% reduction. Risk reductions were associated with all risk factors except endometriosis.
  • Based on findings from a multicenter study, patients with early-stage Hodgkin lymphoma are more likely to die from cardiovascular disease (CVD) than cancer (Cancer 2022 Jul 25 [Epub ahead of print]). The study included 15,889 people in the United States who were diagnosed with the disease between 1983 and 2015. Researchers noted that the risk of dying from classic Hodgkin lymphoma dropped dramatically in the past few decades, but the risk of dying from CVD among these patients has declined slowly or remained static. The analysis also found that patients with this form of lymphoma had a higher risk of dying from CVD than the general population at nearly all time points.
  • Seagen and Astellas Pharma announced top-line data results from Cohort K of the phase Ib/II EV-103/KEYNOTE-869 trial assessing a drug combination to treat patients with inoperable locally advanced or metastatic urothelial cancer who cannot take cisplatin-based chemotherapy: 64.5% of the participants, who received enfortumab vedotin (Padcev) and pembrolizumab (Keytruda; Merck) as their first therapy for urothelial cancer, responded to it; the median duration of response was not reached. Pembrolizumab is a PD-1 inhibitor; enfortumab vedotin is a first-in-class antibody–drug conjugate directed against Nectin-4.
  • [The prior statement regarding DCVax-L, published May 13, has been removed. An updated version of the statement appears below.]

    Since the first announcement of the DCVax-L Phase 3 glioblastoma (GBM) trial results presented by Dr. Paul Mulholland on May 10, 2022, at the New York Academy of Sciences (NYAS) Conference on Frontiers in Cancer Immunotherapy, Northwest Biotherapeutics ("Company") has indicated that our prior statement did not include certain information contained in the presentation, including the updated primary and secondary endpoints of the trial.

    The Company believes the presentation shows that DCVax-L-treated patients, when compared to external controls, exhibited a clinically meaningful and statistically significant extension of survival in both newly diagnosed and recurrent GBM, which are the two updated endpoints of the trial. For details regarding the full presentation at NYAS, please see the following: https://virtualtrials.org/dcvax/dcvax.pdf.
  • The National Comprehensive Cancer Network (NCCN) issued new patient guidelines for breast cancer screening and diagnosis that emphasize annual mammograms for all women over 40 at average risk for the disease (available at https://www.nccn.org/patientguidelines). The guidelines are designed to help people understand their personal risk for breast cancer, when they should begin screening, and how often they should be screened to detect cancer earlier, when they'll have more treatment options and better outcomes. The information may help patients have more informed conversations with health care providers.
  • The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) recommended against the use of rucaparib (Rubraca; Clovis Oncology) as monotherapy to treat patients with platinum-sensitive, recurrent BRCA-mutated high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who have had at least two platinum-based chemotherapy regimens but cannot tolerate more. The CHMP recommendation is based on final overall survival data from the ARIEL4 study, which found that patients treated with the PARP inhibitor lived 19.4 months on average compared with 25.4 months for those who received chemotherapy. Clovis voluntarily pulled the drug for this indication in the United States in May.
  • In a report published by the National Academies of Sciences, Engineering, and Medicine, environmental health experts call for blood tests to check levels of per- and polyfluoroalkyl substances (PFAS), with regular monitoring and screening for health problems if PFAS levels are high (available at http://nationalacademies.org). These "forever chemicals" have been linked to kidney and testicular cancers, as well as other medical conditions. PFAS are used in nonstick pans, water-repellent fabrics, fire-fighting foam, and other products and "can leak into the environment where they are made, used, disposed of, or spilled."

July 15–21

  • Merck announced that the phase III LYNK-003 trial evaluating olaparib (Lynparza) for inoperable or metastatic colorectal cancer will stop for futility based on an interim analysis of the data by an independent committee. Researchers had been investigating olaparib with or without bevacizumab for the treatment of patients with the condition whose disease had not advanced following first-line induction. The PARP inhibitor, which is being developed in collaboration with AstraZeneca, will continue to be studied as a monotherapy and in combination with other drugs for the treatment of metastatic prostate cancer, ovarian cancer, breast cancer, and pancreatic cancer.
  • In addition, Merck said that the KEYNOTE-412 trial of pembrolizumab (Keytruda) with concurrent chemoradiation therapy (CRT) followed by pembrolizumab maintenance therapy did not meet its primary endpoint of event-free survival (EFS) for the treatment of patients with inoperable locally advanced head and neck squamous cell carcinoma (HNSCC); although there was an improvement in EFS in these patients compared with placebo plus CRT in the phase III study, it was not statistically significant. The PD-1 inhibitor is approved as a monotherapy and in combination regimens for certain patients for HNSCC in the United States, Europe, China, Japan, and other countries.
  • In April, a jury for the U.S. District Court for the Eastern District of Texas found that Daiichi Sankyo's antibody–drug conjugate targeting HER2, trastuzumab deruxtecan (T-DXd; Enhertu), infringes on a Seagen patent and awarded Seagen $41.8 million in damages. Although the jury found that the infringement was willful, the court decided this week that increasing that amount wasn't warranted; the Japanese company said it "will continue to vigorously defend its rights" and "contest the judgment and damages awarded to Seagen." AstraZeneca has partnered with Daiichi Sankyo to develop and commercialize T-DXd.
  • Daiichi Sankyo and AstraZeneca did receive some good news: The European Union approved T-DXd as a monotherapy to treat patients with inoperable or metastatic HER2-positive breast cancer who have already received at least one anti-HER2 regimen. The decision was based on the phase III DESTINY-Breast03 trial, which found that the antibody–drug conjugate reduced the risk of disease progression or death by 72% compared with trastuzumab emtansine (Kadcyla; Genentech; N Engl J Med 2022;386:1143–54). The FDA granted accelerated approval to the drug in late 2019 and regular approval in May.
  • The European Commission also granted full marketing authorization for selinexor (Nexpovio; Karyopharm/Menarini) in combination with once-weekly bortezomib (Velcade; Takeda) and dexamethasone to treat adults with multiple myeloma who have already received at least one other therapy. The decision was based on results of the phase III BOSTON trial, which demonstrated that the regimen resulted in a statistically significant reduction in the risk of disease progression or death compared with standard twice-weekly bortezomib plus dexamethasone (Lancet 2020;396:1563–73). Selinexor is a first-in-class XPO1 inhibitor.
  • Novartis will not seek FDA approval for tislelizumab as a monotherapy for non–small cell lung cancer, the company announced. Instead, the company, in partnership with BeiGene, will focus on getting the go-ahead to market the PD-1 inhibitor for the treatment of esophageal cancer. That decision was put on hold last week because U.S. regulators couldn't visit China to conduct inspections due to COVID-19 travel restrictions.
  • VBL Therapeutics announced that the phase III OVAL trial of ofra-vec (ofranergene obadenovec; VB-111) in platinum-resistant ovarian cancer did not meet its primary endpoints—statistically significant improvements in progression-free survival (PFS) or overall survival (OS). Patients who were randomly assigned to receive a combination of ofra-vec and paclitaxel had a median PFS of 5.3 months versus 5.7 months in the paclitaxel control arm; in an interim analysis, the median OS was 13.4 months and 13.1 months, respectively. Ofra-vec is designed to combine the blockade of tumor microvasculature with an antitumor response.

July 8–14

  • Pfizer announced that the FDA approved crizotinib (Xalkori) for people age 1 and older with inflammatory ALK-positive myofibroblastic tumors (IMT) that are in operable, recurrent, or refractory to other treatments. In a trial involving 14 children with IMT, the objective response rate was 86%; in a second trial, which included seven adults with IMT, five (71%) had an objective response. Crizotinib is also approved to treat ALK-positive and ROS1-positive metastatic non–small cell lung cancer.
  • Merck will pay Finland's Orion $290 million to jointly develop and market ODM-208, a steroid synthesis inhibitor, as well as follow-up compounds in the same class. ODM-208 targets cytochrome P450 11A1, also known as CYP11A1, which plays a role in producing steroids from cholesterol, including androgens that can stimulate the growth of prostate cancer. The agent is currently under investigation in a phase II trial involving patients with metastatic castration-resistant prostate cancer.
  • The FDA has "deferred action" on tislelizumab (BeiGene/Novartis) as a second treatment for patients with inoperable or metastatic esophageal squamous cell carcinoma because agency staff has been unable to conduct necessary inspections in China due to COVID-19–related travel restrictions. The drug's application remains under review, but no timeline for a decision was provided. A humanized IgG4 anti–PD-1 antibody, tislelizumab is designed to minimize binding to Fcγ on macrophages, helping immune cells detect and fight tumors.
  • The National Comprehensive Cancer Network published new guidelines for treating children with brain cancer, underscoring the importance of broad molecular profiling in diagnosing, treating, and identifying clinical trials for patients (accessible at http://www.nccn.org). The guidelines specifically address histopathologic, immunohistochemistry, and molecular assessments for children with high-grade gliomas, recognizing that "the underlying molecular alterations in pediatric gliomas are distinct from those seen in adults." Due to the number of genes of interest and the types of potential recurrent alterations, the guidelines recommend a multimarker, rather than a single-gene, testing strategy.
  • President Joe Biden chose three new members for the President's Cancer Panel, a group of volunteers who advise the president on how to use the resources of the federal government, particularly through the cancer research program, to make progress for people facing a cancer diagnosis and to reduce the burden of cancer on the American population. The new members are Elizabeth Jaffee, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, MD; Mitchel Berger, MD, of the University of California, San Francisco; and Carol Brown, MD, of Memorial Sloan Kettering Cancer Center in New York, NY.

July 1–7

  • The FDA backtracked on its June 23 order calling upon JUUL to stop selling their electronic cigarettes and related products. The agency initially said that JUUL didn't provide "sufficient evidence regarding the toxicological profile of the products" and that some of the company's study findings were concerning "due to insufficient and conflicting data." However, in light of a stay issued by a federal judge the following day, the FDA has now "determined that there are scientific issues unique to the JUUL [marketing] application that warrant additional review" and has temporarily suspended its marketing denial order.
  • In the pivotal phase II MOUNTAINEER trial, Seagen's tucatinib (Tukysa) plus trastuzumab yielded durable responses in patients with previously treated HER2+ metastatic colorectal cancer. After a median follow up of 20.7 months, the objective response rate among 84 patients assigned to receive the combination was 38.1%; the median duration of response was 12.4 months, and the median overall survival was 24.1 months. The company plans to submit the findings, which were presented at the European Society for Medical Oncology World Congress on Gastrointestinal Cancer, to the FDA for approval to treat such patients with tucatinib.
  • AstraZeneca announced that it will acquire TeneoTwo and its CD19/CD3 T-cell engager, TNB-486, for $100 million, but the deal could be worth up to $1.27 billion if certain developmental milestones are met. TNB-486 is under evaluation for relapsed/refractory B-cell non-Hodgkin lymphoma in a phase I trial. AstraZeneca said that the drug, used alone or in combination with a CD20-targeted therapy, could "potentially deepen clinical responses" and improve survival in patients with B-cell malignancies, including diffuse large B-cell lymphoma and follicular lymphoma.
  • In a survey of almost 1,200 patients with cancer and cancer survivors, about 80% said they would be willing to use remote technologies in a clinical trial—for example, providing informed consent online and wearing devices to monitor their condition (JAMA Netw Open 2022;5:e2220053). In addition, patients said they would be more willing to enroll in a trial—even patients who initially said that they wouldn't enroll in a trial—if remote technology would be used to limit travel and the need for in-person appointments.
  • Ohio's Cleveland Clinic announced that a patient successfully received a multi-organ transplant to treat a rare form of appendix cancer, called pseudomyxoma peritonei, that spread to other digestive organs. The 32-year-old man, likely the first ever to undergo such a treatment, was no longer eating and was in hospice at the time of the surgery. Nine months on—with a new liver, stomach, pancreas, and small intestine—he is once again eating, has returned to normal activities, and is free of cancer.

June 2022

June 24–30

  • Bristol Myers Squibb's (BMS) Juno Therapeutics announced that the FDA approved lisocabtagene maraleucel (liso-cel; Breyanzi) for adults with large B-cell lymphoma (LBCL) who don't respond to, or relapse within 12 months of, first-line chemotherapy and are not eligible for hematopoietic stem cell transplantation. The drug's efficacy was evaluated in two trials: In the 184-patient TRANSFORM study, the estimated 1-year event-free survival was 45% in the liso-cel group compared with 24% in the standard therapy group; in the PILOT trial, 54% of the 61 patients who received liso-cel experienced a complete response. Liso-cel was approved with a Risk Evaluation and Mitigation Strategy because of the risk of fatal or life-threatening cytokine release syndrome and neurologic toxicities.
  • After reviewing 5-year survival results from the DUO trial, the FDA warned of a possible increase in the risk of death with duvelisib (Copiktra; Secura Bio), a PI3K inhibitor, compared with ofatumumab (Arzerra; Genmab/Novartis), an anti-CD20 monoclonal antibody that inhibits B-cell activation. Patients in the trial who received duvelisib also had a higher risk of serious side effects, including infections, diarrhea, lung and intestinal inflammation, skin reactions, and high levels of liver enzymes. Approved in 2018, duvelisib is used to treat adults with chronic lymphocytic leukemia or small lymphocytic lymphoma who have previously received at least two other therapies.
  • Ipsen announced that it will acquire Epizyme, a biopharmaceutical company developing therapies against novel epigenetic targets to treat patients with cancer. Among other assets, Ipsen will gain tazemetostat (Tazverik), a first-in-class EZH2 inhibitor, which is FDA approved to treat certain adults with follicular lymphoma (FL), as well as patients age 16 and older with metastatic or locally advanced inoperable epithelioid sarcoma. The deal is worth approximately $247 million, but milestone payments could increase the value.
  • Kite announced that the European Commission approved axicabtagene ciloleucel (axi-cel; Yescarta) to treat adults with relapsed/refractory FL after at least three systemic therapies. The approval was based on findings from 75 patients in the single-arm, phase II ZUMA-5 trial who met these conditions. The overall response rate to axi-cel, a CD19-directed chimeric antigen receptor T-cell therapy, was 91%; the complete response rate was 77% after 24 months, and the median duration of response was 38.6 months.
  • Study findings published in the Journal of Clinical Oncology indicate that PSA-based endpoints should not be used as surrogates for overall survival (OS) in men whose prostate cancer recurs following surgery (J Clin Oncol 2022 Jun 23 [Epub ahead of print]). Rather, this new analysis of the NRG Oncology/RTOG 9601 trial suggests that metastasis-free survival (MFS) is currently the best surrogate endpoint in this group of patients. MFS has been considered a valid surrogate for OS in men treated for localized prostate cancer.
  • Endpoints News reported that a New York federal judge refused to dismiss a lawsuit against BMS alleging that the company dragged its feet in submitting standard materials to the FDA supporting the approval of liso-cel to skip paying $6.4 billion in contingent value rights. When it bought Celgene in 2019, BMS agreed to make this payment if three particular drugs, including liso-cel, were approved by set dates. The approval came 36 days after the deadline, negating the agreement and prompting UMB Bank to file suit.
  • Nuvation Bio reported that the FDA placed a partial clinical hold on NUV-422, a CDK2/4/6 inhibitor. The company had been enrolling patients in the dose-escalation portion of a phase I monotherapy trial when some of the participants were diagnosed with uveitis, halting further trial enrollment. In light of the partial hold, Nuvation said it will obtain feedback from the FDA and conduct a risk–benefit analysis of its NUV-422 program "to ensure that we deploy our resources on programs that have the highest probability of success and of generating value for patients and our investors."
  • President Joe Biden nominated Arati Prabhakar, PhD, to be director of the Office of Science and Technology Policy. Once confirmed, she will be the president's chief advisor for science and technology, a co-chair of the President's Council of Advisors on Science and Technology, and a member of the president's cabinet. Prabhakar has served as director of the Defense Advanced Research Projects Agency and has led the National Institute of Standards and Technology.

June 17–23

  • JUUL Labs must stop selling and distributing all its electronic cigarette (e-cigarette) devices and pods, which are filled with nicotine-containing liquid that is vaporized and inhaled by users, and products currently on the market must be removed from store shelves, the FDA ordered. The agency said that the company's applications to sell the products "lacked sufficient evidence…that marketing of the products would be appropriate for the protection of the public health." The FDA has said that e-cigarette use has dramatic increased among youth, but the company, which plans to appeal the decision, has advertised its e-cigarettes as a tool to help current smokers quit using traditional combustible cigarettes.
  • Novartis announced that the FDA granted accelerated approval to the combination of dabrafenib (Tafinlar) and trametinib (Mekinist) to treat BRAFV600E-mutant tumors—namely in patients age 6 and older with inoperable or metastatic solid tumors whose disease has progressed following other treatment and who have no satisfactory alternative treatment options. The combination is not indicated for patients with colorectal cancer; dabrafenib is not indicated for patients with wild-type BRAF solid tumors. The decision was based on findings from multiple cohort trials that involved 131 adults and 36 children with 24 types of cancer; the overall response rates (ORR) were 41% and 25%, respectively.
  • Novartis also reported that the European Commission approved capmatinib (Tabrecta) to treat adults with advanced non–small cell lung cancer (NSCLC) harboring alterations leading to MET exon 14 skipping mutations who require systemic therapy following treatment with immunotherapy and/or platinum-based chemotherapy. The approval was based on results of the phase II GEOMETRY mono-1 trial, which demonstrated an ORR of 51.6% in 31 patients who had already received at least two therapies; among 100 patients who had already received at least one systemic therapy, the ORR was 44%. The most common treatment-related adverse events were peripheral edema, nausea, vomiting, and increased blood creatinine.
  • A report from researchers at the American Cancer Society in collaboration with the NCI found more than 18 million Americans who have had cancer were alive in the United States as of January 1, with 12 million (67%) age 65 or older and more than half (53%) diagnosed within the last decade (CA Cancer J Clin 2022 Jun 23 [Epub ahead of print]). They noted that the increased survival was mainly due to a growing and aging population as well as advances in early detection and treatment. However, the researchers said that their data indicate substantial racial disparities in treatment—for example, Black patients are much less likely to have surgery for NSCLC than whites: 49% versus 55%, respectively, for stage I and II disease and 16% versus 22% for stage III.
  • Japanese researchers reported that mRNA vaccines against SARS-CoV-2 are safe and effective in patients being treated for lung cancer with immune checkpoint inhibitors (ICI), such as anti–PD-1, anti–PD-L1, and anti-CTLA4 antibodies (J Thorac Oncol 2022 Jun 22 [Epub ahead of print]). They enrolled 126 patients a in trial to learn whether the incidence of immune-related adverse events (irAE) in these patients was less than 35%, a standard set by earlier studies. They found that 26 patients (20.6%) and seven patients (5.6%) developed new irAEs of any grade pre-and post-vaccination, respectively, but their antibody levels were significantly lower compared with control subjects who did not receive anticancer or ICI therapies.
  • Susan G. Komen for the Cure awarded $21.7 million to fund 48 research projects at 26 academic medical centers in the United States. Of that amount, 79% supports research on the most aggressive breast cancers, metastasis, and recurrence; 33% supports clinical trials; and 20% supports research on eliminating disparities in breast cancer diagnosis and treatment. The organization says it now supports more than 152 active research projects thanks to more than $115 million in funding.

June 10–16

  • The Cancer Grand Challenges program awarded $100 million to four interdisciplinary teams to probe some of the toughest puzzles in cancer; each team will receive $25 million over 5 years. The NCI and Cancer Research UK launched the program to provide funding for researchers around the world "whose novel ideas have the greatest potential to advance cancer research and improve outcomes for people affected by cancer." The teams will be studying the muscle-wasting condition cachexia, the biology of extrachromosomal DNA in cancer, new therapies for solid tumors in children, and what triggers normal cells with cancer-causing mutations to become tumor cells.
  • Researchers reported that treating precancerous anal lesions in people with HIV cut their risk of anal cancer by 57% (N Engl J Med 2022;386:2273–82). Because current screening and treatment recommendations for people with high-grade squamous intraepithelial lesions (HSIL) may vary, researchers launched the phase III ANCHOR trial, assigning 4,459 patients with HIV and HSIL to receive either active monitoring or treatment with ablation, excision, or topical drugs. After a median follow-up of 25.8 months, 21 patients in the active-monitoring group had developed anal cancer compared with nine patients in the treatment group.
  • Roche announced the launch of a human papillomavirus (HPV) self-sampling solution in countries that accept the CE mark, an indicator that a product meets high health, safety, and environmental standards. The solution lets women privately collect a vaginal sample for HPV screening using the Roche cobas HPV test while at a health care facility under the direction of a health care worker. Screening for HPV can identify women at high risk of developing cervical cancer, which is generally caused by HPV, and Roche says that the new test can overcome barriers to testing, such as more invasive collection procedures, previous negative experiences, embarrassment, and cultural influences.
  • In a filing with the U.S. Securities and Exchange Commission, Clovis Oncology voluntarily withdrew its approval for rucaparib (Rubraca) for the treatment of BRCA-mutated ovarian cancer after two or more chemotherapies, effective June 10. The decision was based on overall survival data from the ARIEL4 trial, which were submitted to the FDA. Clovis also requested withdrawal of the treatment indication in Europe.
  • Most oncology therapies are approved more quickly in the United States than in Europe, according to a cross-sectional study (JAMA Netw Open 2022;5:e2216183). Of 89 therapies approved in both the United States and Europe from 2010 to 2019, the FDA approved 85 (95%) before the European Medicines Agency (EMA) did; the median review time was 200 days for the FDA compared with 426 days for the EMA. Thirty-five (39%) of the therapies were approved by the FDA before pivotal studies were published compared with just eight (9%) by the EMA.

June 3–9

This week: Coverage of the 2022 ASCO Annual Meeting and other news

  • In a prospective phase II single-agent trial of the PD-1 inhibitor dostarlimab (Jemperli; GSK) for the treatment of mismatch repair–deficient stage II or III rectal adenocarcinoma, all 12 study participants had a clinical complete response, according to a presentation at the 2022 American Society of Clinical Oncology Annual Meeting in Chicago, IL, and simultaneous publication of the data (N Engl J Med 2022 Jun 5 [Epub ahead of print]). The patients received treatment every 3 weeks for 6 months and were slated to receive standard chemoradiotherapy and surgery afterward—unless they had a clinical complete response. After a median follow-up of 12 months, none of the patients have needed any additional treatment, and none of them have experienced any side effects of grade 3 or higher.
  • For some patients with HER2-negative, hormone receptor–positive metastatic breast cancer who have already received several therapies, taking Gilead's antibody–drug conjugate (ADC) sacituzumab govitecan (Trodelvy) improved progression-free survival by 34% compared with physician's choice of chemotherapy—5.5 months versus 4 months—according to a study presented at the ASCO meeting. The 543 patients participating in the study had an overall response rate of 21% compared with 14% for chemotherapy; the clinical benefit rates were 34% and 22%, respectively. At this first interim analysis, the researchers also reported a nonsignificant trend in overall survival favoring the ADC.
  • Twelve days into his latest stint as the acting director of the NCI, Douglas Lowy, MD, testified before the U.S. House of Representatives Appropriations Committee regarding the NCI's budget for fiscal year 2023. "I just want to assure you that there is really strong bipartisan support for cancer research and the NCI," Lowy told attendees at the ASCO meeting. "Congress has increased the funding for the NCI each of the last 5 years," he said. "With your help and support, it will happen again in 2023."
  • Based on results of a phase II/III trial presented at the ASCO meeting, the combination of two targeted therapies could become a standard treatment for children with BRAF V600–mutant low-grade gliomas. In a 1:1 ratio, 110 children were assigned to receive the inhibitor dabrafenib (Tafinlar; Novartis) plus the MEK inhibitor trametinib (Mekinist; Novartis) or a standard chemotherapy regimen of carboplatin and vincristine. After a median follow-up of 18.9 months, the overall response and clinical benefit rates were 44% versus 11% and 86% versus 46%, respectively; median progression-free survival was 20.1 months versus 7.4 months, respectively.
  • "These are not simple times," said André Ilbawi, MD, cancer control lead at the World Health Organization, during his presentation on international disparities in cancer care and call to action at the ASCO meeting. "Each of us carries an immense professional burden on our shoulders. The world is fractured by conflict, culture wars, identity-based politics. But we as the oncology community have the moral standing and obligation to advance solidarity and social change. If we can come together and deliver on cancer care for all—not as a rallying cry, but as a reality—we will save millions of lives."

In other news:

  • The American Association for Cancer Research released its second Cancer Disparities Progress Report, which noted that the overall cancer mortality rate between Blacks and whites has narrowed from 26% in 2000 to 13% in 2019. However, the report says that many significant disparities remain—for example, Hispanic patients with liver cancer are twice as likely to die from the disease as non-Hispanic whites. To address these gaps, the report calls for several changes, such as greater diversity in clinical trials and the disaggregation of cancer data to account for the heterogeneity of people within racial, ethnic, sexual, and gender minority groups. The report is available at www.CancerDisparitiesProgressReport.org.
  • Foundation Medicine announced that the FoundationOne CDx test was approved by the FDA as a companion diagnostic for use with entrectinib (Rozlytrek; Roche). The test can identify patients with ROS1 fusion–positive non–small cell lung cancer and patients with an NTRK fusion–positive solid tumor who might benefit from entrectinib use. Roche said that this is the first and only approved companion diagnostic that can identify these patients.
  • Federal Trade Commission lawyers posited that sequencing giant Illumina's $8 billion acquisition of Grail would slow efforts to diagnose cancer earlier and limit competition during its closing arguments in an antitrust case, Bloomberg reported. Attorneys for Grail have argued that its platform can detect many cancers for which no screening tests exist and that such tests would be more readily adopted and reach patients more quickly through the merger. After the deal was announced in 2020, lawsuits were filed in the United States and in Europe, where regulators, according to reports, have yet to be convinced of the merger's benefits.

May 2022

May 27–June 2

  • Bristol Myers Squibb (BMS) announced it will acquire Turning Point Therapeutics for $4.1 billion. Turning Point's lead asset is repotrectinib, a next-generation tyrosine kinase inhibitor that targets ROS1 and other NTRK oncogenic drivers of non–small cell lung cancer (NSCLC). BMS expects repotrectinib to receive FDA approval in 2023—and to become a new standard of care for newly diagnosed patients with ROS1-positive NSCLC.
  • It was a busy week at the FDA. Among the goings-on, the agency:
    • Granted accelerated approval to tisagenlecleucel (Kymriah; Novartis), a chimeric antigen receptor T-cell therapy, for the treatment of adults with relapsed/refractory follicular lymphoma after at least two systemic therapies. The decision was based on findings from the ELARA trial, in which 90 patients were treated and followed for a median of 17 months; 86% of them experienced a response, including 68% who had a complete response. Responses were durable, with 85% of complete responders still responding a year later.
    • Approved two nivolumab (Opdivo; Bristol Myers Squibb)-based regimens for newly diagnosed esophageal squamous cell carcinoma deemed inoperable or advanced/metastatic. In the phase III CheckMate 648 trial, all patients who received the PD-1 inhibitor nivolumab plus fluoropyrimidine- and platinum-containing chemotherapy compared with chemotherapy alone demonstrated superior median overall survival (OS)—13.2 months vs. 10.7 months, respectively—and among those with PD-L1–positive tumors—15.4 months vs. 9.1 months, respectively. Nivolumab plus the CTLA4 inhibitor ipilimumab (Yervoy; Bristol Myers Squibb) also improved median OS among all patients compared with chemotherapy—12.8 months vs. 10.7 months, respectively—and in patients with PD-L1–positive tumors—13.7 months vs. 9.1 months, respectively.
    • Greenlighted Amneal Pharmaceuticals' pegfilgrastim-pbbk (Fylnetra), a biosimilar referencing Amgen's Neulasta. The drug is used to treat neutropenia, a common side effect of chemotherapy.
  • Withdrew approval of TG Therapeutics' umbralisib (Ukoniq) for the treatment of marginal zone lymphoma and follicular lymphoma. Updated findings from the UNITY-CLL trial continued to show a possible increased risk of death in patients receiving the PI3Kδ/CK1ε inhibitor.
  • Grail announced that it will work with AstraZeneca (AZ) to develop and commercialize companion diagnostic tests for AZ's therapies. The companies will initially focus on developing liquid biopsies to identify patients with high-risk, early-stage disease and then launch studies across multiple indications over the next several years. In addition, the companies will use Grail's technology to help recruit patients with early-stage disease to participate in AZ's clinical trials.
  • Despite encouraging results in a phase I/II trial, RhoVac reported that its immunotherapeutic onilcamotide (RV001) didn't meet its primary endpoint in the phase IIb BRaVac trial: preventing or delaying disease progression in patients with prostate cancer experiencing a rising PSA level following treatment "with curative intent." The company said it will "undertake a more thorough analysis of the study results, but the primary outcome analysis obviously offers little hope of a license or acquisition deal based on the results of this study alone."

May 20–26

  • The FDA approved azacitidine (Vidaza; Celgene) for children with newly diagnosed juvenile myelomonocytic leukemia. The decision was based on the AZA-JMML-001 trial, in which 18 patients received azacitidine prior to hematopoietic stem cell (HSC) transplantation. Three patients experienced clinical complete remission (CR) and six experienced clinical partial remission, with a median time to response of 1.2 months; 94% underwent HSC transplantation, with a median time to transplantation of 4.6 months.
  • The FDA also approved ivosidenib (Tibsovo; Servier) in combination with azacitidine for patients 75 or older with newly diagnosed acute myeloid leukemia who harbor a susceptible IDH1 mutation or who cannot tolerate intensive induction chemotherapy. The decision was based on the AG120-C-009 trial, in which 146 patients were randomly assigned to receive the combination or placebo plus azacitidine. Thirty-five percent of patients who received ivosidenib had improved event-free survival compared with 16% in the placebo arm; the CR rates were 47% and 15%, respectively, and median overall survival was 24 months and 7.9 months, respectively.
  • The FDA removed the partial clinical hold on the NEON-2 trial evaluating davoceticept (Alpine Immune Sciences), a first-in-class, conditional CD28 costimulator and dual checkpoint inhibitor, in combination with PD1 inhibitor pembrolizumab (Keytruda; Merck) in adult patients with advanced malignancies. During the hold, enrolled patients could continue treatment, but no new participants could join. Following the FDA's review of the company's complete response, which included an assessment of davoceticept's safety and revision of the study protocol, the hold was lifted.
  • SpringWorks Therapeutics announced that a study of nirogacestat met its primary and secondary endpoints in adults with progressing desmoid tumors. In the double-blind, placebo-controlled phase III DeFi trial, the oral gamma secretase inhibitor significantly improved progression-free survival, reducing the risk of disease progression by 71%. As for secondary endpoints, nirogacestat yielded improvements in objective response rate and patient-reported outcomes compared with placebo, and it was generally well tolerated with a manageable safety profile.
  • Pfizer launched a not-for-profit initiative to provide its current and future patent-protected drugs to 45 lower-income countries. The current assortment of 23 medicines and vaccines, which are patented in the United States or the European Union, treat some infectious diseases, rare and inflammatory diseases, and cancers, including certain leukemias, breast cancers, and advanced kidney cancers. Rwanda, Ghana, Malawi, Senegal, and Uganda are the first countries to sign on to the program.
  • Similarly, the Union for International Cancer Control (UICC) and multiple partners established the Access to Oncology Medicines (ATOM) Coalition, which aims to contribute more oncology resources to low- and lower middle–income countries. The coalition will provide drugs and training for their proper use, exchange best practices, and coordinate with international partners. ATOM will build UICC's network of member organizations in selected countries and increase public and private sector partnerships to launch programs that foster access to cancer care.
  • State Attorney General Maura Healey announced that Massachusetts is suing more than a dozen companies that produce and market firefighting foam containing toxic "forever chemicals" that contaminate the water supply and damage the environment. Fire suppressants, known as aqueous film-forming foam, contain perfluoroalkyl and polyfluoroalkyl substances, which have been linked to testicular and kidney cancers and other diseases. 3M, DuPont, and Tyco Fire Products are among the companies named in the lawsuit.

May 13–19

  • Federal agencies, Congress, and others need to improve representation of minority groups and underrepresented populations in clinical trials and research, according to a report from the National Academies of Sciences, Engineering, and Medicine (NASEM 2022 May 17 [Epub ahead of print]). Lack of representation may limit access to medical interventions and new therapies for some patients and increase health disparities, which could cost the United States hundreds of billions of dollars over the next 30 years. Among the report's recommendations: require study sponsors to ensure that trial cohorts reflect the demographics of the condition under study, establish a task force to investigate new incentives for drug and device trials for which enrollment reflects the general population, and press the NIH to consider participant representation when assessing the impact of a grant proposal.
  • The FDA has placed a partial clinical hold on a phase I study of FHD-286 (Foghorn Therapeutics) for patients with relapsed/refractory acute myelogenous leukemia and myelodysplastic syndrome following the death of a patient with potential differentiation syndrome. Patients currently enrolled in the study and benefiting from the BRG1 and BRM inhibitor may continue to receive it, but no new patients can be enrolled until the hold is lifted; the hold does not apply to patients with metastatic uveal melanoma in a separate phase I trial.
  • According to the American Cancer Society, Medicaid expansion under the Affordable Care Act is associated with a 2-year increase in overall survival (OS) in patients newly diagnosed with cancer, especially among non-Hispanic Black people and people living in rural areas (J Natl Cancer Inst 2022 May 18 [Epub ahead of print]). Researchers analyzed data of over 2.5 million patients ages 18–62 in cancer registries from 42 states diagnosed with cancer before and after Medicaid expansion. OS increased from 80.58% to 82.23% in states that expanded Medicaid coverage and from 78.71% to 80.04% in those that didn't—an increase of 0.44% in expansion states after adjusting for sociodemographic factors.
  • Researchers found that children with certain liver tumors have better outcomes when they underwent transplantation rather than having chemotherapy and surgery alone (J Hepatol 2022 May 13 [Epub ahead of print]). Researchers observed that some aggressive tumors have histologic features unlike hepatoblastomas or hepatocellular carcinomas, as well as molecular profiles that don't fit into a single disease category, but both. The team found that these tumors tended to be more resistant to standard chemotherapy and have poor outcomes when not treated with more aggressive surgical approaches, including transplantation, indicating the need for molecular testing to guide treatment.
  • In a case–control study in England and Wales, researchers found that male infertility is associated with a statistically significant increase in men's risk of invasive breast cancer (Breast Cancer Res 2022;24:29). Researchers interviewed 1,998 men diagnosed with the disease between 2005 and 2017 and 1,597 male controls, including questions about infertility and the number of children fathered. They calculated that the infertile men had a significantly higher risk of breast cancer, as did men who had not fathered children, with odds ratios of 2.03 and 1.50, respectively, although the researchers said these results require further investigation.
  • Atara Biotherapeutics announced that Bayer will end their $670 million exclusive worldwide licensing agreement for next-generation mesothelin-directed chimeric antigen receptor T-cell therapies. The collaboration included the development and funding of ATA3271, an armored allogeneic T-cell immunotherapy, and an autologous version, ATA2271, for high mesothelin–expressing tumors, such as malignant pleural mesothelioma and non–small cell lung cancer. The agreement will end in September.
  • Although the company has long used the abbreviation on buildings and company announcements, GlaxoSmithKline officially changed its name to GSK.

May 6–12

  • In the phase I ANTLER trial, Caribou Biosciences' chimeric antigen receptor (CAR) T-cell therapy, CB-010, demonstrated an overall response rate (ORR) of 100% in all five evaluable patients with relapsed/refractory B-cell non-Hodgkin lymphoma; patients had already received a median of three treatments. In addition, 80% experienced a complete response (CR) lasting up to 6 months; three patients developed grade 3 or 4 adverse events within 28 days of treatment. Caribou says that "CB-010 is the first allogeneic anti-CD19 CAR T-cell therapy in the clinic with a PD-1 knockout, a genome-editing strategy designed to limit premature CAR T-cell exhaustion."
  • Nykode Therapeutics reported that its cancer vaccine VB10.16 showed promising efficacy and antitumor activity in patients with advanced human papillomavirus 16–positive advanced cervical cancer when combined with the PD-L1 inhibitor atezolizumab (Tecentriq; Genentech). Interim results from the phase II VB C-02 trial showed a CR in two of 39 patients and a partial response in six more patients after a median follow-up of 6 months; the disease control rate was 64%, and the ORR was 21%. Antitumor activity occurred in both PD-L1–positive and PD-L1–negative patients.
  • Taiho Pharmaceutical will acquire Cullinan Pearl, a subsidiary of Cullinan Oncology, for $275 million upfront and up to $130 million in milestone payments. In addition, Taiho and Cullinan Oncology will collaborate on the development and commercialization of CLN-081/TAS6417, an irreversible EGFR inhibitor that selectively targets cells that express EGFR exon 20 insertion mutations while sparing cells that express wild-type EGFR. Researchers are testing CLN-081/TAS6417 in a phase I/IIa study in patients with non–small cell lung cancer.
  • The Ralph Lauren Corporate Foundation announced it will donate $25 million to five cancer research centers—the single largest commitment made by the foundation in its 20-year history. Participating institutions will be NCI-designated centers: Two of the selected centers are Georgetown Lombardi Comprehensive Cancer Center in Washington, DC, and Memorial Sloan Kettering Cancer Center in New York, NY; three more will be chosen by the foundation and the American Society of Clinical Oncology's Conquer Cancer foundation. The funding will support early cancer detection, prevention, patient navigation, and increased access to clinical trials in underserved communities.

April 29–May 5

  • The FDA granted regular approval to fam-trastuzumab deruxtecan-nxki (Enhertu; Daiichi Sankyo) for patients with inoperable or metastatic HER2-positive breast cancer who have previously received anti-HER2–based regimens. The decision was based on DESTINY-Breast03, the confirmatory trial for this antibody–drug conjugate's accelerated approval in 2019. Among 524 patients who received either fam-trastuzumab deruxtecan-nxki or ado-trastuzumab emtansine (Kadcyla; Genentech), the median progression-free survival was not reached in the fam-trastuzumab deruxtecan-nxki arm versus 6.8 months in the control group. Overall response rates were 82% and 36.1%, respectively.
  • Compared with fulvestrant (Faslodex; AstraZeneca) alone, adding ribociclib (Kisqali; Novartis) increased overall survival (OS) by 16 months in patients with breast cancer. According to an updated analysis of the phase III MONALEESA-3 study, which provided more than 2.5 years of additional follow-up, patients given first-line ribociclib plus fulvestrant upfront were able to delay subsequent chemotherapy by another 1.5 years. To date, ribociclib is the only CDK4/5 inhibitor to show an OS benefit when combined with fulvestrant as first-line therapy for postmenopausal women with advanced or metastatic HR+/HER2- disease.
  • State affirmative action bans significantly reduced the number of minority students enrolled in U.S. public medical schools (Ann Intern Med 2022 May 3 [Epub ahead of print]). The study of 21 affected institutions concluded that underrepresented racial groups—Black, Hispanic, American Indian or Alaska Native, and Native Hawaiian or Pacific Islander—accounted for only 14.8% of medical students 1 year prior to ban implementation; afterward, this percentage dropped by 5.5 points, translating to a relative reduction of 37%. This finding indicates that state-level admissions policies remain an important factor in influencing enrollment diversity.
  • St. Jude Children's Research Hospital will improve diagnostics for pediatric blood cancers globally, providing Oxford Nanopore Technologies' MinION DNA and RNA portable sequencing tool to low- and middle-income countries. A proof-of-concept study has shown that this device could help doctors better distinguish acute myeloid leukemia, B-cell acute lymphoblastic leukemia, and T-cell acute lymphoblastic leukemia (JCO Precis Oncol 2022 Apr 20 [Epub ahead of print]). St. Jude will also make its cloud computing services available to participating hospitals to shorten the turnaround time for these powerful analyses.
  • Gilead paid $300 million to Dragonfly Therapeutics to collaborate on advancing the latter's natural killer (NK) cell engager–based immunotherapies. Gilead now has exclusive worldwide licensing for DF7001, which targets 5T4, a protein associated with poor prognosis in several tumor types, including non–small cell lung cancer, pancreatic cancer, and head and neck squamous cell carcinoma. Gilead also has the option to develop and commercialize additional immune engagers using Dragonfly's Tri-specific NK Engager (TriNKET) platform.
  • The Department of Defense (DOD) will expand its Applied Proteogenomics Organizational Learning and Outcomes (APOLLO) Network. First created in 2016 as part of the original White House Cancer Moonshot initiative, APOLLO successfully created a network of 13 DOD and Veterans Affairs hospitals that launched eight cancer-specific programs, including for lung, breast, prostate, and brain cancers. Now that the Cancer Moonshot program has been revived, APOLLO aims to extend its network to all Defense Health Agency hospitals and widen research efforts to include all cancer types.

April 2022

April 22–28

  • The FDA proposed a ban on menthol flavoring in cigarettes and cigars. This could dramatically lower disease and death resulting from tobacco use, thus playing a crucial role in the Cancer Moonshot program's goal to reduce cancer-related deaths by 50% in the next 25 years. If successful, the ban could diminish the appeal of cigarettes to young people, reduce the likelihood of tobacco experimentation among nonsmokers, and improve smoking cessation rates.
  • Compared with physician's choice of endocrine monotherapy, Roche's oral selective estrogen receptor degrader (SERD) giredestrant failed to improve progression-free survival as a second- or third-line treatment in patients with ER-positive, HER2-negative advanced breast cancer. Overall survival data from this phase II trial, acelERA, are still immature, and investigators noted "encouraging" efficacy, particularly among patients with highly estrogen-dependent disease. Giredestrant is also being evaluated in two phase III trials, lidERA and persevERA, respectively testing the SERD as adjuvant therapy for early disease and combined with the CDK 4/6 inhibitor palbociclib (Ibrance; Pfizer) as initial treatment for metastatic breast cancer.
  • Nkarta reported that two of its lead chimeric antigen receptor (CAR) natural killer (NK) cell therapies, NKX101 and NKX019, showed promising efficacy in acute myeloid leukemia (AML) and non-Hodgkin lymphoma (NHL). NKX101, which targets NKG2D, induced a complete response (CR) rate of 60% with full hematologic recovery among five patients with relapsed/refractory AML. With NKX019, which targets CD19, the CR rate was 50% and the objective response rate was 83% among six patients with NHL. The company said both agents caused fewer adverse side effects compared with CAR T-cell treatments and had no dose-limiting toxicities.
  • Nektar cut 70% of its staff as part of a company reorganization. It will now focus on the development of NKTR-255, an IL15 agonist, to treat both solid and blood cancers, and NKTR-358, in development with Eli Lilly, for the treatment of autoimmune inflammatory diseases. The company will also pursue new research programs, including a collaboration with Biolojic Design utilizing Biolojic's artificial intelligence platform to develop a computationally designed antibody targeting TNFR2.
  • The National Comprehensive Cancer Network (NCCN) updated its COVID-19 vaccination recommendations for patients with cancer (available at https://www.nccn.org/COVID-19). The organization now encourages those who are immunocompromised to receive three primary mRNA COVID-19 vaccines plus two booster shots. The NCCN also provided updated dosing recommendations for pre-exposure prevention with tixagevimab plus cilgavimab (Evusheld; AstraZeneca), information on receiving booster shots following the Johnson & Johnson COVID-19 vaccine, and data on whether receiving vaccines from different companies might affect efficacy.

April 15–21

  • Through the analysis of 851 human cancer cell lines, researchers at the Broad Institute of MIT and Harvard's Cancer Dependency Map project determined that dysregulation of the XPR1-KIDINS220 protein complex leads to toxic buildup of phosphate in ovarian and uterine cancers (Nat Cancer 2022 April 18 [Epub ahead of print]). These cancers frequently overexpress the phosphate importer SLC34A2. By disabling XPR1-KIDINS220, toxic buildup of phosphate leads to cancer cell death, suggesting a novel treatment for these malignancies.
  • An FDA advisory panel voted unanimously that randomized data should be required for approvals of PI3K inhibitors for blood cancers due to concerns about toxicity, overall survival, dose optimization, and limitations of single-arm studies. The Oncologic Drugs Advisory Committee's recommendation aligns with the thinking of federal regulators, which was published last week, that randomized data is imperative for accurate risk–benefit evaluations (Lancet Oncol 2022 Apr 14 [Epub ahead of print]).
  • According to data presented at the American Society of Clinical Oncology's monthly Plenary Series, patients with recurrent/metastatic nasopharyngeal cancer who receive tislelizumab (BeiGene) experience longer progression-free survival (PFS) than those who receive a placebo. In the phase III RATIONALE-309 study, 263 patients received either tislelizumab plus chemotherapy or placebo plus chemotherapy; median PFS was 9.6 months versus 7.4 months, respectively, with a 50% reduction in the risk of disease progression with tislelizumab. Median PFS in the tislelizumab group after a subsequent treatment regimen was not reached, and overall survival (OS) was 23 months; median PFS and OS in the placebo group were 13.9 months and 23 months, respectively.
  • Emory University's Winship Cancer Institute in Atlanta, GA, opened the Rollins Immediate Cancer Center, the state's first center dedicated solely to caring for patients experiencing acute cancer-related symptoms, such as severe pain, high fevers, or vomiting. At the center, oncologists and oncology nurses can appropriately triage patients and diagnose and treat patients with pressing cancer-related needs; patients with life-threatening or complicated medical issues will still visit the emergency room. The center was funded with a $7 million gift from The Ma-Ran Foundation.
  • The Vera Bradley Foundation for Breast Cancer donated $12.5 million to Indiana University (IU) School of Medicine in Indianapolis to fund immunotherapy research on triple-negative breast cancer. Previous support from the foundation has helped the school hire physicians and scientists, upgrade technology, and boost resources to advance targeted breast cancer therapies. To date, the foundation has contributed $37.5 million to the IU School of Medicine for breast cancer research.
  • Noting that 14% of global lung cancer cases are caused by air pollution, The International Association for the Study of Lung Cancer issued a list of steps that should be taken to reduce the risk of the disease. For example, the organization called for, among other things, the restriction of air emission targets "to the lowest levels as recommended by the World Health Organization," disinvestment in fossil fuel companies, and research into the pathophysiological and carcinogenetic effects of a specific type of particulate matter called PM2.5.

April 8–14

This week: Special coverage of the American Association for Cancer Research (AACR) Annual Meeting 2022, as well as other news.

  • Reflecting on changes to clinical trial conduct during the COVID-19 pandemic, Lola Fashoyin-Aje, MD, MPH, of the FDA, said that some traditional requirements, such as having patients return to the study site for in-person consent or to receive medications that could be shipped to their homes, could be waived for cancer clinical trials to optimize trial diversity and participation. There's a general sentiment, she said, that "we cannot and should not reflexively revert to traditional site-centered approaches to our clinical trials. Instead, we should leverage all that we learned during the pandemic to determine best practices," focusing on "patient safety, patient convenience, and trial quality to answer important clinical questions."
  • Lisa Coussens, PhD, formally began her 1-year term as president of the AACR at its annual meeting. A researcher at the Oregon Health and Science University in Portland, she succeeds David Tuveson, MD, PhD, of Cold Spring Harbor Laboratory in New York. (For more information about Coussens, see Cancer Discov 2022 Mar 30 [Epub ahead of print]).
  • In the phase III CheckMate 816 trial, neoadjuvant nivolumab (Opdivo; Bristol Myers Squibb) plus chemotherapy led to significantly longer event-free survival and higher likelihood of a pathologic complete response (pCR) than chemotherapy alone in patients with operable non–small cell lung cancer (NSCLC), researchers reported at the AACR meeting and in The New England Journal of Medicine (N Engl J Med 2022 Apr 11 [Epub ahead of print]). Median event-free survival was 31.6 months in the nivolumab arm compared with 20.8 months in the chemotherapy-alone arm; pCR rates were 24% and 2.2%, respectively. No increase in the incidence of adverse events or impediments to surgery was observed in the nivolumab arm.
  • At the AACR meeting, Grace Dy, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, NY, reported that 2-year overall survival was 32.5% in patients with KRASG12C-mutated NSCLC who received sotorasib (Lumakras; Amgen) in the phase II CodeBreaK 100 study. In addition, the overall response rate was 41%, the disease control rate was 84%, and the median duration of response was 12.3 months—with no new safety concerns. These findings mimic those of previously reported efficacy data for the KRASG12C inhibitor (N Engl J Med 2021;384:2371–81).
  • Dual treatment with KSQ-4279 and a PARP inhibitor showed synergistic activity across different lineages, reported Andrew Wylie, PhD, of KSQ Therapeutics. A potent and selective USP1 inhibitor, KSQ-4279 also showed dose-dependent efficacy and durable tumor regression in ovarian cancer patient-derived xenograft models when combined with olaparib (Lynparza; AstraZeneca). The drug is now being tested in phase I trials in tumors with homologous recombination deficiency.
  • In a phase Ib trial presented at the AACR meeting, the oral ataxia telangiectasia and Rad3-related (ATR) inhibitor elimusertib yielded durable objective responses in patients with a variety of cancers harboring ATM alterations. Some patients experienced grade 3 adverse advents—namely anemia and other hematologic effects that were manageable and reversible. Additional studies assessing elimusertib in combination with PARP inhibitors or PD-1 inhibitors are underway.
  • "One of the key problems in the rare cancer space is lack of appropriate models in which to prosecute hypotheses," said Andrew Futreal, PhD, of The University of Texas MD Anderson Cancer Center in Houston, during his AACR meeting presentation on genomic profiling of patients with rare cancers. As part of the Rare Tumor Initiative, MD Anderson has partnered with the Broad Institute of Harvard and MIT and The Rare Cancer Research Foundation to help develop 2D and 3D models of these diseases to aid in extending research efforts.
  • Speaking at the AACR meeting about prostate ductal adenocarcinoma (PDAC), Christine Iacobuzio-Donahue, MD, PhD, of Memorial Sloan Kettering Cancer Center (MSKCC) in New York, NY, said, "There are evolutionary features of locally advanced PDAC that are clinically relevant." She suggested that future research on this lethal disease should focus on rethinking stromal targeting and investigate the mechanistic underpinnings of phenotypic differences within the disease.
  • Charles Swanton, MD, PhD, of The Francis Crick Institute and University College London in the UK, presented some early results from the TRACERx 421 Patient Cohort comprised of 421 prospectively recruited patients with stage I-IIIA NSCLC. He announced that primary tumor subclone expansion matters and can contribute to worse outcomes and disease recurrence.
  • Broadening the search into autoimmunity gene variants could provide further information regarding antitumor immunity, explained Thomas Gajewski, MD, PhD, of the University of Chicago in Illinois, during his AACR presentation. Inspired by findings that PTPN22 variants predispose individuals to autoimmune diseases, he demonstrated that myeloid cell PTPN22 regulated CD8+ T cell–mediated tumor control.
  • Luis Diaz Jr., MD, of MSKCC spoke about the dichotomy of hypermutagenesis at the AACR meeting. His work revealed that foreignness of a mutation is a driving factor of self-peptidome immune recognition, where those with a greater degree of sequence divergence from the self-peptidome are more responsive to immune checkpoint blockade, ultimately suggesting a strategy for conversion of tumors from immune-cold to more immunogenic.

In other news:

  • GlaxoSmithKline (GSK) will acquire Sierra Oncology, based in San Mateo, CA, for $1.9 billion. GSK will enhance its hematology portfolio—which includes the BCMA-targeted agent belantamab mafodotin (Blenrep) for the treatment of multiple myeloma—with the addition of momelotinib, which is under investigation for the treatment of myelofibrosis. Momelotinib inhibits multiple signaling pathways: ACVR1/ALK2; JAK1, and JAK2; in the phase III MOMENTUM trial, demonstrated statistically significant and clinically meaningful benefits in symptom management, splenic response, and anemia.
  • Four pharmaceutical companies launched the Precision Cancer Consortium (PCC) to boost access to genomic testing for patients with cancer around the world. The PCC aims to increase the use of precision diagnostics such as next-generation sequencing, improve access to routine care and clinical trials, and communicate the value of genomic testing to health care providers. The founding companies are Bayer, GSK, Novartis, and Roche.
  • Toronto, Canada–based Nurosene Health subsidiary NetraMark announced it will collaborate with the Ontario Institute for Cancer Research to identify genetic biomarkers of pancreatic cancer using artificial intelligence (AI). This initiative could increase understanding of how to treat the disease and point to the most effective medication for each patient. Nurosene Health specializes in "delivering innovative AI-based technology solutions that support mental performance and wellness."

April 1–7

  • The FDA approved axicabtagene ciloleucel (axi-cel; Yescarta; Kite/Gilead) as the first CAR T-cell therapy to treat adults with large B-cell lymphoma (LBCL) that is refractory to or relapses within 12 months of receiving first-line chemoimmunotherapy. The decision was based on the landmark ZUMA-7, in which 40.5% of patients who received axi-cel were alive after 2 years compared with 16.3% of those who received standard care. In addition, event-free survival was longer with axi-cel than standard care—8.3 months versus 2 months, respectively.
  • In a study published in the Journal of Clinical Oncology, researchers reported that women with breast cancer have a higher risk of cardiovascular disease than women without the disease (J Clin Oncol 2022 Apr 6 [Epub ahead of print]). In the Pathways Heart Study, researchers compared 13,642 women with breast cancer diagnosed between 2005 and 2013 who were treated with chemotherapy, radiation therapy, or endocrine therapy with 68,202 women without the disease. Although degree of risk varied by treatment, the researchers found that women undergoing breast cancer treatment were more likely to experience stroke, arrhythmia, cardiac arrest, venous thromboembolic disease, cardiovascular disease–related death, and death from any cause compared with women without a history of breast cancer.
  • The UK's National Institute for Health and Care Excellence (NICE) decided to recommend avelumab (Bavencio; Merck/Pfizer) as a first-line maintenance therapy for bladder cancer. NICE initially nixed the PD-L1 inhibitor, saying the benefit didn't justify the cost. However, thanks to a drop in price and additional evidence of a benefit from the company, avelumab will be recommended for use in patients with locally advanced or metastatic urothelial carcinoma whose disease has not progressed after platinum-based chemotherapy.
  • In what the company deems a first of its kind for the pharmaceutical industry, Sanofi launched its Diversity, Equity & Inclusion (DE&I) Board, which includes experts from outside the company. The company said that its strategy is "built around three key pillars: building representative leadership, creating a work environment where employees can bring their whole selves, and engaging with the company's diverse communities." The new DE&I Board will offer advice on how to speed advancements in diversity, equity, and inclusion at the company and monitor progress.
  • American Association for Cancer Research (AACR) members chose Philip Greenberg, MD, as the organization's president-elect for 2022–2023; he will assume the position next week at the AACR 2021 Annual Meeting in New Orleans, LA, when Lisa Coussens, PhD, becomes the AACR president. An internationally recognized pioneer in cancer immunology whose work fueled the advancement of adoptive T-cell therapy, Greenberg heads the immunology program at Fred Hutchinson Cancer Research Center in Seattle, WA. He has served on the AACR's board of directors and the Annual Meeting program committee, among others, and is co–editor-in-chief of the AACR journal Cancer Immunology Research.

March 2022

March 25–31

  • Under President Joe Biden's proposed budget for fiscal year (FY) 2023, the NCI would face a budget cut of $199 million compared with FY2022. If approved by Congress, the NCI would receive $6.714 billion, even though the agency requested $7.766 billion. However, the proposed budget would provide a $41 million increase for cancer programs at the Centers for Disease Control and Prevention and a one-time increase of $20 million for the FDA Oncology Center of Excellence. In addition, the new Advanced Research Projects Agency for Health (ARPA-H) would receive $5 billion.
  • Debate over where ARPA-H will be "housed" has come to an end: It will be part of the NIH, although a few measures have been taken to provide some autonomy to the agency. For example, the director of ARPA-H will report to the secretary of Health and Human Services instead of the NIH director, and it will not be located at the NIH's headquarters in Bethesda, MD.
  • The Telomere to Telomere (T2T) consortium has generated the first gapless sequence of a human genome (Science 2022;376:6588). Analysis of the sequence will offer insight into genomic variations within 622 medically relevant genes and allow researchers to better understand how chromosomes segregate and divide. The work could also lead to more discoveries about how genetic factors contribute to disease. Several related papers were published in the same issue of Science and other journals.
  • Roche/Genentech reported that in the phase III SKYSCRAPER-02 study, the combination of tiragolumab and atezolizumab (Tecentriq) plus chemotherapy failed to improve progression-free survival and overall survival (OS) in patients with extensive-stage small-cell lung cancer. The regimen of the anti-TIGIT and anti–PD-L1 drugs, respectively, continues to be assessed in PD-L1–high patients with non–small cell lung cancer in the phase III SKYSCRAPER-01 trial. Data will be presented at an upcoming medical meeting.
  • Researchers determined that a living-donor liver transplant (LDLT) is a viable treatment alternative to chemotherapy for patients with inoperable colorectal liver metastasis (JAMA Surg 2022 Mar 30 [Epub ahead of print]). Of 10 patients who received an LDLT, the estimated recurrence-free survival after a median of 18 months was 62%; estimated OS was 100%. Recent studies have suggested that patients receiving an LDLT from a living donor live longer than patients with liver cancer who receive a liver from a deceased donor.

March 18–24

  • The FDA approved lutetium Lu 177 vipivotide tetraxetan (Pluvicto; Novartis)—formerly 177Lu-PSMA-617—the first radioligand therapy to treat patients with PSMA-positive metastatic castration-resistant prostate cancer who have already received other therapies. The decision was based on the phase III VISION study, in which patients who received the agent and standard-of-care treatment had a 38% reduction in the risk of death and a 60% reduction in the size of tumors compared with standard care alone.
  • The FDA declined to approve sintilimab (Lilly/Innovent), a PD-1 inhibitor, for the treatment of nonsquamous non–small cell lung cancer. Clinical trials of the drug took place only in China, and regulators expressed concern about the lack of diversity in the trials. In February, a panel of FDA advisers said that the companies should be required to conduct a trial of sintilimab and demonstrate its benefit in a diverse population; the companies are exploring next steps for the drug in the United States.
  • Merck announced that the FDA approved pembrolizumab to treat advanced endometrial carcinoma that is mismatch repair–deficient (dMMR) or microsatellite instability–high (MSI-H) in patients with progressive disease who aren't candidates for surgery or radiation. Among 90 patients enrolled in two cohorts of the KEYNOTE-158 trial, 12% had a complete response and 33% had a partial response. In addition, the agency approved the companion diagnostic VENTANA MMR RxDx Panel (Ventana Medical Systems/Roche Tissue Diagnostics) to select patients with dMMR eligible for treatment; a test from Foundation Medicine to detect MSI-H tumors was already approved.
  • Patients diagnosed with early cervical cancer have a higher likelihood of disease-free survival (DFS) after having a hysterectomy with open surgery compared with minimally invasive surgery (MIS). The DFS for open surgery was 96%, while the MIS DFS was 85%. This final analysis, which was presented at the Society of Gynecologic Oncology Annual Meeting, supports the initial 2018 findings from the Laparoscopic Approach to Cervical Cancer trial, and national guidelines now consider open surgery the standard for early-stage cervical cancer.
  • St. Jude Children's Research Hospital researchers discovered two gene variations associated with accelerated biological aging in survivors of childhood cancer compared with chronologic aging (Genome Med 2022;14:32). Through genome-wide association studies, they tested more than 8 million genetic variants and found two distinct single-nucleotide polymorphisms in the DNA of survivors—one mapped to the SELP gene and the other to the HLA locus—compared with controls. Using this information, they may be able to identify patients at high risk of accelerated aging and find potential drug targets.
  • The annual Monitoring the Future survey, conducted by the University of Michigan, polled teens and found the rate of failed attempts to quit nicotine among adolescents rose to 5.74% in 2020, a level not seen since 2004 (JAMA 2022;327:1179–81). This can largely be attributed to electronic cigarette use. While the survey indicated an overall decline in the use of the devices in 2021, researchers are concerned that electronic cigarette use will increase now that teens have returned to school, which could further increase the percentage of those unable to kick the habit.

March 11–17

  • Merck announced that the FDA approved another indication for olaparib (Lynparza)—this time for the adjuvant treatment of patients with germline BRCA-mutant, HER2-negative high-risk early breast cancer who have already received chemotherapy. The approval was based on findings from the OlympiA trial, in which olaparib reduced the risk of invasive breast cancer recurrences, second cancers, or death by 42% versus placebo. At this week's European Society for Medical Oncology Virtual Plenary, researchers presented updated results showing that the PARP inhibitor reduced the risk of death by 32%, a statistically significant improvement in overall survival (OS).
  • However, Merck said the combination of olaparib and the PD-1 inhibitor pembrolizumab (Keytruda) did not demonstrate an improvement in OS in patients with metastatic castration-resistant prostate cancer compared with the control arm, in which patients received either abiraterone or enzalutamide. As a result, the phase III KEYLYNK-010 trial assessing the combination will be discontinued.
  • Racho Jordanov and Rose Lin, founders of JHL Biotech, were sentenced to a year plus 1 day in prison for stealing trade secrets from Genentech, followed by 3 years of supervised release—including 9 months of home confinement for Jordanov. The two hired former or current Genentech employees to obtain confidential information between 2011 and 2019 to "cheat, cut corners, solve problems, provide examples, avoid further experimentation, eliminate costs, lend scientific assurance, and otherwise help" the start-up, according to the U.S. District Attorney for the Northern District of California. The Taiwanese company used the confidential purloined documents to hasten the development of biosimilars of several drugs, including the anti-CD20 mAb Rituxan (rituximab), the anti-HER2 mAb Herceptin (trastuzumab), and the angiogenesis inhibitor Avastin (bevacizumab).
  • Sanofi's revealed that amcenestrant did not meet its primary endpoint of improving progression-free survival in patients with estrogen receptor (ER)–positive, HER2-negative advanced or metastatic breast cancer whose disease progressed while on or after taking hormone therapies. In the phase II AMEERA-3 trial, the oral selective ER degrader as a monotherapy proved no better than a single-agent endocrine therapy of the physician's choice. Trials evaluating the drug in combination with palbociclib (Ibrance; Pfizer), for example, will continue.
  • In a phase III trial, Exelixis's tyrosine kinase inhibitor (TKI) cabozantinib (Cabometyx) "showed neither improvement nor detriment in OS" when combined with the PD-L1 inhibitor atezolizumab (Tecentriq; Genentech) to treat newly diagnosed advanced hepatocellular carcinoma (HCC) compared with the TKI sorafenib (Nexavar; Bayer), the company announced. As a result, Exelixis will not seek FDA approval for the indication. The drug is already approved to treat multiple malignancies, including advanced renal cell carcinoma and HCC already treated with sorafenib.

March 4–10

  • The U.S. Congress passed a $1.5 trillion spending bill to fund the government for fiscal year (FY) 2022, which had been operating under a series of continuing resolutions since October 1. The NIH received nearly $45 billion, an increase of 4.7% over FY21; the NCI, $6.9 billion, up by 5.3%; the FDA, $3.3 billion, up by 3%; and the Centers for Disease Control and Prevention, $8.5 billion, up by 6.8%—although its cancer programs received an increase of just $4 million. The bill also included $1 billion directed to the U.S. Department of Health and Human Services to launch the Advanced Research Projects Agency for Health to drive transformative biomedical breakthroughs—money that can be used through September 30, 2024.
  • The U.S. Congress also gave the FDA's Center for Tobacco Products the authority to regulate synthetic nicotine. The FDA has had the authority to regulate nicotine derived from tobacco but whether the agency could regulate nicotine from other sources has been unclear. Thus, some companies have continued to sell flavored electronic cigarettes, which appeal to children and teenagers, that contain synthetic nicotine. The agency can now regulate nicotine no matter its source; companies need to submit new product applications for any items containing synthetic nicotine—unless they had already been pulled from the market—within 90 days.
  • Regulatory Focus reported that a newly introduced bill would codify the FDA's authority requiring drug companies to complete postmarking studies on agents granted accelerated approval. Introduced by Rep. Frank Pallone (D-NJ), the Accelerated Approval Integrity Act would limit the amount of time drugs could stay on the market without confirming their clinical benefit to 5 years. Under the current system, Pallone said, drugs have been allowed to stay on the market "for far too long without clinical trials" demonstrating their value.
  • Postmenopausal patients with HR-positive, HER2-negative metastatic breast cancer had a significant overall survival (OS) benefit with ribociclib (Kisqali; Novartis) plus endocrine therapy, researchers reported (N Engl J Med 2022;386:942–50). With the CDK4/6 inhibitor and the aromatase inhibitor letrozole, patients experienced a median overall survival OS of 63.9 months compared with 51.4 months with hormone therapy alone. This is the first study to show a survival advantage with a CDK4/6 inhibitor plus an aromatase inhibitor as a first-line treatment in these patients, prompting researchers to say that it should become standard of care for most.
  • Adding bortezomib to chemotherapy significantly improves overall survival in children and young adults just diagnosed with T-cell lymphoblastic lymphoma (T-LL) or acute lymphocytic leukemia (ALL), researchers reported (J Clin Oncol 2022 Mar 10 [Epub ahead of print]). The 4-year event-free survival for patients with T-LL who received chemotherapy alone was 76.5% compared with 86.4% for those who received the proteasome inhibitor as well; the 4-year OS was 78.3% and 89.5%, respectively. There was no significant improvement with bortezomib in patients with ALL.

February 25–March 3

  • During his State of the Union address, President Joe Biden emphasized his goal to cut cancer death rates by at least 50% over the next 25 years by reigniting the Cancer Moonshot program launched in 2016 under President Barack Obama. The Moonshot will largely focus on screening, prevention, and early detection initiatives. He then called upon Congress to fund the Advanced Research Projects Agency for Health (ARPA-H) to drive breakthroughs in cancer and other conditions; a bill passed last year by the U.S. House of Representatives would provide $3 billion to establish ARPA-H.
  • After years of legal wrangling, the U.S. Patent and Trademark Office ruled that the genome editing technology CRISPR belongs to the Broad Institute of Harvard and Massachusetts Institute of Technology (MIT). In 2012, Jennifer Doudna, PhD, of the University of California, Berkeley, and Emmanuelle Charpentier, PhD, of the Max Planck Institute for Infection Biology in Berlin, Germany, showed how CRISPR could be used to edit DNA in test tubes; less than 6 months later, Feng Zhang, PhD, of Cambridge, MA's MIT, and colleagues demonstrated that CRISPR could be used to edit DNA in eukaryotic cells (Science 2012;337:816–21; Science 2013;339:819–23). The patent ruling hinged on Zhang's group being the first to apply the technology to mouse and human cells.
  • Legend Biotech and Janssen announced that the FDA approved ciltacabtagene autoleucel (cilta-cel; Carvykti) to treat adults with relapsed or refractory multiple myeloma who have already received at least four therapies. A chimeric antigen receptor T-cell therapy, cilta-cel was approved based on the pivotal CARTITUDE-1 study, which demonstrated an overall response rate of 98% and a stringent complete response rate of 78%. Cilta-cel is the second CAR T-cell therapy approved for multiple myeloma, following idecabtagene vicleucel (Abecma; Bristol Meyers Squibb/2seventy bio).
  • Writing on Medium, six leaders in the life sciences industry called for businesses to pledge to "cease all business involvement in Russia" in response to that nation's unprovoked attack on Ukraine. Leaders of dozens of companies involved in funding and conducting cancer research—including Mirati, Seagen, Astellas Biopharma, Ikena Oncology, and Arch Oncology—subsequently signed the pledge. As of March 3, more than 700 people had cosigned the letter.
  • CTI Biopharma announced that the FDA granted accelerated approval to pacritinib (Vonjo) for the treatment of myelofibrosis. Pacritinib is a novel oral kinase inhibitor with specificity for JAK2 and IRAK1, without inhibiting JAK1. Approval was based on the phase III PERSIST-2 study, in which 29% of patients with baseline platelet counts below 50 x 109/L treated with 200 mg of pacritinib had a reduction in spleen volume of at least 35%, compared with 3% of patients receiving best available therapy.
  • Cambridge, MA–based Epizyme said it will cut 12% of its staff and end two clinical trials involving its EZH2 inhibitor tazemetostat (Tazverik): the phase II SYMPHONY-2 trial testing a combination of tazemetostat and rituximab in patients with follicular lymphoma (FL), and the phase I EZH-1301 basket trial assessing tazemetostat in combination with a variety of other drugs to treat solid tumors. Tazemetostat is FDA-approved to treat FL and epithelioid sarcoma.

February 2022

February 18–24

  • Researchers reported that, for patients with previously untreated chronic lymphocytic leukemia (CLL), taking ibrutinib (Imbruvica; AbbVie/Janssen) plus venetoclax (Venclexta; AbbVie/Genentech) for a fixed duration could result in deep, durable responses and provide meaningful clinical benefit, even in those with high-risk disease (Blood 2022 Feb 23 [Epub ahead of print]). In the phase II CAPTIVATE study, 159 patients received three cycles of ibrutinib followed by 12 cycles of the combination, with both drugs taken orally. For the 136 patients without del(17p), the complete response (CR) rate was 56%; for the entire group, the CR rate was 55%, and the 24-month progression-free survival (PFS) and overall survival (OS) rates were 95% and 98%, respectively.
  • Atara Biotherapeutics reported that enrollment in a clinical study of ATA2271 has been voluntarily paused due to the death of a patient with advanced, recurrent malignant pleural mesothelioma who had a history of multiple cancers and other comorbidities. Researchers are gathering information to determine the precise relationship between the death and the treatment. ATA2271 is a next-generation autologous chimeric antigen receptor T-cell therapy that targets mesothelin.
  • Merck/EMD Sorono's tepotinib (Tepmetko) was approved by the European Commission to treat adults who have advanced non–small cell lung cancer (NSCLC) with MET exon 14 skipping alterations and require systemic therapy following treatment with immunotherapy and/or platinum-based chemotherapy. The approval was based on results of the pivotal phase II VISION study (N Engl J Med 2020;383:931–43). Researchers are now assessing the combination of tepotinib and osimertinib (Tagrisso; AstraZeneca) in patients with MET-amplified advanced or metastatic NSCLC and activating EGFR mutations that progressed after first-line treatment with osimertinib.
  • Seagen and Genmab announced that tisotumab vedotin (Tivdak) demonstrated a manageable safety profile and promising preliminary antitumor activity in patients with squamous cell carcinoma of the head and neck, with an objective response rate of 16% (five of 31 patients). In the phase II innovaTV 207 trial, the median follow-up was 10 months, the disease control rate was 58.1%, median PFS was 4.2 months, and median OS was 9.4 months. An antibody–drug conjugate, tisotumab vedotin received accelerated approval from the FDA in September 2021 for previously treated recurrent or metastatic cervical cancer.
  • The FDA authorized marketing of the first condoms specifically indicated for use during anal sex to reduce the spread of sexually transmitted infections (STI), such as human immunodeficiency virus and human papillomavirus (HPV). The condoms, marketed as One Male Condom (Global Protection Corp.), can also be used during vaginal intercourse to reduce the risk of pregnancy and transmission of STIs. HPV is the most common STI and is a common cause of cervical, anal, penile, and oropharyngeal cancers.

February 11–17

  • Robert Califf, MD, was confirmed as FDA Commissioner by the U.S. Senate by a vote of 50–46. He replaces Janet Woodcock, MD, who held the role on an interim basis since Stephen Hahn, MD, who was appointed by President Donald Trump, left the FDA on January 20, 2021.
  • President Joe Biden tapped two scientists to handle the responsibilities of Eric Lander, PhD, who resigned earlier this month as director of the White House Office of Science and Technology Policy (OSTP) and as Science Advisor to the President, on an interim basis. Alondra Nelson, PhD, currently OSTP's deputy director for Science and Society, will perform the duties of the OSTP director; Francis Collins, MD, PhD, who recently stepped down as NIH director, will serve as science advisor and as co-chair of the President's Council of Advisors on Science and Technology "until permanent leadership is nominated and confirmed," the White House said.
  • A study conducted at Moores Cancer Center at University of California San Diego Health found that significant increases in the severity of breast cancer diagnoses exist due to the COVID-19 pandemic. In 2019, 63.9% of breast cancers diagnosed there were classified as stage I compared with 51.3% in 2020; stage IV disease was diagnosed in 1.9% and 6.2%, respectively (JAMA Netw Open 2022;5:e2148581). Data from January through March 2021 showed a continuing trend, with 41.9% of patients diagnosed with stage I disease compared with 8% for stage IV disease.
  • At the American Society of Clinical Oncology (ASCO) Genitourinary (GU) Cancers Symposium in San Francisco, CA, researchers reported that Bayer's darolutamide (Nubeqa) plus androgen deprivation therapy (ADT) and docetaxel significantly increased overall survival in patients with metastatic hormone-sensitive prostate cancer compared with ADT plus docetaxel (N Engl J Med 2022 Feb 17 [Epub ahead of print]). In the phase III ARASENS trial, the drug trio reduced the risk of death by 32.5% compared with ADT plus docetaxel. After 4 years, survival was higher with darolutamide than with placebo—62.7% versus 50.4%—with no major differences in adverse events. Darolutamide is approved for the treatment of patients with nonmetastatic castration-resistant disease.
  • Also at the ASCO GU Symposium, researchers announced that AstraZeneca's PARP inhibitor olaparib (Lynparza) plus abiraterone yielded statistically significant and clinically meaningful improvement in radiographic progression-free survival (rPFS) as a first-line treatment for metastatic castration-resistant prostate cancer compared with standard-of-care abiraterone regardless of homologous recombination repair gene mutations. In an interim analysis, the addition of olaparib reduced the risk of disease progression or death by 34%. Median rPFS was 24.8 months for olaparib plus abiraterone versus 16.6 months for abiraterone alone.

February 4–10

  • Presidential Science Advisor and Director of the Office of Science and Technology Policy (OSTP) Eric Lander, PhD, resigned from his Cabinet-level position on February 7, after a Politico article reported that he created a toxic workplace and bullied and mistreated staff. His departure raises questions about the future of the Advanced Research Projects Agency for Health—intended to accelerate biomedical research for widespread diseases—and the reboot of the Cancer Moonshot announced by President Joe Biden last week. The White House has not yet announced an acting director for the OSTP.
  • In a nearly unanimous vote of 14–1, the FDA's Oncologic Drugs Advisory Committee recommended against approving the PD-1 inhibitor sintilimab (Eli Lily/Innovent) to treat non–small cell lung cancer based on the findings of the ORIENT-11 study. FDA officials who attended the meeting criticized the companies for submitting an application for approval based solely on data from China, which doesn't reflect the heterogenous population in the United States. In addition, the FDA representatives criticized the companies for failing to alert patients that the standard of care had changed to the PD-1 inhibitor pembrolizumab (Keytruda; Merck) and to offer patients the opportunity to take that drug instead.
  • Researchers reported that patients with cervical cancer who received the PD-1 inhibitor cemiplimab survived significantly longer than those who received investigator's choice of single agent chemotherapy for recurrent disease following initial treatment with platinum-based chemotherapy (N Engl J Med 2022;386:544–55). For the 304 women who received the Regeneron/Sanofi drug in the phase III trial, the median overall survival was 12 months compared with 8.5 months in the 304 women who received chemotherapy. Notably, objective responses occurred in patients with PD-L1 expression greater than 1% and less than 1%—18% and 11% respectively.
  • In patients with early triple-negative breast cancer, neoadjuvant pembrolizumab plus chemotherapy, followed by adjuvant pembrolizumab after surgery, resulted in significantly longer event-free survival than neoadjuvant chemotherapy alone (N Engl J Med 2022;386:556-67). After a median follow-up of 39.1 months, the estimated event-free survival at 36 months was 84.5% compared with 76.8%, respectively. Researchers reported that adverse events occurred mainly during neoadjuvant treatment and were consistent with what has been previously reported.
  • The FDA issued its first Notice of Noncompliance to Acceleron Pharma for failure to submit required summary results of a trial to ClinicalTrials.gov; the agency had previously sent Acceleron a Pre-Notice of Noncompliance to the company to encourage the company to post findings. The clinical trial in question evaluated the safety and effectiveness of Acceleron's ALK1 inhibitor dalantercept in combination with the tyrosine kinase inhibitor axitinib (Inlyta; Pfizer) to treat patients with advanced renal cell carcinoma. The company has 30 days to submit the required information or face civil monetary penalties.
  • The prospective phase II GALAHAD trial found that about one third of patients with previously treated BRCA-mutant metastatic castration-resistant prostate cancer responded to niraparib (Nerlynx; Puma Biotechnology), a PARP inhibitor (Lancet 2022 Feb 4 [Epub ahead of print]). After a median follow-up of 10 months, the objective response rate in the cohort of 76 patients with measurable disease was 34.2%. The most common treatment-emergent adverse events of any grade were nausea, anemia, and vomiting (58%, 54%, and 38%, respectively); the most common grade 3 or higher side effects were anemia, thrombocytopenia, and neutropenia (33%, 16%, and 10%, respectively).

January 28–February 3

  • The FDA is investigating a possible increased risk of death with umbralisib (Ukoniq; TG Therapeutics), which is approved to treat adults with certain marginal zone and follicular lymphomas, while it continues to evaluate findings of the phase IIb/III UNITY trial testing the drug. The agency has also suspended enrollment of new patients in other clinical trials of umbralisib, the only oral inhibitor of PI3Kδ and CK1ε. Last month, TG Therapeutics announced a partial clinical hold on trials testing the combination of umbralisib and ublituximab, an investigational glycoengineered mAb targeting CD20-expressing B cells.
  • Regeneron Pharmaceuticals and Sanofi announced the withdrawal of their application for cemiplimab (Libtayo) as a second-line treatment for advanced cervical cancer after the companies and the FDA couldn't agree on some postmarketing studies; discussions with regulators outside the United States are continuing. A PD-1 inhibitor, cemiplimab is approved in certain patients with advanced basal cell carcinoma, cutaneous squamous cell carcinoma, and non–small cell lung cancer (NSCLC).
  • In a phase II/III study, the MEK inhibitor trametinib (Mekinist; Novartis) reduced the risk of disease progression or death in patients with low-grade serous ovarian carcinoma by 52% compared with standard-of-care therapies, with an objective response rate of 26%, researchers reported (Lancet 2022;399:541–53). Median progression-free survival with trametinib was 13 months compared with 7.2 months for standard treatment, and the median overall survival (OS) was 37.6 months compared with 29.2 months, respectively. The drug is approved by the FDA for use with dabrafenib (Tafinlar; Novartis) for certain patients with BRAFV600-positive malignancies, including melanoma, NSCLC, and anaplastic thyroid cancer.
  • According to long-term results of the PREOPANC trial, neoadjuvant chemoradiotherapy significantly improved OS in patients with pancreatic cancer compared with standard adjuvant gemcitabine-based chemoradiotherapy, researchers reported. Earlier trial results failed to demonstrate improved OS after a median of 27 months (J Clin Oncol 2020;38:1763–73). Now, after a median of 59 months, neoadjuvant therapy with gemcitabine-based treatment has proven superior: Despite a small difference in median OS between the groups—15.7 months versus 14.3 months, respectively—the estimated 3-year OS was 27.7% compared with 16.5%, respectively, and the 5-year OS was 20.5% compared with 6.5%.
  • The International Atomic Energy Agency (IAEA) announced the launch of an initiative to fight cancer by helping to provide care in low- and middle-income countries in Africa and other parts of the world. The agency will work closely with donors and countries receiving funding to establish facilities for radiotherapy, medical imaging, and nuclear medicine to detect and treat cancers. The IAEA noted that of the African Union's 55 members, more than 20 nations do not have a single radiotherapy machine.

January 2022

January 21–27

  • The FDA greenlighted Immunocore's tebentafusp-tebn (Kimmtrak) for the treatment of HLA-A*02:01–positive adults with inoperable or metastatic uveal melanoma. The decision was based on the results of the phase III IMCgp100-202 clinical trial, in which overall survival was 73% in the tebentafusp group compared with 59% in the control group after 1 year (N Engl J Med 2021;385:1196–206). Tebentafusp-tebn is the first bispecific T-cell engager approved by the agency to treat a solid tumor and the only FDA-approved therapy for this indication.
  • The FDA placed a partial clinical hold on Gilead's studies testing magrolimab plus azacitidine due to what the company called "an apparent imbalance in investigator-reported suspected unexpected serious adverse reactions between study arms." Magrolimab is a potential first-in-class investigational mAb against CD47 and a macrophage checkpoint inhibitor designed to interfere with recognition of CD47 by the SIRPα receptor on macrophages, blocking the "don't eat me" signal used by cancer cells to avoid ingestion by macrophages. It is under evaluation for the treatment of hematologic malignances, such as myelodysplastic syndrome, and solid tumors.
  • Speaking at the B. Riley Securities' 2022 Virtual Oncology Investor Conference, TG Therapeutics' CEO announced that the FDA placed a partial hold on studies of its "U2" combination—umbralisib (Ukoniq) and ublituximab—for chromic lymphocytic leukemia and non-Hodgkin lymphoma. The hold wasn't prompted by new data, but over "earlier concerns" expected to be addressed at a spring meeting of the FDA's Oncologic Drugs Advisory Committee. Umbralisib, approved to treat adults with relapsed/refractory marginal zone lymphoma (MZL) or relapased/refractory follicular lymphoma (FL), is the only oral inhibitor of PI3Kδ and CK1ε; ublituximab is an investigational glycoengineered mAb targeting CD20-expressing B cells.
  • Incyte announced that it will no longer seek FDA approval for its PI3Kδ inhibitor, parsaclisib, for the treatment of relapsed/refractory FL, MZL, and mantle cell lymphoma, saying that confirmatory studies in support of the drug's accelerated approval could not be "completed within a time period that would support the investment." The decision relates only to those indications in the United States. The company will also opt out of continuing the development of MCLA-145, a bispecific antibody under study for the treatment of solid tumors, with Merus.
  • According to findings from a just-published study, deaths from ovarian cancer are predicted to drop by 17% in the UK and by 7% in European Union (EU) nations in 2022 compared with 2017, although the effect of COVID-19 remains unclear (Ann Oncol 2022 Jan 25 [Epub ahead of print]).The researchers attributed the anticipated declines largely to long-term use of oral contraceptives. The report also estimates that overall cancer mortality rates in the EU will drop by 6% in men and 4% in women between 2017 and 2022.
  • In a prospective study of 32 patients with HIV and cancer, Merck's PD-1 inhibitor pembrolizumab (Keytruda) reversed human immunodeficiency virus (HIV) latency in CD4+ T cells, which express PD-1 and are preferentially infected with HIV (Sci Transl Med 2022;14:eabl3836). Latency reversal is a method of inducing HIV antigen expression, which could prompt the proliferation of HIV-targeting CD8+ T cells. "Together with enhanced immune clearance, this approach could potentially eliminate cells that contain replication-competent HIV," the researchers wrote.

January 14–20

  • IBM announced the sale of its Watson Health division to Francisco Partners, a global firm that invests in technology companies, including those focused on health care. Launched in 2015, Watson Health spent billions of dollars to collect health information and patient data to create artificial intelligence tools to aid in drug discovery, offer advice on cancer care, and drive other efforts. However, Watson Health failed to live up to expectations and lost substantial sums, prompting the sale of its assets; financial details weren't disclosed.
  • Gilead announced that it will withdraw two indications for idelalisib (Zydelig): relapsed follicular B-cell non-Hodgkin lymphoma and relapsed small lymphocytic leukemia. In 2014, the FDA granted accelerated approval to idelalisib to treat these conditions, contingent upon receiving additional evidence of clinical benefit. However, the company said that patient enrollment in a confirmatory study proved challenging, prompting the withdrawal of these indications in the United States.
  • According to data presented at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, patients with advanced biliary tract cancer who received the PD-L1 inhibitor durvalumab (Imfinzi; AstraZeneca) and chemotherapy as their first treatment lived longer than those who received chemotherapy alone. In the phase III TOPAZ-1 trial, patients who received the combination experienced a 25% reduction in the risk of disease progression or death compared with standard-of-care chemotherapy. Median progression-free survival was 7.2 months and 5.7 months, respectively, potentially making durvalumab plus chemotherapy a new standard of care.
  • Results from the phase III HIMALAYA trial, also presented at the ASCO Gastrointestinal Cancers Symposium, demonstrated that durvalumab plus the CTLA4 inhibitor tremelimumab (AstraZeneca) significantly improved overall survival in patients with advanced, inoperable hepatocellular carcinoma compared with patients who received durvalumab alone or monotherapy with the multikinase inhibitor sorafenib (Nexavar; Bayer). After 3 years, 30.7% of those who received the combination were still alive compared with 24.7% who received durvalumab and 20.2% who received sorafenib. The overall response rates were 20.1%, 17%, and 5.1%, respectively.
  • Scotland approved AstraZeneca's osimertinib (Tagrisso) as a first-line therapy for adults with locally advanced or metastatic non–small cell lung cancer with activating EGFR mutations. The approval was based on the phase III FLAURA trial, which randomly assigned 556 patients to receive osimertinib or one of two other EGFR tyrosine kinase inhibitors. Patients who received osimertinib lived a median of 38.6 months compared with 31.8 months for patients in the comparison group; those who received osimertinib also reported fewer adverse events.

January 7–13

  • In a deal worth up to $5.2 billion, Sanofi announced it will collaborate with Exscientia to develop up to 15 novel small-molecule candidates to treat cancer and immune-mediated diseases, taking advantage of Exscientia's artificial intelligence (AI) expertise. By applying AI and machine learning to tissue samples, researchers will shorten drug discovery and development times—and design higher-quality and more-effective targeted therapies, the companies said. Exscientia will initially receive $100 million, with additional payments for meeting specific milestones.
  • Daiichi Sankyo announced that it will shutter Plexxikon at the end of March. The Japanese company said that it wanted to maximize its investments in three antibody–drug conjugates for cancer, including, in partnership with AstraZeneca, trastuzumab deruxtecan (Enhertu); trastuzumab deruxtecan is approved to treat HER2-positive breast cancer and gastric cancers. Plexxikon's portfolio includes the BRAF inhibitor vemurafenib (Zelboraf) and the CSF1R inhibitor pexidartinib (Turalio).
  • Takeda announced it will acquire Adaptate Biotherapeutics to obtain Adaptate's antibody-based γδ T-cell engager platform, including preclinical and discovery pipeline programs. The γδ T-cell engagers are designed to modulate γδ T-cell–mediated immune responses at tumor sites while sparing healthy cells. Financial terms were not disclosed.
  • Three European organizations launched an initiative to "transform how clinical trials are initiated, designed, and run," dubbed Accelerating Clinical Trials in the EU (European Union; available at https://www.ema.europa.eu/en). The aim, according to the European Commission (EC), the Heads of Medicines Agencies, and the European Medicines Agency, is to "further develop the EU as a focal point for clinical research, further promote the development of high-quality, safe, and effective medicines, and to better integrate clinical research in the European health system." Among the measures: greater use of innovative clinical trial designs; an increased number of large, international trials, especially at academic medical centers; and harmonized regulatory requirements among EU nations.
  • The FDA gave Allogene the OK to resume testing its allogeneic chimeric antigen receptor (CAR) T-cell therapies. The agency had placed a clinical hold on five of the company's trials of "off-the-shelf" CAR therapies in October after a chromosomal abnormality was detected in a patient with blood cancer who received ALLO-501a. An investigation determined that the anomaly wasn't related to the company's gene editing and manufacturing processes and had no clinical significance.
  • The EC approved Amgen's sotorasib (Lumakras) for patients with KRASG12C-mutated advanced non–small cell lung cancer (NSCLC). The decision was based positive results from the phase II CodeBreaK 100 clinical trial in which 126 patients with NSCLC and the mutation demonstrated an objective response rate of 37.1% and a median duration of response of 11.1 months. Sotorasib is now approved in nearly three dozen countries.

December 30–January 6

  • New recommendations for COVID-19 vaccination for people with cancer were issued by the National Comprehensive Cancer Network (available at https://www.nccn.org/COVID-19). Among the recommendations: Patients with cancer should get fully immunized—including third doses and/or any approved boosters, preferably with mRNA vaccines—and patients receiving hematopoietic cell transplantation or chimeric antigen receptor T cells should wait 3 months after treatment to receive a vaccine to maximize its efficacy. The guidance also offers information on the preventive use of tixagevimab–cilgavimab (Evusheld; AstraZeneca), a long-acting combination of monoclonal antibodies directed against the SARS-CoV-2 spike protein.
  • Researchers showed that 48% of 90 women with advanced endometrial cancer experienced a complete or partial response (PR) to the PD-1 inhibitor pembrolizumab (Keytruda; Merck); all had microsatellite instability–high or mismatch repair–deficient tumors and had previously been treated for the disease (J Clin Oncol 2022 Jan 6 [Epub ahead of print]). Median duration of response and median overall survival were not reached; median time from first dose to data cutoff was 42.6 months. About three quarters of the patients had at least one treatment-related adverse event (TRAE), with 12% experiencing grade 3 or 4 TRAEs.
  • In Massachusetts, a statewide ban on menthol-flavored tobacco products led to a significant drop in cigarette sales, researchers reported (JAMA Intern Med 2022 Jan 4 [Epub ahead of print]). After the ban was implemented in June 2020, the unadjusted 4-week sales of packs of cigarettes per 1,000 people dropped for menthol (404.93 to 32.24), nonflavored (916.37 to 856.79), and all (1,321.32 to 887.69) cigarettes. Compared with states without local or statewide bans, the adjusted 4-week sales of all cigarettes decreased by 282.65 packs per 1,000 people in Massachusetts.
  • Eleven of 33 evaluable women with advanced ovarian cancer had a PR to STRO-002, a folate receptor alpha (Fol-Rα)–targeting antibody–drug conjugate, Sutro Biopharma announced. Also in the ongoing phase I trial, eight of 17 patients who started at the higher of two drug doses experienced a PR. Higher Fol-Rα expression levels correlated with higher response rates.
  • Curis announced updated clinical data from its phase I/II open-label study of CA-4948, a small-molecule IRAK4 inhibitor, in patients with relapsed or refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS) and a U2AF1 or SF3B1 spliceosome mutation. Among five evaluable patients with AML, the rate of complete remission and complete remission with partial hematologic recovery was 40%; among seven patients with MDS, the objective response rate was 57%. IRAK4 plays an essential role in the Toll-like receptor and IL1 receptor signaling pathways.
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