• BREAKING: President Joe Biden announced that W. Kimryn Rathmell, MD, PhD, MMHC, will be the new director of the NCI. Rathmell is currently physician-in-chief and chair of the Department of Medicine at Vanderbilt University Medical Center in Nashville, TN. An internationally recognized expert in kidney cancer, her research focuses on the underlying drivers of the disease through genetic, molecular, and cell biology to improve how patients fare. She has also had a leadership role with the NIH Cancer Genome Atlas and the NCI’s Board of Scientific Advisors, as well as the U.S. Department of Defense Kidney Cancer Research Program.
• The FDA approved the tyrosine kinase inhibitor (TKI) repotrectinib (Augtyro; Bristol Myers Squibb) to treat patients with advanced or metastatic non–small cell lung cancer harboring a ROS1 fusion. The decision was based on the results of the TRIDENT-1 trial, among 71 patients who were TKI-naïve, the overall response rate (ORR) was 79%, with 6% achieving a complete response (CR), and the median duration of response (DOR) was 34.1 months. Among 56 patients who had already tried a ROS1 TKI but no chemotherapy, the ORR was 38%, with 5% achieving a CR, and the median DOR was 14.8 months.
• Bayer will withdraw copanlisib (Aliqopa) from the market. In 2017, based on the results of the phase II CHRONOS-1 study, the FDA granted accelerated approval to the kinase inhibitor to treat follicular lymphoma with PI3Kα and PI3Kδ isoforms expressed in malignant B cells. However, in the confirmatory CHRONOS-4 study, adding copanlisib to standard immunochemotherapy regimens did not show a benefit in progression-free survival compared with immunochemotherapy alone.
• Spearheaded by the Cancer Moonshot in collaboration with the Centers for Medicare & Medicaid Services and the American Medical Association, the Biden Administration announced that Medicare will pay for patient navigators beginning January 1, a service immediately reimbursable through private health insurers. The crucial support navigators can provide hasn’t been readily "available to many Americans because the proper billing codes didn’t exist," said First Lady Jill Biden, but "now that we’ve put these codes in place, we need medical practices and insurance companies to do all they can to get this care to patients and their families… so no one has to face cancer alone."

• During the annual meeting of the Friends of Cancer Research, newly installed NIH Director Monica Bertagnolli, MD, said that enrollment in government-funded clinical trial is behind trials supported by the pharmaceutical industry, which she called a "failure," STAT reported. "If you just look at the number of patients who go on government-funded trials, it’s been completely flat over the last decade," while there’s been a commitment to increasing enrollment in company trials, she said. Although great progress has been made through those trials, she argued that the NIH can play a role in addressing questions that are "not of central interest to pharma."
• Principal Deputy FDA Commissioner Janet Woodcock, MD, will retire in early 2024, multiple media outlets reported. She joined the agency’s biologics center in 1986 and became director of its drug center in 1994, where she made significant changes to drug regulation, such as creating a more predictable route for drug reviews and approvals. She also helped expand the program to approve generic medicines and advised several FDA commissioners during her long tenure. But she will also be remembered for some questionable decisions, such as approving Biogen’s Aduhelm over the recommendation of an advisory committee.

• Monica Bertagnolli, MD, took the helm of the NIH, replacing Lawrence Tabak, DDS, PhD, who had been serving as the agency’s acting director for nearly 2 years. She had been serving as director of the NCI, a position she held since October 2022 when President Joe Biden nominated her for the role; she was confirmed by the U.S. Senate in a 62–36 bipartisan vote on November 7. NCI Principal Deputy Director Douglas Lowy, MD, will serve as the NCI’s acting director until Biden appoints a new director.
• Takeda announced that the FDA approved fruquintinib (Fruzaqla)—the only selective inhibitor of VEGF-1, -2, and -3—for adults with previously treated metastatic colorectal cancer regardless of biomarker status. The approval was based on data from two phase III trials: the international FRESCO-2 trial and the FRESCO trial, which was conducted in China (Lancet 2023;402:41–53; JAMA 2018;319:2486–96); both showed significant improvements in overall survival and progression-free survival. The most common adverse reactions to fruquitinib included hypertension, hand-foot skin reactions, proteinuria, and hoarseness.
• BioNTech inked a deal potentially worth more than $1 billion with China’s Biotheus to develop, manufacture, and commercialize PM8002—a bispecific antibody targeting PD-L1 and VEGF-A. Biotheus will receive an upfront payment of $55 million, with the rest coming as development and sales milestones are reached. PM8002 is being assessed in a phase II/III study in China to evaluate its safety and efficacy as a monotherapy and in combination with chemotherapy in patients with non–small cell lung cancer.

• The FDA revised an existing indication for pembrolizumab (Keytruda; Merck) used with trastuzumab, fluoropyrimidine, and platinum-containing chemotherapy for the first-line treatment of patients with locally advanced inoperable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma. The updated indication restricts its use to patients whose tumors express PD-L1. The agency also approved the Agilent PD-L1 IHC22C3 pharmDX as a companion diagnostic to determine which patients with gastric/GEJ cancers are eligible to receive the pembrolizumab regimen.
• The pharmaceutical company Accord Healthcare resumed production and distribution of methotrexate, the FDA reported. One of the most prescribed cancer drugs, methotrexate is an injectable chemotherapeutic used to treat acute lymphoblastic leukemia, breast cancer, lung cancer, and other types of malignancies. The drug has been in short supply since March.
• Cancer Research UK (CRUK) and the KWF Dutch Cancer Society announced a partnership "to advance promising therapeutic agents for cancer through early clinical development" through CRUK’s Center for Drug Development with funding from KWF. According to CRUK, "the alliance will focus on projects featuring a novel, promising, academic-derived agent which has the potential to address a high unmet clinical need. Typically, these agents are ready for the next step in development or have had their development stalled or delayed due to a lack of funding or resources."

• Overall tobacco use among high school students dropped between 2022 and 2023—from 16.5% to 12.6%, according to the 2023 National Youth Tobacco Survey (available at www.cdc.gov/mmwr). The decline was primarily attributed to reduced use of electronic cigarettes—from 14.1% to 10%. However, 6.6% of middle school students reported using tobacco products, up from 4.5%.
• The American Cancer Society issued new guidelines for lung cancer screening that will make nearly 5 million more people eligible for a yearly low-dose computed tomography scan (CA Cancer J Clin [Epub ahead of print]). People ages 50 to 80—no longer ages 55 to 74—should discuss screening with their health care provider if they currently smoke or used to smoke and have a history of smoking of 20-pack-years or more—no longer 30-pack-years. Further, for those who quit smoking, screening should not stop after 15 years; rather it should continue yearly for anyone with at least a 20-pack-year history.
• The FDA approved pembrolizumab plus chemotherapy for some biliary tract cancers. Efficacy of the regimen was demonstrated in the KEYNOTE-966 trial, which involved 1,069 patients with locally advanced inoperable or metastatic disease who hadn’t received prior systemic therapy for advanced disease. The combination of the PD-1 inhibitor (Keytruda; Merck) with gemcitabine and cisplatin demonstrated a 17% improvement in overall survival (OS) compared with chemotherapy alone. The median OS was 12.7 months and 10.9 months, respectively.

• Coherus BioSciences announced that the FDA also approved the PD-1 inhibitor toripalimab (Loqtorz) plus chemotherapy for metastatic or recurrent locally advanced nasopharyngeal carcinoma, as well as for single agent treatment for adults with recurrent inoperable or metastatic disease that has advanced on or after receiving a platinum-containing chemotherapy. For the first indication, the approval was based on the JUPITER-02 trial, which found a significant improvement in OS—median OS was not reached in the toripalimab arm but was 33.7 months in the chemotherapy alone arm. For the second indication, the POLARIS-02 trial demonstrated an overall response rate of 21% and a median duration of response of 14.9 months.
• Mersana Therapeutics reported that the FDA lifted a clinical hold on its phase I clinical trial of XMT-2056, a STING-agonist antibody–drug conjugate designed to treat patients with HER2-high or HER2-low tumors as a monotherapy and in combination with standard-of-care agents. Based on safety data from patients already enrolled in the trial, the starting dose for the drug was lowered. The trial is investigating XMT-2056 in patients who have already received treatment for advanced and recurrent solid tumors expressing HER2, including breast, gastric, colorectal, and non–small cell lung cancers.

• Based on data presented at the 2023 ESMO Congress in Madrid, Spain, October 20–24, standard care for untreated inoperable or metastatic urothelial carcinoma (mUC) will likely change. In the EV-302/KEYNOTE-A39 trial, the nectin-4 antibody–drug conjugate enfortumab vedotin (Padcev; Astellas/Seagen) combined with the PD-1 inhibitor pembrolizumab (Merck) was compared with standard chemotherapy. At a median follow-up of 17.2 months, enfortumab vedotin/pembrolizumab reduced the risk of disease progression or death by 55% compared with chemotherapy; median progression-free survival (PFS) was 12.5 months and 6.3 months, respectively, and the overall survival (OS) was 31.5 months and 16.1 months, respectively. The findings, the first ever reported to show improved survival over chemotherapy as first-line treatment for mUC, were met with a standing ovation.
• Another trial presented at the ESMO Congress and simultaneously published, CheckMate-901, demonstrated improved survival in patients with newly diagnosed mUC as well (N Engl J Med 2023 Oct 22 [Epub ahead of print]). Here, the PD-1 inhibitor nivolumab (Opdivo; Bristol Myers Squibb) plus chemotherapy was compared with chemotherapy alone. At a median follow-up of 33.6 months, the median OS in the nivolumab cohort was 21.7 months and 18.9 months in the chemotherapy only cohort. The median duration of complete response (CR) was 37.1 months and 13.2 months, respectively.
• Genentech’s alectinib (Alecensa) reduced the risk of disease recurrence or death by 76% in people with ALK-positive early-stage lung cancer compared with platinum-based chemotherapy, according to data from the phase III ALINA trial presented at the ESMO Congress. Median disease-free survival (DFS) was not reached in patients who received the ALK inhibitor compared with 41.3 months in those who received chemotherapy. People diagnosed with ALK-positive lung cancer are generally younger—around age 55—and at higher risk of developing brain metastases, so the improvement in central nervous system DFS was welcome news.
• For patients with newly diagnosed EGFR exon 20 insertion–mutated advanced non–small cell lung cancer (NSCLC), the combination of amivantamab (Rybrevant; Janssen) plus chemotherapy significantly improved PFS compared with chemotherapy alone, researchers reported at the conference; data were simultaneously published (N Engl J Med 2023 Oct 21 [Epub ahead of print]). In the phase III PAPILLON trial, patients who received the bispecific antibody and chemotherapy had a 60% reduction in the risk of disease progression or death. The PFS was 11.4 months for the combination and 6.7 months for the monotherapy, suggesting that amivantamab should be a new standard of care, researchers said.
• Also presented at the ESMO meeting and simultaneously published: Among 802 patients with operable NSCLC receiving AstraZeneca’s durvalumab (Imfinzi) plus platinum-based chemotherapy or placebo prior to surgery, followed by adjuvant durvalumab or placebo, event-free survival (EFS) was significantly longer in the durvalumab arm (N Engl J Med 2023 Oct 23 [Epub ahead of print]). After 12 months, EFS was observed in 73.4% of patients compared with 64.5% of those who received placebo. Pathologic CR was also higher—17.2% vs. 4.3%, respectively.
• Researchers at ESMO reported that, based on data from a phase III trial, the OS benefit of tebentafusp (Kimmtrak) for patients with uveal melanoma continues after 3 years; the findings were concurrently published (N Engl J Med 2023 Oct 21 [Epub ahead of print]). A bispecific T-cell receptor molecule that targets glycoprotein 100 and CD3 made by Immunocore, tebentafusp yielded a median OS of 21.6 months compared with 16.9 months in the control group; researchers estimate that 27% of the patients who received tebentafusp were alive at 3 years, compared with 18% in the control group.

• Also at ESMO and concurrently published, researchers reported that combining Amgen’s KRAS^G12C inhibitor sotorasib (Lumakras) and EGFR inhibitor panitumumab (Vectibix) may be more effective at treating metastatic KRAS^G12C-mutant colorectal cancer than sotorasib alone (N Engl J Med 2023 Oct 23 [Epub ahead of print]). In a phase III trial, patients with chemorefractory metastatic disease who had not already taken a KRAS^G12C inhibitor received either 960 mg or 240 mg of sotorasib plus panitumumab daily or investigator’s choice of trifluridine–tipiracil or regorafenib. After a median follow-up of 7.8 months, the median PFS was 5.6 months and 3.9 months, respectively, in the sotorasib arms, compared with 2.2 months in the investigator’s choice group.

• In other news:

  The FDA granted accelerated approval to entrectinib (Rozlytrek; Genentech) for children older than 1 month who have solid tumors with an NTRK gene fusion without a known resistance mutation, have metastatic disease or tumors for which surgery will likely cause severe morbidity, and whose disease has progressed despite an earlier treatment or has no satisfactory standard therapy. In a single-arm trial involving 33 patients, the overall response rate was 70% and the median duration of response (DoR) was 25.4 months. The most common cancers were primary central nervous system tumors and infantile fibrosarcoma.
• The agency also approved ivosidenib (Tibsovo; Servier Pharmaceuticals) for adults with relapsed or refractory myelodysplastic syndromes (MDS) with an IDH1 mutation as detected by an FDA-approved test; the FDA also approved the Abbott RealTime IDH1 Assay for this purpose. The decision was based on the single arm trial AG120-C-001, which enrolled 18 patients. Of the seven patients who responded, all were CRs—and responses occurred within a median of 1.9 months. The median DoR could not yet be estimated.
• Immunotherapy pioneer Steven Rosenberg, MD, PhD, of the NCI, was awarded the National Medal of Technology and Innovation, the nation’s highest honor for technologic achievement, by President Joe Biden. Among his accomplishments, Rosenberg identified the anticancer properties of IL2, the first cancer immunotherapy approved by the FDA; identified tumor-infiltrating lymphocytes and developed adoptive cell transfer; and was the first to use chimeric antigen receptor T cells to treat patients with aggressive lymphomas.
• The nomination of Monica Bertagnolli, MD, to be director of the NIH moved forward—it was approved by the U.S. Senate Committee on Health, Education, Labor, and Pensions by a vote of 15–6. The full Senate must now vote in favor of confirming her before she can assume the role; a date for the vote has not been set. Bertagnolli is currently the director of the NCI.

• NCI Director Monica Bertagnolli, MD, testified at her confirmation hearing to become the director of the NIH before the Senate Committee on Health, Education, Labor and Pensions, which will vote on her nomination on October 25. President Joe Biden announced in May that Bertagnolli was his choice for the role, but the full Senate must approve his pick. Under Bertagnolli’s leadership, the NCI issued the National Cancer Plan, which outlined strategic priorities to prevent disease, reduce the cancer death rate, and improve the lives of cancer survivors.
• Merck announced that it will pay $5.5 billion to Daiichi Sankyo to jointly develop and commercialize three of its investigational antibody–drug conjugates (ADC), a deal that could fetch $16.5 billion more if certain sales milestones are met. The ADCs, which could treat patients with a variety of cancer types either alone or in combination with other treatments, are patritumab deruxtecan, ifinatamab deruxtecan, and raludotatug deruxtecan, which are currently under study in non–small cell lung cancer (NSCLC), small cell lung cancer, and ovarian cancer, respectively. Updated results of the raludotatug deruxtecan trial will be presented at the 2023 ESMO Congress, October 20–24.
• Merck also announced that the FDA approved pembrolizumab (Keytruda) for certain cases of NSCLC. The agency OK'd the PD-1 inhibitor in combination with platinum-containing chemotherapy as a neoadjuvant treatment with single-agent pembrolizumab following surgery based on results of the KEYNOTE-671 trial. The median overall survival (OS) for patients who received this regimen was not reached, but for those who received a placebo, the median OS was 52.4 months.

• A clinical practice guideline on immunotherapy for the treatment of melanomas was issued by the Society for Immunotherapy of Cancer (J Immunother Cancer 2023;11:e006947). The guideline, which covers both common and rare subtypes of the disease, was developed by a panel of experts that drew upon published data and clinical experience. Among other things, it covers therapy selection, the management of patients with brain metastases, evaluation of treatment response, and quality of life.
• Researchers reported that enzalutamide plus androgen-deprivation therapy (leuprolide) as well as enzalutamide alone are more effective at prolonging survival than leuprolide monotherapy in patients at risk of prostate cancer progression due to high-risk biochemical recurrence—a prostate-specific antigen doubling time of 9 months or less (N Engl J Med 2023;389:1453–65). After 5 years, metastasis-free survival was 87.3%, 80%, and 71.4%, respectively. There was no substantial difference between the groups in reported quality of life.

• Bristol Myers Squibb announced it will acquire Mirati Therapeutics in a deal worth up to $5.8 billion. Mirati’s portfolio of drugs includes adagrasib (Krazati), approved for patients with KRAS^G12C-mutant non–small cell lung cancer (NSCLC); the selective PRMT5/MTA inhibitor MRTX1719, which has shown effectiveness against NSCLC, cholangiocarcinoma, and melanoma; MRTX1133, which is in development for certain cancers with KRAS^G12D mutations; and MRTX0902, a SOS1 inhibitor that could be used with other agents targeting the MAPK/RAS pathway.
• To better understand the digital health technologies (DHT) landscape and its myriad complexities, the FDA will create a new Digital Health Advisory Committee, with plans to be operational by 2024. DHTs include artificial intelligence/machine learning, augmented/virtual reality, wearables, as well as issues related to patient-generated health data and cybersecurity; the agency will solicit the committee’s technical and scientific expertise to ensure that the development of new DHTs is appropriately regulated without hampering innovation. A core of nine voting members will be chosen; those interested in serving or in nominating a candidate can do so electronically or by mail.
• Dual BRAF–MEK blockade got a new indication: The FDA OK’d encorafenib (Braftovi) and binimetinib (Mektovi), both Pfizer drugs, for patients with metastatic BRAF^V600E NSCLC. The BRAF and MEK inhibitor combination has been approved since 2018 for inoperable or metastatic BRAF^V600E/K melanoma. The label expansion nod was based on findings from PHAROS, a phase II trial, which showed an objective response rate (ORR) of 75% among 59 previously untreated patients; in another cohort of 39 patients receiving encorafenib–binimetinib as second-line therapy, the ORR was 46%.

• Brisbane, CA–based Tempest Therapeutics reported that adding a PPAR⍺ antagonist to standard care for inoperable or metastatic hepatocellular carcinoma may be a superior first-line strategy. According to the latest results from an ongoing phase Ib/II trial, among 70 patients randomly assigned to receive TPST-1120, Tempest’s experimental PPAR⍺ agent, with standard atezolizumab (Tecentriq; Roche) and bevacizumab, or just atezolizumab–bevacizumab, the ORRs were 30% vs. 13.3%, respectively. Progression-free and overall survival data also appear to be trending in favor of triplet therapy; further findings will be presented at an upcoming medical meeting, the company said in a press release.
• BioNTech and MediLink Therapeutics inked a deal to develop an antibody–drug conjugate (ADC) targeting HER3. The German company will pay the Suzhou, China–based biotech $70 million up front for exclusive global rights—other than in mainland China, Hong Kong, and Macau—to one of MediLink’s early-stage ADC assets; further milestone payments could potentially total more than $1 billion. With this deal, BioNTech is wading into an increasingly crowded HER3 ADC space dominated primarily by Daiichi Sankyo, which recently reported positive phase II data on its candidate, patritumab deruxtecan, in patients with EGFR-mutant NSCLC and plans to file for FDA approval in coming months.

• Takeda announced that mobocertinib (Exkivity) will be voluntarily withdrawn from the market in the United States because it did not meet its primary endpoint of improved progression-free survival (PFS) in a phase III trial involving patients with EGFR exon 20 insertion mutation–positive non–small cell lung cancer whose disease advanced after platinum-based chemotherapy. The drug had received accelerated approval based on the results of a phase I/II trial, but Takeda needed to confirm those findings in this larger study. The company will also withdraw the drug in other countries where it’s approved.
• Lilly announced that it will spend $1.4 billion to acquire POINT, a radiopharmaceutical company developing radioligand therapies—radioisotopes attached to a targeting molecule that can deliver radiation directly to cells—to treat cancer. POINT’s most advanced investigational agent is PNT2002, a PSMA-targeted radioligand therapy for patients with metastatic castration-resistant prostate cancer; top-line study results are expected this year. POINT has also developed PNT2003, a somatostatin receptor–targeted radioligand to treat patients with gastroenteropancreatic neuroendocrine tumors.
• The Appellate Division of the Superior Court of New Jersey threw out a $223.8 million verdict against Johnson & Johnson, arguing that a lower court should not have allowed some scientific testimony from experts for the plaintiff. That sum had been awarded to four plaintiffs who alleged that the company’s talc-based products, such as its baby powder, contained asbestos that caused their cancers. However, a three-judge panel said that three experts "had not explained the facts or methods they used to support their opinions that the plaintiffs got cancer from being exposed to asbestos," according to Reuters, and called for a new trial.

• Based on the recommendation of an independent data monitoring committee, Syndax Pharmaceuticals announced that it will bring an early halt to a phase I/II trial of revumenib, a first-in-class menin inhibitor, in patients with relapsed/refractory (r/r) KMT2A-rearranged acute myeloid leukemia and acute lymphoid leukemia. Among 57 evaluable patients in the AUGMENT-101 trial, 23% experienced a complete remission (CR) and a CR with partial hematologic recovery, with a median duration of response hitting 6.4 months. The company said it will file for FDA approval later this year.
• AbbVie announced that the combination of venetoclax (Venclexta) and dexamethasone did not significantly improve PFS compared with pomalidomide and dexamethasone, the primary endpoint of the phase III CANOVA study, in 263 patients with t(11;14)-positive r/r multiple myeloma. Venetoclax, a BCL-2 inhibitor, yielded a PFS of 9.9 months vs. 5.8 months for the pomalidomide arm and a P value of 0.237. However, the overall response rate and the rate of very good partial response or better were statistically significant; median overall survival was 32.4 months vs. 24.5 months, respectively, with a P value of 0.067. Given the favorable trends, the company said it will discuss the results and potential next steps with regulatory authorities.

• Bosutinib’s (Bosulif; Pfizer) label expanded to include pediatric chronic myelogenous leukemia. The BCR–ABL and Src tyrosine kinase inhibitor (TKI) received the FDA’s go-ahead as a treatment option for patients age 1 and older with chronic phase Philadelphia chromosome–positive disease, either newly diagnosed or relapsed/refractory. Data from BCHILD, a phase I/II study, provided the basis for this approval, and the agency also OK’d a new capsule form of bosutinib in 50 mg and 100 mg dosages.
• Gilead pulled the plug on evaluating magrolimab in TP53-mutant acute myeloid leukemia (AML). The company concluded that its investigational CD47 inhibitor was unlikely to demonstrate a survival benefit, compared with standard care, for patients enrolled in the phase III ENHANCE-2 trial. This decision comes on the heels of the FDA’s partial clinical hold, placed last month, on studies of magrolimab in AML; back in July, Gilead also nixed assessing the drug with or without azacitidine for patients with higher-risk myelodysplastic syndromes in the ENHANCE study.
• The federal Advanced Research Projects Agency for Health (ARPA-H), part of the NIH, announced that Massachusetts will host ARPA-H’s Investor Catalyst hub. Hadley, MA–based nonprofit VentureWell has been selected to run this hub, which will be located in Boston and, according to a press release, "focus on helping ARPA-H programs navigate the complexities of the business and regulatory landscape." Besides the Boston hub, two others will anchor the agency’s newly launched national health innovation network, ARPANET-H: Dallas, TX, will host the Customer Experience hub, and a final site for the Stakeholder and Operations hub is expected to be named later in 2023.

• According to top-level findings from MARIPOSA, a phase III trial, a Janssen duo, lazertinib (Leclaza) and amivantamab (Rybrevant), looks effective in previously untreated EGFR-mutant non–small cell lung cancer. Compared with standard osimertinib (Tagrisso; AstraZeneca), patients randomly assigned to receive this combination of a third-generation TKI and an EGFR–MET bispecific antibody experienced a statistically significant, clinically meaningful improvement in progression-free survival, with overall survival also trending in favor of lazertinib–amivantamab. MARIPOSA’s data will be submitted for presentation at an upcoming meeting, Janssen said in a press release.
• After a strategic focus revamp, AbbVie axed its chimeric antigen receptor (CAR) T-cell therapy deal with Caribou Biosciences. Back in 2021, AbbVie paid $30 million up front and further invested $10 million to collaborate on two of the Berkeley, CA–based biotech’s allogeneic CAR products targeting CD19 and BCMA, which are both in the clinic. This partnership termination is AbbVie’s third in the last 2 weeks; the company also just ended codevelopment of I-Mab’s lemzoparlimab, another CD47 inhibitor, besides recently dropping Harpoon Therapeutics’ anti-BCMA trispecific T-cell engager, HPN217.

• The 2023 Albert Lasker Basic Medical Research Award went to Google DeepMind’s Demis Hassabis, PhD, and John Jumper, PhD. They will share a $250,000 prize for inventing AlphaFold, a machine-learning artificial intelligence technology that predicts 3D protein structures. The latest iteration, AlphaFold2, provides atomically precise prognostications within minutes and has already produced data, which are open access, on structures of almost all the proteins (roughly 200 million) in organisms whose genomes have been sequenced.
• BeiGene’s tislelizumab (Tevimbra) became the first Chinese PD-1 inhibitor to advance in Europe and in the United States. The European Commission greenlighted tislelizumab as a second-line option for adult patients with inoperable advanced esophageal squamous cell carcinoma, and it will undergo FDA review as first-line treatment for this disease. BeiGene also regained full global rights to tislelizumab, with Novartis—after reassessing its strategy in the PD-1 inhibitor space—ending a joint development deal for which it had paid $650 million in 2021.
• The FDA issued new draft guidance for companies seeking drug approval based on a single trial and confirmatory evidence. Early communication with regulators is key, and for an adequate, well-controlled study that’s "highly persuasive," a "lesser quantity of confirmatory evidence" may be possible, the agency said; meanwhile, "less persuasive" trials may require more corroborative data to support a conclusion of effectiveness. The guidance is open for comments until December 18.

• According to top-level findings from TROPION-Breast01, a phase III trial, datopotamab deruxtecan (Dato-DXd; AstraZeneca/Daiichi Sankyo) is an effective second-line treatment for metastatic hormone receptor–positive, HER2-low or HER2-negative breast cancer. Patients randomly assigned to receive the investigational TROP2-targeting antibody–drug conjugate instead of chemotherapy experienced a statistically significant, clinically meaningful improvement in progression-free survival, with overall survival trending in the right direction. TROPION-Breast01’s data will be presented at an upcoming meeting and shared with the FDA, AstraZeneca said in a press release.
• Patients with myelofibrosis (MF) got a new JAK1/2 inhibitor, with the FDA approving momelotinib (Ojjaara; GSK) for newly diagnosed and previously treated disease alike. The drug also blocks ACVR1, which decreases circulating hepcidin and thereby mitigates anemia, a major complication of MF that often leads to patients discontinuing treatment and requiring transfusions. The agency’s decision was based on data from two phase III trials, MOMENTUM and SIMPLIFY-1, that demonstrated momelotinib’s superiority over danazol, a synthetic steroid prescribed for MF-associated symptoms, and ruxolitinib (Jakafi; Incyte), an older JAK1/2 inhibitor.

• President Joe Biden’s Cancer Cabinet met to present and discuss new Cancer Moonshot initiatives aimed at halving the death rate from cancer by 2047. The announcements included word of $240 million investment from the Advanced Research Projects Agency for Health (ARPA-H) to accelerate innovative projects to prevent, detect, treat, and survive cancer; a program to pioneer technologies to make data more readily accessible; a nationwide network to bring cancer clinical trials to underserved communities; and an expansion of efforts to prevent smoking and increase smoking cessation.
• Two cancer researchers will receive part of a $15 million prize for their work on chimeric antigen receptors (CAR), which rev up T-cell activity against cancer. Carl June, MD, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, and Michel Sadelain, MD, PhD, of Memorial Sloan Cancer Center in New York, NY, will split the award with nine other winners of the Breakthrough Prizes in Life Sciences, Fundamental Physics, and Mathematics. The Breakthrough Prize Foundation has conferred the awards, dubbed the Oscars of Science, for the past 13 years.
• The American Association for Cancer Research (AACR) announced the formation of the AACR Cancer Centers Alliance, which will "bring together the nation’s cancer centers with the goal of markedly expanding the scope and impact of these world-class institutions for the benefit of all patients across geographies and diverse populations." The initiative will "accelerate the pace of discovery by providing an ongoing mechanism for transferring new knowledge, sharing resources, developing national demonstration projects, and driving innovation that impacts cancer science, cancer care delivery, and science and health policy." The Alliance’s initial plans were also released (Cancer Discov 2023 Sep 13 [Epub ahead of print]).

• As well, the AACR issued its 13th annual Cancer Progress Report, available at https://cancerprogressreport.aacr.org. In addition to providing the latest statistics on cancer incidence and mortality, the 2023 report "offers detailed updates and important context regarding the latest research in cancer etiology, early detection, diagnosis, treatment, prevention, and survivorship;" shines a spotlight on immunotherapy, challenges facing cancer research and patient care, and cancer disparities; and calls upon the U.S. Congress to provide predictable, robust, and sustained funding for the NIH and the NCI.
• The FDA approved new and updated indications for temozolomide chemotherapy—namely for the adjuvant treatment of adults with newly diagnosed anaplastic astrocytoma and for treatment of adults with refractory anaplastic astrocytoma; its approved use with radiotherapy for adults with newly diagnosed glioblastoma and then as a maintenance treatment has not changed. The action was taken through the Project Renewal initiative, which engages experts to review existing evidence and "update labeling information for older oncology drugs to ensure information is clinically meaningful and scientifically up-to-date."

• Astellas Pharma withdrew a lawsuit against the U.S. Department of Health and Human Services, filed in July, seeking to block price negotiations that were called for as part of 2022’s Inflation Reduction Act (IRA). In late August, the government named the first 10 drugs that will be subject to price negotiations; the company’s prostate cancer drug, enzalutamide (Xtandi), did not make the list, although business analysts had predicted that it would. "However, our decision to withdraw the case does not change our fundamental belief that in its current form, the Medicare Drug Price Negotiation Program created by the IRA is bad policy and unconstitutional," the company said.
• Reuters reported that Blue Cross Blue Shield of Louisiana filed a lawsuit against Bristol Myers Squibb (BMS) alleging that Celgene, now owned by BMS, relied on fraudulently obtained patents to prevent competition from generic versions of pomalidomide (Pomalyst) since October 2020, causing insurers to overpay "by many hundreds of millions, if not billions, of dollars." The suit claims that BMS applied for patents based on information already in the public domain and then filed lawsuits against companies that tried to market generic versions of the thalidomide analogue for the treatment of multiple myeloma.
• Based on data from a phase III study of the human papillomavirus (HPV) vaccine Gardasil 9 (Merck) in 1,272 girls and boys ages 9–15, researchers found that none of the participants had developed HPV-related high-grade disease, certain cancers, or genital warts in the 10 years following the three-dose vaccine (Pediatrics 2023 Sep 5 [Epub ahead of print]). Gardasil 9 is approved for people ages 9–45 for the prevention of cervical, vulvar, vaginal, anal, oropharyngeal, and other head and neck cancers caused by nine types of HPV, as well as precancerous lesions and genital warts. HPV types 16, 18, 31, 33, 45, 52, and 58 cause about 80% of cervical cancers.

• In a study of 266 men who had a radical prostatectomy, 20% had testosterone levels at least twice as high in blood vessels around the prostate than in peripheral blood—countering the assumption that a routine blood test accurately measures the hormone in all parts of the body—perhaps because a vessel between the testes and the prostate bypasses peripheral circulation, allowing this "sneaky testosterone" to reach the gland (J Clin Invest 2023;133:e17117). The finding may explain why men with elevated exposure to testosterone, which can play a role in prostate cancer development and progression, fared worse following surgery than those who didn’t have greater levels of testosterone.
• Based on interim data from the phase III innovaTV 301 trial, Seagen and Genmab announced that tisotumab vedotin (Tivdak) met its primary endpoint of improved overall survival compared with chemotherapy alone in patients with recurrent or metastatic cervical cancer who had already tried another therapy. Statistically significant improvements in progression-free survival and objective response rate were also noted. Tisotumab vedotin, an antibody–drug conjugate that targets Tissue Factor protein on cervical cancer cells, was granted accelerated approval by the FDA in 2021; the innovaTV 301 trial is the pivotal confirmatory trial conducted to gain full approval.

• A BTK inhibitor made by Pharmacyclics/Janssen Biotech, ibrutinib (Imbruvica) was selected as one of 10 drugs chosen for price negotiations by the U.S. Centers for Medicare & Medicaid Services (CMS); the call for price negotiations was stipulated as part of the Inflation Reduction Act (IRA) of 2022. The drugs that were selected, most of which treat diabetes or cardiovascular disease, had the highest total covered prescription costs between June 1, 2022, and May 31, 2023, accounting for $50.5 billion—or 20%—of gross Medicare Part D–covered costs, according to the CMS. The only cancer drug on the list, ibrutinib treats blood cancers.
• AstraZeneca filed a legal challenge to the drug price negotiation provisions of the IRA, arguing that the provisions "run headlong into the goals of the Orphan Drug Act, a federal statute designed to encourage manufacturers to invest in new therapies for rare diseases," creating disincentives to develop them. The company noted that its PARP inhibitor olaparib (Lynparza), which is not on the list for price negotiation, was approved in 2014 for a small subset of patients with ovarian cancer. Had the IRA been in effect at that time, the company might not have developed it—meaning that subsequent approvals for certain patients with breast, pancreatic, and prostate cancer might never have happened.
• Novartis announced that it will discontinue the development of NIS793, an investigational anti-TGFβ monoclonal antibody that it had licensed from XOMA in 2015. Clinical trials of NIS793 will stop enrolling patients, and Novartis will collect data from the trials and return the drug to XOMA. The agent had received orphan drug designation from the FDA in 2021 for the treatment of pancreatic cancer, but its safety and efficacy have not been established and it might never be approved.

• The FDA expanded the indication for luspatercept (Reblozyl; Bristol Myers Squibb) to include first-line treatment for anemia in adults with very low- to intermediate-risk myelodysplastic syndromes who have not received erythropoiesis-stimulating agents (ESA) and may need regular transfusions of red blood cells (RBC). The decision was based on the phase III COMMANDS trial, in which luspatercept showed greater efficacy of concurrent RBC transfusion independence and increases in hemoglobin compared with epoetin alfa, an ESA.
• Based on a meta-analysis of 18 long-running clinical trials involving more than 2 million people, colorectal cancer screening with sigmoidoscopy can extend life by about 3 months, researchers reported, but other screening tests—fecal testing and mammography—do not seem to increase longevity (JAMA Intern Med 2023 Aug 28 [Epub ahead of print]). Prostate-specific antigen testing increased longevity by 37 days, and lung cancer screening using CT extended life by 107 days, but these "estimates are uncertain." The researchers say they aren’t in favor of abandoning screening but suggest that the potential benefits and harms of screening be more clearly conveyed to patients.

• The phase III CABINET trial of cabozantinib (Cabometyx; Exelixis) was unblinded and stopped early after an independent Data and Safety Monitoring Board found that the multi–tyrosine kinase inhibitor substantially prolonged time without disease progression or death in patients with pancreatic cancer. The placebo-controlled trial enrolled 290 patients with either advanced pancreatic neuroendocrine tumors or advanced extrapancreatic neuroendocrine tumors, which are often called carcinoid tumors, after their disease advanced despite receiving a systemic therapy. Additional details will be presented at an upcoming medical meeting.
• Cabozantinib significantly prolonged progression-free survival in the phase III CONTACT-02 study, which is assessing the drug combined with the PD-L1 inhibitor atezolizumab (Tecentriq; Roche) in patients with metastatic castration-resistant prostate cancer, according to interim data. The regimen elicited only a "trend toward improvement" in overall survival, but the trial will continue to collect this data. The companies said that they will present their findings at an upcoming medical conference.
• Roche inadvertently released data from an interim analysis of a trial assessing tiragolumab in patients with lung cancer. An anti-TIGIT immunotherapeutic, the drug led to a 19% reduction in mortality compared with patients who didn’t receive it, a result that is not yet statistically significant according to the company. Researchers will continue to gather data from the trial and report longer-term survival results in 2024.

• Based on a meta-analysis of nearly 45,000 men in 35 countries, researchers estimate that 31% of men globally are infected with at least one type of genital human papillomavirus (HPV)—and that 20% carry at least one strain of HPV linked to a high risk of cancer, most commonly HPV-16 and HPV-6; 12 of more than 200 types of HPV are oncogenic (Lancet Glob Health 2023;11:e1345–62). The prevalence was highest among men ages 25–29. Researchers say that the findings call for a greater emphasis on HPV prevention among boys and men, particularly through vaccination.
• Gilead Sciences announced that the FDA placed a partial clinical hold on U.S. studies evaluating magrolimab to treat acute myeloid leukemia (AML). Patients already enrolled in AML studies of magrolimab may continue to receive the potential first-in-class investigational anti-CD47 immunotherapeutic. Studies of magrolimab in solid tumors—head and neck cancers and colorectal, lung, and breast cancers—are not affected by the hold.
• The Biden Cancer Moonshot announced the launch of CUREIT, a project to develop generalizable mRNA platforms to train the immune system to fight cancer and other diseases more effectively. The goal of CUREIT is to create a toolbox of mRNA and related technologies to boost "helpful" immune responses, such as prompting immune cells to target and attack tumors. CUREIT will be led by a team at Emory University in Atlanta, GA, with up to $24 million from the Advanced Research Projects Agency for Health (ARPA-H), which was established to drive breakthroughs in the prevention, detection, and treatment of cancer and other diseases.

• YouTube announced that it will remove "egregiously harmful" medical content from its site, particularly misinformation about cancer prevention and treatment, as well as material that contradicts health authority guidance. For example, the company says that a video claiming that garlic cures cancer would be taken down. To increase the amount of high-quality content on the site, YouTube will create cancer-related videos with authoritative sources and collaborate with the Mayo Clinic in Rochester, MN, on videos tied to a variety of cancers.
• The FDA formally placed a clinical hold on the phase I PLAT-08 study of SC-DARIC33 (2seventy bio), a chimeric antigen T-cell receptor (CART) for the treatment of acute myeloid leukemia. The study, which the company had been conducting with Seattle Children’s Hospital in Washington, was paused in June after the death of a patient in the trial. Following an investigation, 2seventy and Seattle Children’s will amend the protocol in the hope of restarting the study as soon as possible.
• The FDA approved the combination of niraparib and abiraterone acetate (Akeega; Janssen) with prednisone to treat men with known or suspected deleterious BRCA-mutated, castration-resistant prostate cancer. The decision was based on results of the MAGNITUDE trial, which found a significant improvement in radiographic progression-free survival compared with abiraterone acetate and prednisone—16.6 months vs. 10.9 months, respectively. An exploratory overall survival (OS) analysis favored the niraparib arm—the median OS was 30.4 months vs. 28.6 months. Niraparib (Zejula; GSK) is a PARP inhibitor; abiraterone acetate (Zytiga; Janssen) is an androgen inhibitor.
• Arcellx announced that the FDA lifted a partial clinical hold on the phase II iMMagine-1 trial of CART-ddBCMA, an investigational drug for the treatment of relapsed/refractory multiple myeloma (MM). The hold was implemented in June following the death of a study patient who was "ineligible for the treatment under the trial protocol and was subsequently managed in a way that conflicted with that protocol." The trial protocol has been updated and more information about managing adverse events added.

• Speaking of MM, the FDA granted accelerated approval to elranatamab (Elrexfio; Pfizer) for the treatment of adults with relapsed/refractory disease who have received at least four prior therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. The decision was based on results from the phase II MagnetisMM-3 clinical trial, in which 97 patients who had not received BCMA-directed treatment experienced an overall response rate of 57.7% during a median follow-up of 11.1 months. Elranatamab is a BCMA-directed CD3 T-cell engager.
• ALX Oncology discontinued its ASPEN-02 and ASPEN-05 studies of evorpacept plus azacitidine compared with azacitidine alone in myelodysplastic syndromes and acute myeloid leukemia, respectively. The company said that the decision was based on data showing that the combination "did not substantially improve upon the historical activity of azacitidine alone." Evorpacept is an anti-CD47 agent.
• The FDA approved the melphalan-containing Hepzato Kit (Delcath Systems) as a liver-directed treatment for adults with uveal melanoma with inoperable hepatic metastases that affect less than 50% of the liver. The approval was based on the single-arm FOCUS study, in which the overall response rate in 91 patients was 36.3% and the median duration of response was 14 months. The drug is infused into the hepatic artery using the kit’s delivery system.
• The University of Texas (UT) at Austin and The MD Anderson Cancer Center in Houston will partner to build a new hospital at a cost of $2.5 billion. The facility, which will be in Austin, will further expand MD Anderson’s reach beyond Houston. The facility will have two medical towers, one of which will be dedicated to cancer; the other will be dedicated to the new UT hospital.

• Galera Therapeutics said it will cut its workforce by 70% after the FDA refused to approve avasopasem to treat severe oral mucositis in patients with head and neck cancers. In a letter to the company, the FDA said that the results of the phase III ROMAN trial and supporting data from the GT-201 trial did not sufficiently demonstrate the drug’s safety and effectiveness and that an additional trial needs to be conducted. The company is looking for a partner or other alternative to continue development of avasopasem and rucosopasem, an agent that could boost the effectiveness of stereotactic body radiation for non–small cell lung cancer (NSCLC) and locally advanced pancreatic cancer.
• The FDA granted full, regular approval to pralsetinib (Gavreto; Blueprint Medicines/Genentech) to treat adults with metastatic RET fusion–positive NSCLC; accelerated approval for this indication was granted in 2020 based on data from 114 patients enrolled in the ARROW trial. The regular approval considered an additional 25 months of follow-up and 123 more patients. Of the 107 patients who had not been previously treated, the overall response rate (ORR) was 78% and the median duration of response (DOR) was 13.4 months; for those who had already been treated, the ORR and DOR were 63% and 38.8 months.
• Arcus Biosciences and Gilead Sciences announced that they will deprioritize development of etrumadenant for castration-resistant prostate cancer. Based on a recent analysis of radiographic progression-free survival in the ARC-6 phase Ib/II study, the A2a/A2b adenosine receptor agonist is not expected to demonstrate sufficient clinical benefit, although the trial will continue until its completion. Data from the ARC-9 trial evaluating etrumadenant as a treatment for metastatic colorectal cancer should be available before July 2024.

• Based on data from 18 prospective studies involving more than 300,000 adults in The Netherlands, the UK, Norway, and Canada, researchers concluded that depression and anxiety do not increase the risk of most cancers (Cancer 2023 Aug 7 [Epub ahead of print]). They found no association between depression or anxiety and cancer risk overall, and no association specifically for breast, prostate, and alcohol-related cancers after as long as 26 years. However, they did find a 6% higher risk of developing lung cancer and smoking-related cancers, although that was reduced after accounting for smoking, alcohol use, and body mass index. Researchers say that their findings support the importance of smoking cessation and other unhealthy behaviors that might develop as a result of depression or anxiety.
• Research from the American Cancer Society shows that substantial racial and ethnic disparities exist among people diagnosed with second primary cancers in the United States (JAMA Netw Open 2023;6:e2327429). They found that non-Hispanic Black patients with a second primary cancer had a 21% higher cancer-related death rate and a 41% higher cardiovascular-related death rate compared with white patients. Similarly, Hispanic patients experienced a 10% higher cancer-related death rate than non-Hispanic white patients, but their cardiovascular-related death rate was 10% lower. The disparities were due, in part, to second primary cancers being diagnosed at later stages in Hispanic and non-Hispanic Black patients.

• The FDA sent a warning letter to India’s Intas Pharmaceuticals spelling out "significant violations of current good manufacturing practice (CGMP) as well as destroyed and discarded data." The company was cited for numerous quality control issues by the FDA late last year, but in the letter, the agency states that the company’s attempts to address those CGMP failures have been inadequate and directs Intas to "correct any violations promptly." Intas supplies about half of the cisplatin and carboplatin used in the United States, and the current lack of imports has led to a shortage of these drugs.
• In a new guidance document, the American College of Physicians (ACP) recommends starting colorectal cancer screening at age 50 for asymptomatic, average-risk adults and stopping screening in such patients older than 75 or who have a life expectancy of 10 years or less. The ACP guidelines say that clinicians should consider not screening asymptomatic, average-risk adults ages 45–49, given the "uncertainty around benefits and harms of screening in this population." The United States Preventive Services Task Force, the American Cancer Society, and other groups say screening should start at 45 because the disease incidence is rising in people younger than 50.
• Taiho Oncology announced that the FDA approved trifluridine/tipiracil (Lonsurf) plus bevacizumab to treat patients with metastatic colorectal cancer who were previously treated with a chemotherapy regimen, a VEGF inhibitor, and an anti-EGFR therapy if they had a RAS wild-type mutation. The decision was based on findings from the phase III SUNLIGHT trial, in which patients who received trifluridine/tipiracil plus bevacizumab had a median overall survival of 10.8 months compared with 7.5 months for patients who received just trifluridine/tipiracil; progression-free survival (PFS) was 5.6 months and 2.4 months, respectively.

• The agency also approved the PD-1 inhibitor dostarlimab (Jemperli; GSK) to treat endometrial cancer that is mismatch repair–deficient (dMMR) or microsatellite instability–high (MSI-H). The approval was based on the phase III RUBY trial, which assessed the efficacy of dostarlimab plus carboplatin and paclitaxel versus chemotherapy and placebo in a subgroup of 122 patients with dMMR/MSI-H primary advanced or recurring endometrial cancer. PFS was 30.3 months among patients treated with dostarlimab plus chemotherapy compared with 7.7 months among patients who received chemotherapy and placebo.
• According to a just-published study (Nat Genet 2023 Jul 31 [Epub ahead of print]), a broader population of patients may benefit from PARP inhibitors—including those with a common form of breast cancer. The drugs are used to treat patients with breast, ovarian, and prostate cancer who have inherited BRCA1/2 mutations, but researchers have found that they may also be effective in treating patients with SF3B1 mutations, which have been tied to estrogen receptor–positive breast cancers and some leukemias and melanomas. Cells with an altered form of SF3B1 lack the protein CINP, which regulates the cancer cells’ response to PARP inhibitors, making them unable to copy their DNA.

• Thanks to the Biden Cancer Moonshot and the Advanced Research Projects Agency for Health (ARPA-H), surgeons might one day have novel technologies to help them remove cancerous tumors with greater precision and accuracy. Currently, doctors cannot easily and fully distinguish cancer cells from surrounding normal tissue in the operating room. ARPA-H was created to generate breakthroughs in the prevention, detection, and treatment of cancer and other diseases; developing this novel technology for surgeons is the first ARPA-H program focusing on cancer.
• Patients with inoperable, untreated hepatocellular carcinoma may soon have a new treatment option. In a randomized, phase III trial, researchers found that a combination of the PD-1 inhibitor camrelizumab (AiRuiKa; Jiangsu Hengrui Medicine) and the investigative VEGFR2-targeted tyrosine kinase inhibitor rivoceranib (apatinib; Aitan; Elevar Therapeutics) significantly extended progression-free survival (PFS) compared with the multikinase inhibitor sorafenib (Nexavar; Bayer)—after a median follow-up of 7.8 months, the median PFS was 5.6 months and 3.7 months, respectively. Overall survival also favored camrelizumab–rivoceranib over sorafenib—22.1 months vs. 15.2 months, respectively, after a median follow-up of 14.5 months.
• Gilead nixed work on the anti-CD47 antibody magrolimab (Forty Seven) with/without azacitidine (Vidaza; Bristol Myers Squibb) for the treatment of patients with higher-risk myelodysplastic syndromes due to the futility of the ENHANCE study. Gilead will proceed with two other phase III trials of magrolimab: ENHANCE-2 in acute myeloid leukemia (AML) with TP53 mutations and ENHANCE-3 in first-line AML. The company had made a $4.9 billion deal with Forty Seven to advance its CD47 candidates.

• The news was not all bad for Gilead because the European Commission approved sacituzumab govitecan (Trodelvy) to treat patients with inoperable or metastatic hormone receptor–positive, HER2-negative breast cancer who have already received endocrine therapy and at least two systemic therapies for advanced disease. The approval was based on findings of the phase III TROPiCS-02 study, in which sacituzumab govitecan demonstrated a significant and clinically meaningful overall survival benefit of 3.2 months compared with physician's choice of chemotherapy. The drug is also approved in Europe as a second-line therapy for triple-negative breast cancer.
• Exelixis settled a lawsuit against Teva Pharmaceuticals over patents on cabozantinib (Cabometyx); Teva had been seeking approval to market a generic version of the drug prior to the expiration of cabozantinib patents. Under the terms of the agreement, Exelixis will grant Teva a license to market its generic version of the drug beginning on January 1, 2031, if the drug is approved by the FDA. Both companies also agreed to end all ongoing litigation related to cabozantinib; additional details were not disclosed.
• SQZ Biotechnologies announced that Roche will not exercise its option to work with them on drugs based on mononuclear antigen-presenting cells (APC) for human papillomavirus 16–positive tumors. Fierce Biotech reported that Roche paid $45 million up front to SQZ in 2018 to use that company's Cell Squeeze platform, which "squeezes cells to make them present tumor antigens to the immune system." In a phase I study, a SQZ APC candidate was well tolerated and "provided a significant survival benefit to a subpopulation of patients with enhanced tumor T cell infiltration," SQZ said.

• Bloomberg reported that the FDA will allow the distribution of 10 more lots of cisplatin from China—made by Qilu Pharmaceutical—amid a nationwide shortage of the chemotherapeutic in the United States. In June, the agency approved the importation of four lots of cisplatin from the company, as well as carboplatin, which has also been in short supply. The shortages have led to rationing of the drug.
• Mirati Therapeutics reported that European regulators issued a negative opinion of adagrasib (Krazati) to treat KRAS^G12C-mutated advanced non–small cell lung cancer (NSCLC). According to Mirati, the European Medicine Agency's Committee for Medicinal Products for Human Use stated that adagrasib "has a positive risk-benefit profile, however, does not fulfill certain requirements for a Conditional Marketing Authorisation Application." Details related to the supposedly unfulfilled requirements weren't disclosed, but the company said it disagrees with the opinion and will ask that data be reexamined.
• The FDA approved quizartinib (Vanflyta; Daiichi Sankyo) to treat adults with newly diagnosed acute myeloid leukemia (AML) that's FLT3 internal tandem duplication–positive, as detected by an FDA-approved test. The decision was based on the results of the QuANTUM-First study, which involved 539 patients with this form of AML. The trial demonstrated a statistically significant improvement in overall survival with quizartinib plus standard therapy vs. standard therapy alone; the complete response (CR) rate was the same in both study arms, but the median duration of response was about three times longer with quizartinib.
• The European Commission granted conditional marketing authorization for glofitamab (Columvi; Roche) to treat adults with relapsed/refractory diffuse large B-cell lymphoma following at least two prior systemic therapies. Glofitamab is a CD20xCD3 T cell–engaging bispecific antibody given over a fixed period, as well as an off-the-shelf product, so patients do not have to wait for cell collection and genetic engineering of the cells—a benefit for those at high risk of disease progression. In a phase I/II trial involving 108 patients, 35% of them had a CR; the overall response rate was 50%.

• According to STAT, the European Union fined Illumina $475 million for finalizing its acquisition of GRAIL, a cancer diagnostics company, without clearing it with regulators. Illumina, a giant in the genetic sequencing market, has also been ordered by the U.S. Federal Trade Commission to divest itself of GRAIL, a ruling the company is appealing. Regulators have argued that the $8 billion acquisition could strangle competition.
• ADC Therapeutics paused enrollment in the phase II LOTIS-9 trial evaluating loncastuximab tesirine (Zynlonta) and rituximab in patients with newly diagnosed diffuse large B-cell lymphoma who are frail and not fit for treatment. A review of data from 40 trial participants revealed that seven died and five more developed respiratory problems—although 11 of the 12 respiratory-related events were "unlikely or unrelated to the study drug," according to researchers. All the patients who died had underlying respiratory conditions, such as chronic obstructive pulmonary disease and pulmonary edema.
• In a U.S. Securities and Exchange Commission filing, Novartis and BeiGene said that they have terminated their agreement to develop the TIGIT inhibitor ociperlimab, with BeiGene regaining global rights to the drug. Novartis said the decision was based on phase II trial data, risks and potential benefits, and other factors. Novartis will not move ahead with a phase III study in ociperlimab in NSCLC or a phase II study in triple-negative breast cancer.
• The NCI named its 72nd NCI-Designated Cancer Center: the University of Florida Health Cancer Center. The ranking indicates that it meets rigorous standards in research, leadership, training programs, and community outreach. The center will receive $2.1 million a year to help attract world-class researchers and clinical investigators, train the next generation of cancer researchers, and increase its competitiveness for research grants.
• A tornado severely damaged a Pfizer drug warehouse and manufacturing plant in Rocky Mount, NC. The company said that about 25% of the sterile injectable drugs it sends to U.S. hospitals were made at that facility. Reports noted that the Rocky Mount site produced intravenous anesthetics, pain medications, and infection-fighting antibiotics; specific drugs and the conditions they treat haven't been named.

• Researchers reported that, based on the phase I/II BRUIN study in adults with chronic lymphocytic leukemia and small lymphocytic lymphoma, those who develop resistance to covalent BTK inhibitors respond to the noncovalent BTK inhibitor pirtobrutinib (Jaypirca; Loxo@Lilly; N Engl J Med 2023;389:33–44). Among 247 patients who had previously received a covalent BTK inhibitor, 73.3% responded to pirtobrutinib; progression-free survival was 19.6 months. Notably, the low incidences of atrial fibrillation, major hemorrhage, and hypertension, adverse events associated with covalent BTK inhibitors, "are encouraging" and signal "the high degree of BTK selectivity with pirtobrutinib and a relative absence of off-target inhibition."
• The FDA removed the partial clinical hold on Curis's phase I/II study of emavusertib, a small-molecule inhibitor of IRAK4, FLT3, and CLK, in combination with azacitidine and venetoclax (Venclexta; AbbVie/Genentech) for the treatment of relapsed/refractory acute myelogenous leukemia or myelodysplastic syndromes. The hold was initiated in April 2022 and was lifted on the monotherapy dose-finding portion of the trial in August 2022; enrollment can now continue in the combination arm.
• Contrary to long-held beliefs, cells preparing to divide can reverse the process and return to a resting state, NCI researchers reported (Nature 2023 Jul 5 [Epub ahead of print]). Researchers captured videos of thousands of cells of different types undergoing mitosis and noticed that when growth-promoting signals were stopped, about 15% of cells halted progress through the cell cycle—namely those cells that were in the early stages of dividing. The work could lead to more effective methods of interrupting the division of cancer cells and a better understanding of the cell-cycle regulators CDK4 and CDK6.

• Researchers reported that, based on data from the FDA and European Medicines Agency, less than half of 124 approved first indications for drugs have a "high therapeutic value" (BMJ 2023;382:e074166). The study examined all new drugs, about half of which were for the treatment of cancer, approved for multiple indications by both agencies between January 2011 and December 2020. The likelihood that supplemental indications were "rated as having high added therapeutic value" was even "substantially lower than for the drugs' initial indications. When indications do not offer added therapeutic benefit over other available treatments, that information should be clearly communicated to patients and reflected in the price of the drugs," the researchers wrote.
• According to a study by the U.S. Geological Survey, water from about 45% of public and private faucets contains "forever chemicals," known as PFAS, which have been associated with kidney and testicular cancers, as well as other health problems. The largest concentrations of PFAS were found in cities and areas near companies that use the compounds, which are found in nonstick cookware, packaging, and waterproof clothing. PFAS remain in the body for years and do not break down in the environment.

• At the European Society for Medical Oncology World Congress on Gastrointestinal Cancer in Barcelona, Spain, researchers reported that a two-drug regimen demonstrated a clinically meaningful overall survival (OS) benefit in patients with inoperable hepatocellular carcinoma who hadn't received a systemic therapy and weren't eligible for localized treatment. According to updated results from the phase III HIMALAYA trial, the combination of AstraZeneca's PD-1 inhibitor durvalumab (Imfinzi) and CTLA4 inhibitor tremelimumab (Imjudo)—known as STRIDE—reduced the risk of death by 22% compared with standard sorafenib (Nexavar; Bayer). After 4 years, the OS rate was 25.2% with STRIDE and 15.1% with sorafenib, but the rate of serious treatment-related adverse events was also higher—17.5% vs. 9.6%, respectively.
• The Biden administration awarded $50 million to launch the Persistent Poverty Initiative, which will be coordinated by the NCI and NIH, to improve how patients fare with cancer in low-income areas by increasing research; fostering cancer prevention efforts, such as tobacco cessation and access to healthy food; and promoting the implementation of community-based programs to improve living conditions and help boost the economy. Persistent poverty areas are defined as locations where, for the past 30 years, 20% or more of the population has lived below the federal poverty line. People who live in these areas have a higher incidence of cancer, experience longer delays in cancer diagnosis and treatment, and are more likely to die from their cancer than people in wealthier communities.
• Eli Lilly will acquire the German biotech Emergence Therapeutics, which develops antibody–drug conjugates; terms of the deal were not announced. Emergence's lead drug candidate, ETx-22, takes aim at Nectin-4, which is overexpressed in most bladder cancers.

• Bayer announced that the FDA approved iopromide (Ultravist), an iodine-based contrast agent, for contrast-enhanced mammography. As an adjunct to mammography and/or ultrasound, the product can help clinicians identify breast lesions—especially in women at high risk for breast cancer and women with dense breasts in which lesions can be challenging to spot.
• GSK settled its first lawsuit over Zantac (ranitidine), brought by a California man who alleged that he developed bladder cancer from the heartburn drug; terms of the settlement were not released. Reports emerged in 2019 that ranitidine, the active ingredient in Zantac, can degrade over time and form NDMA, a possible carcinogen; the following year, the FDA ordered that Zantac and other ranitidine-based drugs be removed from the market. Thousands of lawsuits related to Zantac, which has been sold by multiple pharmaceutical companies, are pending.
• Reuters reported that aspartame will be deemed "possibly carcinogenic to humans" by the International Agency for Research on Cancer (IARC), which is part of the World Health Organization (WHO), next month. The artificial sweetener is commonly found in products such as gum, sodas, and other beverages, but the group does not say how much aspartame can be safely consumed. A separate WHO committee is set to report on that in mid-July, when the IARC makes its formal announcement.

• The U.S. Department of Health and Human Services issued an alert to health care providers about a ransomware attack on an unnamed cancer center that "significantly reduced patient treatment capability, rendered digital services unavailable, and also threatened exposure of patient personal health information and personal identifiable information" (https://www.hhs.gov/sites/default/files/healthcare-public-health-sector-cybersecurity-notification.pdf). The alert noted that "healthcare is particularly vulnerable to cyberattacks, owing to their high propensity to pay a ransom, the value of patient records, and often inadequate security." The group of hackers, known as the TimisoaraHackerTeam, encrypts files and demands a ransom to unlock affected servers.
• A new drug combination could become a standard regimen for preventing graft-versus-host disease (GVHD) following an allogeneic hematopoietic stem cell transplant, researchers reported (N Engl J Med 2023;388:2338–48). In a phase III trial, 52.7% of 214 patients who received cyclophosphamide, tacrolimus, and mycophenolate mofetil were free of GVHD and cancer relapse after 1 year vs. 34.9% of 217 patients who received the current standard of tacrolimus and methotrexate. The three-drug regimen caused fewer side effects as well.
• Pfizer announced that the FDA approved talazoparib (Talzenna) for certain prostate cancers—namely those with homologous recombination repair (HRR) gene–mutated metastatic castration-resistant disease—when given in combination with enzalutamide (Xtandi; Astellas/Pfizer). The decision was based on findings of the phase III TALAPRO-2 trial, which demonstrated a 55% reduction in the risk of disease progression or death in patients with this cancer and prospectively identified HRR mutations in genes such as ATM, BRCA1, and BRCA2, among others.

• Following a nationwide inspection blitz, the FDA sent warning letters to 189 retailers caught selling unauthorized tobacco products, namely the popular Elf Bar and Esco Bars. Both items are disposable electronic cigarettes (e-cigarettes) that come in flavors that appeal to youth, such as bubblegum and cotton candy, and that pose health risks to users. A recent study found that thousands of reports of e-cigarette exposure were made to U.S. poison control centers in the past year, mostly involving children under 5 years old.
• Among 58 clinical trials conducted within the Alliance for Clinical Trials in Oncology, 1,060 of 11,993 patients (9%) withdrew their consent from their trial within 2 years (JAMA Oncol 2023 Jun 22 [Epub ahead of print]). Patients most likely to withdraw were of Hispanic ethnicity, were participating in a placebo-controlled trial, or were age 75 or older; patients receiving radiation were more likely to continue participating. Although patient explanations for backing out of a study weren't available, researchers said that investigators need to take the withdrawal rate into account when designing trials.

• Oncologists pressed U.S. lawmakers to find ways to ease chemotherapy shortages during a hearing of the House Energy & Commerce Subcommittee on Health, The Hill reported. Earlier this month, the National Comprehensive Cancer Network drew attention to the problem when it published results of a survey of leading academic medical centers that found 93% and 70% were experiencing shortages of carboplatin and cisplatin, respectively (see http://www.nccn.org). In the survey, conducted from May 22–31, the centers reported they had still been able to treat all their patients who needed cisplatin, but only 64% of them could keep all patients requiring carboplatin on their prescribed regimen.
• Cancer incidence in the United States remained relatively stable from 2011–2019 at roughly 456 cases per 100,000 people per year. However, in 2020, the first year of the COVID-19 pandemic, cancer incidence dropped by 11% overall—to 403 cases per 100,000 people—according to data released by the Centers for Disease Control and Prevention (CDC) and the NCI (U.S. Cancer Statistics Data Briefs, no. 35, June 2023). The CDC noted that the "downward trends may be due largely to…missed diagnoses related to disruptions in health services and cancer reporting caused by the COVID-19 pandemic" and are highly unlikely to be a true decline.
• Mersana Therapeutics announced that the FDA issued a partial clinical hold on two trials assessing upifitamab rilsodotin (UpRi), an antibody–drug conjugate (ADC) targeting NaPi2b, as a treatment for platinum-sensitive ovarian cancer. The company reported that five of approximately 560 patients who have received UpRi have died from serious bleeding; current trial participants can continue to receive the medication, but additional patients will not be enrolled until the company and the FDA fully assess safety issues. Top-line efficacy and safety data from a third trial of UpRi should be available in August.

• Similarly, 2seventy bio announced that its partner, Seattle Children's Hospital, has paused the phase I PLAT-08 trial of SC-DARIC33 following the death of a patient. The chimeric antigen receptor T-cell therapy is being studied in children and young adults with relapsed/refractory CD33-positive acute myeloid leukemia. The company said it is investigating the cause of the death.
• Seagen announced that brentuximab vedotin (Adcetris) plus an immunotherapy combination yielded a 93% complete response rate in 150 patients with early-stage classical Hodgkin lymphoma in a phase II trial evaluating the CD30-directed ADC; the overall response rate was 98%. Standard treatment regimens in the United States include a combination of doxorubicin, bleomycin, vinblastine, and dacarbazine or that combination with brentuximab but without vinblastine. The combination under investigation includes brentuximab, the PD-1 inhibitor nivolumab (Opdivo; Bristol Myers Squibb), doxorubicin, and dacarbazine. The company suggested that replacing bleomycin and vinblastine likely led to reduced incidence and severity of peripheral sensory neuropathy—and no instances of febrile neutropenia.

• The FDA will allow the temporary importation of cisplatin and carboplatin from a Chinese company to help alleviate shortages of the drugs in the United States, according to CNN. "We very carefully assess product quality and require companies to take certain measures to ensure the products are safe for patients," said FDA Commissioner Robert Califf, MD. "The public should rest assured that we will continue all efforts within our authority to help the industry that manufactures and distributes these drugs meet all patient needs for the oncology drugs impacted by shortages."
• Merck filed suit against the U.S. government over a provision in the Inflation Reduction Act (IRA) that would allow Medicare to negotiate prices of some drugs with drugmakers, calling it unconstitutional. The policy, which will go into effect in 2026, could significantly lower the company's profits if prices are reduced on some of its biggest sellers, such as the PD-1 inhibitor pembrolizumab (Keytruda). Merck argues that the law could stifle innovation: "By changing the incentives and returns for some therapies and technologies over others, the IRA is changing the course of R&D, which in time will leave many patients without treatment options."
• The FDA issued a draft guidance "aimed at modernizing the design and conduct of clinical trials, making them more agile without compromising data integrity or participant protections." The draft guidance is adopted from the Good Clinical Practice guidelines of the International Council for Harmonisation (ICH). According to the FDA document, "ICH guidelines have substantially reduced duplicative clinical studies, prevented unnecessary animal studies, standardized safety reporting and marketing application submissions, and contributed to many other improvements." The document is available at www.fda.gov.
• At the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL, held June 2–6, researchers announced that there's no benefit to adding the PD-L1 inhibitor atezolizumab (Tecentriq; Roche) to the multi–tyrosine kinase inhibitor cabozantinib (Cabometyx; Exelixis) as a second-line therapy for patients with renal cell carcinoma after a first-line immune checkpoint inhibitor (ICI) stops working. "Rechallenging" patients with this ICI did not improve progression-free survival, overall response rates, or overall survival, but it did increase side effects (Lancet 2023 Jun 5 [Epub ahead of print]). "This is a negative study," said Toni Choueiri, MD, of Dana-Farber Cancer Institute in Boston, MA, "but this is an important question."
• Also at the ASCO meeting, researchers reported that the chimeric antigen receptor T-cell therapy ciltacabtagene autoleucel (cilta-cel; Carvykti; Janssen) slows or stops progression of multiple myeloma compared with standard-of-care treatment in patients whose disease no longer responds to lenalidomide (N Engl J Med 2023 Jun 5 [Epub ahead of print]). In the global, phase III CARTITUDE-4 clinical trial, which included 419 patients, cilta-cel reduced the risk of disease progression by 74% compared with standard-of-care treatment after a median follow-up of 16 months. The objective response rates were 84.6% and 67.3%, respectively.
• At a STAT event timed to fall during the ASCO meeting, Director of the FDA's Oncology Center of Excellence Richard Pazdur, MD, addressed comments made by Califf earlier this year about whether a committee evaluating drugs should vote on their approval even though that decision falls to the FDA. Unlike Califf, Pazdur appreciates advisory committee votes. "We have to make a binary decision at the FDA whether to or not to approve. If we are going in one direction and we hear a unanimous vote against, we have to pause. You have to step back and say, ‘Were we wrong on this?'" he explained.

• According to Dennis Slamon, MD, PhD, of the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, adding ribociclib (Kisqali; Novartis) to endocrine therapy led to a significant improvement in invasive disease-free survival (iDFS) compared with endocrine therapy alone. In the phase III NATALEE trial, the 3-year iDFS rates were 90.4% and 87.1%, respectively, in patients with hormone receptor–positive, HER2-negative breast cancer. A CDK4/6 inhibitor, ribociclib also reduced the risk of disease recurrence by 25%, Slamon reported at the ASCO meeting.
• Combining the PARP inhibitor talazoparib with enzalutamide yields clinically meaningful and statistically significant improvement in radiographic progression-free survival (rPFS) compared with enzalutamide alone as an initial treatment for men with metastatic castration-resistant prostate cancer, according to findings of the TALAPRO-2 study presented at the ASCO meeting (Lancet 2023 Jun 4 [Epub ahead of print]). After a median follow-up of nearly 25 months, rPFS was not reached in the talazoparib group, which included 402 patients, compared with 21.9 months in the 403 patients who received enzalutamide alone.
• Shubham Pant, MD, MBBS, of The University of Texas MD Anderson Cancer Center in Houston, reported at the ASCO meeting that patients with HER2-amplified biliary tract cancer experience clinically meaningful improvement with zanidatamab, a bispecific antibody; the findings were simultaneously reported in a medical journal (Lancet Oncol 2023 Jun 2 [Epub ahead of print]). In 87 patients with the disease enrolled in the phase IIb HERIZON-BTC-01 study, 33 responded to the drug after a median follow-up of 12.4 months. Although 18% of patients experienced grade 3 treatment-related adverse events, such as diarrhea and decreased ejection fraction, side effects were generally manageable.
• Also at the ASCO meeting, DIPLOMA trial researchers presented data showing that minimally invasive distal pancreatectomy with splenectomy is a safe and effective alternative to traditional open surgery for patients with early-stage operable pancreatic cancer. As part of the study, 231 patients underwent one of the two procedures, and, overall, patients who had the minimally invasive procedure, which requires multiple small incisions, fared just as well as those who had open surgery, which involves one large incision. The minimally invasive surgery had a lower risk of serious complications compared with open surgery.

• The FDA approved an olaparib (Lynparza; AstraZeneca) regimen—a combination of the PARP inhibitor, abiraterone (Zytiga; Janssen), and prednisone or prednisolone—to treat men with BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC). In the PROpel trial, 796 patients with mCRPC received abiraterone and prednisone/prednisolone with or without olaparib. In the subgroup of 85 patients with a BRCA mutation, those who did not receive olaparib had a median radiologic progression-free survival (PFS) of 8 months, but among those who did, median PFS was not reached.
• Blueprint Medicines announced that the FDA approved avapritinib (Ayvakit) to treat adults with indolent systemic mastocytosis (SM). The drug—designed to inhibit KIT^D816V, the primary underlying driver of the disease—was found to significantly improve disease symptoms and mast cell burden in the PIONEER trial. Avapritinib was already approved for advanced SM, SM with an associated hematologic neoplasm and mast cell leukemia, and inoperable or metastatic gastrointestinal stroma tumors harboring a PDGFRA exon 18 mutation, including PDGFRA^D842V mutations.
• Immutep announced encouraging clinical data for eftilagimod in conjunction with standard-of-care anti–PD-1 therapy and chemotherapy as an initial treatment for metastatic non–small cell lung cancer (NSCLC). Thus far, the combination has yielded a 91% disease control rate and an overall response rate (ORR) of 67% regardless of PD-L1 expression. Notably, the ORR was 65% in patients with a PD-L1 proportion score of less than 50%—patients who are generally less responsive to anti–PD-1 therapies than patients with a higher score. Eftilagimod is a soluble LAG-3 protein and MHC class II agonist that leads to the activation and proliferation of CD8⁺ cytotoxic T cells, CD4⁺ helper T cells, dendritic cells, natural killer cells, and monocytes.

• Mirati Therapeutics announced that the SAPPHIRE study did not meet its primary endpoint of overall survival in its final analysis. The phase III study was evaluating sitravatinib in combination with nivolumab (Opdivo; Bristol Myers Squibb) vs. docetaxel in patients with NSCLC whose disease progressed despite treatment with chemotherapy and an immune checkpoint inhibitor. Trial participants who are benefiting from the drug can remain on treatment.
• Researchers reported that the phase III KEYNOTE-826 trial shows that PFS and overall survival improve for patients with certain cervical cancers when they receive a combination of the PD-1 inhibitor pembrolizumab (Keytruda; Merck) and chemotherapy—with or without bevacizumab—compared with chemotherapy with or without bevacizumab. Improvements were seen regardless of PD-L1 expression. The final results of the study will be presented at the 2023 American Society of Clinical Oncology Annual Meeting, which starts on June 2 in Chicago, IL.

• The FDA issued two draft guidances to support the approval of therapies for children—drugs, biological products, and vaccines—based on the Pediatric Research Equity Act (PREA) and the Best Pharmaceuticals for Children Act (BPCA), available at https://www.fda.gov/media/168201/download and https://www.fda.gov/media/168202/download. The documents "provide the agency's current thinking about how industry can comply with PREA and BPCA, thus helping to increase the availability and timeliness of safe and effective medicines and vaccines for children" in the United States, said Lynne Yao, MD, director of the FDA's Division of Pediatrics and Maternal Health. Comments on the draft documents can be made through July 17 at https://www.regulations.gov.
• Researchers reported that the economic burden of health disparities is unacceptably high in the United States (JAMA 2023;329:1682–92). The groundbreaking study found that racial and ethnic health disparities cost the U.S. economy an estimated $451 billion, a 41% increase over 2014. The study also found that the burden of education-related health disparities in 2018 for people without a college degree was roughly $978 billion—about twice the annual growth rate of the U.S. economy in 2018.
• A jury awarded $19.35 million to Natera in a patent dispute with ArcherDX/Invitae for lost profits and a past royalty of 10%. The jury in the U.S. District Court for the District of Delaware unanimously agreed that ArcherDX/Invitae infringed on three of Natera's patents. Natera is a leader in cell-free DNA testing.

• Findings from a new study suggest that pancreatic cancer cells can switch from glucose to uridine as a fuel source when glucose is limited, allowing them to continue growing (Nature 2023 May 17 [Epub ahead of print]). Researchers found that uridine can be broken down by uridine phosphorylase-1 (UPP1), which produces ribose to fuel cancer cells in the absence of glucose. In mouse studies, knocking out UPP1 blocked the use of uridine by pancreatic cancer cells and helped stop tumor growth.
• The FDA issued marketing denial orders to 10 companies that collectively make and market approximately 6,500 flavored electronic cigarettes (e-cigarette) and the liquids used in e-cigarettes, known as e-liquids. The agency considered whether the products showed an added benefit to adult smokers compared with tobacco-flavored e-liquid and e-cigarette products—and whether that benefit could outweigh the risk of flavored e-liquid and e-cigarette products to youth. The agency determined that information submitted by the companies was "not sufficient to demonstrate such a benefit."

• Based on recent research, a panel of experts in screening and prevention plans to drop the age for starting mammography to 40 for women at average risk of breast cancer. The U.S. Preventive Services Task Force (USPSTF) currently recommends biennial screening for women beginning at age 50, but notes that women may opt to start in their 40s. In crafting the draft recommendation, the USPSTF considered disparities in age of diagnosis and survival—Black women tend to develop aggressive cancers at a younger age and are 40% more likely to die of breast cancer than white women—even so, starting screening at age 40 proves moderately beneficial for all women. Comments on the draft recommendation can be made until June 5 at www.uspreventiveservicestaskforce.org.
• Researchers reported that being overweight or obese in early and middle adulthood is associated with a greater risk of gastrointestinal (GI) cancers, including both colorectal and noncolorectal GI cancers (JAMA Netw Open 2023;6:e2310002). Their conclusion was based on an analysis of data from 135,161 participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. They said that additional studies should explore the role of excess weight in carcinogenesis.
• Another study probed that question, noting that it's plausible for changes in peripheral natural killer (NK) cell activity, which are common in people with obesity, to increase cancer risk. In 20 people with obesity, researchers found that therapy with the glucagon-like peptide-1 analogue semaglutide can restore NK cell function (Obesity 2023 May 9 [Epub]). Researchers said that the effect of semaglutide—found in drugs such as Ozempic (Novo Nordisk) and others used to treat obesity—appears to be independent of weight loss.

• The FDA decided not to approve ImmunityBio's N-803 (Anktiva) in combination with bacillus Calmette-Guérin (BCG) to treat patients with BCG-unresponsive non–muscle invasive bladder cancer, according to a filing with the U.S. Securities and Exchange Commission. The FDA cited deficiencies with the company's third-party contract manufacturer; no new preclinical or phase III trials were requested by the agency. Designed to boost NK and T cells, N-803 is an IL15 superagonist complex that consists of an IL15 mutant bound to an IL15 receptor α/IgG1 Fc fusion protein.
• A new report indicates that cervical cancer screening doubles when under-screened women receive an at-home test kit via mail and assistance in booking screening appointments at a clinic compared with booking assistance alone (Lancet Public Health 2023 May 11 [Epub ahead of print]). The My Body, My Test-3 Study enrolled 665 women in North Carolina, ages 25 to 64, with low incomes who hadn't had a Pap test in 4 years or a human papillomavirus (HPV) test in 6 years. Screening uptake was 72% among women who received at home HPV tests compared with 37% in the other group of women.

• AstraZeneca announced that the FDA's Oncologic Drugs Advisory Committee (ODAC) voted 11 to 1 to recommend approval of an olaparib (Lynparza) regimen to treat BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC), based on the results of the phase III PROpel trial. Although the trial of the PARP inhibitor combined with abiraterone and prednisone or prednisolone in men regardless of mutation status, the committee found the bulk of the benefit was attributable to patients with BRCA mutations and not the entire study population. The FDA is not required to follow the ODAC's recommendation and could approve the drug combination as a first-line treatment for all patients with mCRPC or to the BRCA-mutated population only.
• The FDA issued draft guidance regarding the implementation of decentralized clinical trials (DCT), in which some or all of a trial's activities take place remotely—in participants' homes or in local health care facilities, for example, to minimize travel to clinical trial sites—using telehealth and digital health technologies. DCTs, the agency says, could attract more study participants, increase trial diversity, and make trials more efficient. Comments on the draft, available at https://www.fda.gov/media/167696/download, can be made until August 1.
• In patients with Bacillus Calmette-Guerin–unresponsive high-risk non–muscle invasive bladder cancer, Janssen's investigational TAR-200 monotherapy, as well as its investigational PD-1 inhibitor cetrelimab, demonstrated strong responses in patients who cannot have or decline to have a radical cystectomy, according to data presented at the American Urological Association Annual Meeting in Chicago, IL. Among 23 patients who received TAR-200, a drug delivery system that provides sustained release of gemcitabine into the bladder, 72.7% experienced complete responses (CR); 38.1% of patients who received cetrelimab had a CR. However, seven and two patients, respectively, experienced adverse event of grade 3 or higher. Data from patients who received both drugs were not released.

• Amgen filed a lawsuit against Sandoz and Novartis alleging patent infringement on Prolia and Xgeva, used to treat osteoporosis and to prevent spinal fractures in patients whose cancer has metastasized to bone, respectively; the active ingredient in both agents is denosumab, an IgG2 mAb with affinity and specificity for RANKL. Sandoz/Novartis applied to the FDA for approval to make and market biosimilar versions of Amgen's drugs even though Amgen holds patents on the products that haven't expired. The suit was filed in U.S. District Court for the District of New Jersey.
• Researchers reported that uterine leiomyomas and endometriosis increase the risk of ovarian cancer in both Black and white women. Hysterectomy following a diagnosis of uterine leiomyomas reduced the risk in both races; however, hysterectomy in women with endometriosis modified ovarian cancer risk only in white women (Obstet Gynecol 2023 May 5 [Epub ahead of print]). Researchers aren't sure why the discrepancy exists, but studies of access to care and treatment could point to more effective prevention methods and medical interventions, the authors say.

• Quest Diagnostics announced it will acquire Haystack Oncology for up to $450 million. Haystack developed circulating tumor DNA–based technology to detect minimal residual disease (MRD) following surgery, identifying the patients who need adjuvant chemotherapy—reducing the need to prescribe chemotherapy to every patient without compromising recurrence-free survival. Quest says that it will adapt Haystack's MRD test for use in colorectal, breast, and lung cancers, with new clinical lab services becoming available next year.
• Researchers developed a test to determine which patients with clonal hematopoiesis (CH) are most likely to develop myeloid malignancies (NEJM Evid 2023;2(5):10.1056/evidoa2200310). Using exome sequencing data to find mutations associated with CH, as well as demographic and laboratory information to identify measures highly predictive of blood cancer risk, the researchers created a tool to calculate a CH risk score to stratify patients into three risk groups (see http://www.chrsapp.com). The chance of developing a blood cancer in the next 10 years is less than 1% in the low-risk group, but it jumps to more than 50% in the high-risk group, allowing oncologists to determine the best care plan for each patient.
• Roche announced that the IMpassion030 study has been discontinued. A data monitoring committee analysis determined that the trial, which was evaluating a combination of the PD-L1 inhibitor atezolizumab (Tecentriq) plus chemotherapy versus chemotherapy alone as an adjuvant treatment, was unlikely to meet its primary endpoint—invasive disease-free survival—in patients with triple-negative breast cancer (TNBC). Atezolizumab had once been granted accelerated approval for first-line treatment of TNBC, but the approval was rescinded after a confirmatory trial failed to show a benefit.

• Janssen announced that the European Commission granted marketing authorization to niraparib plus abiraterone acetate (Akeega), a dual-action tablet given with prednisone or prednisolone to treat patients with metastatic castration-resistant prostate cancer and BRCA1/2 mutations. The approval is based on results of the phase III MAGNITUDE study, which found that the combination reduced the risk of radiographic progression-free survival by 47% compared with placebo plus abiraterone acetate and prednisone or prednisolone.
• Foghorn Therapeutics paused enrollment in a study of FHD-609 in synovial sarcoma and SMARCB1-deleted tumors after a patient receiving the second highest dose of the drug experienced prolonged contraction of the heart between heartbeats; it was deemed a grade 4 adverse event. Patients in the early-phase trial who are benefiting from the drug can continue to receive it. FHD-609 is designed to correct abnormal expression of SMARCB1.

• "We should focus not only on barriers but solutions," said Folakemi Odedina, PhD, of the Mayo Clinic in Jacksonville, Florida, while discussing disparities in oncology clinical trials at the American Association for Cancer Research (AACR) Annual Meeting 2023. Obstacles to trial participation exist at the personal, provider, health system, and protocol levels for a significant portion of cancer-focused studies, she said, adding that efforts to decentralize clinical trials could address these disparities and broaden diversity of participants.
• Genentech's atezolizumab (Tecentriq) combined with bevacizumab increased recurrence-free survival (RFS) of patients with hepatocellular carcinoma (HCC) following surgery or ablation, according to the results from the phase III IMbrave050 study presented at the AACR meeting. Patients who received the combination reduced their risk of disease recurrence or death by 28% compared with those in the active surveillance control arm. Pierce Chow, PhD, FRCS(E), of National Cancer Centre Singapore and Singapore General Hospital, noted that patients received the drugs several months longer than in the IMbrave150 trial of the same drug combination in patients with inoperable HCC, but the incidence of serious adverse events was comparable.
• Allogene Therapeutics' ALLO-316 showed promising antitumor activity against advanced or metastatic clear-cell renal cell carcinoma and a tolerable safety profile based on early phase I data presented at the AACR meeting by Samer Srour, MB ChB, MS, of The University of Texas MD Anderson Cancer Center in Houston. After a median follow-up of 7.8 months, the allogeneic anti-CD70 chimeric antigen receptor T-cell therapy demonstrated an overall response rate (ORR) of 17% and a disease control rate (DCR) of 89% in 18 evaluable patients. However, in the 10 patients with CD70-positive disease, the ORR was 30%, the DCR was 100%, and median progression-free survival (PFS) was 5 months.
• Merck's PD-1 inhibitor pembrolizumab (Keytruda), when added to gemcitabine and cisplatin, improved overall survival (OS) in patients with biliary tract cancer, researchers reported at the AACR meeting; findings were concurrently published (Lancet 2023 Apr 16 [Epub ahead of print]). Among 1,069 patients with untreated or inoperable disease, those assigned to receive the pembrolizumab combination experienced a median OS of 12.7 months compared with 10.9 months among patients who received chemotherapy alone. The phase III KEYNOTE-966 study also found that patients treated with pembrolizumab had a 17% lower risk of death after a median follow-up of 25.6 months.
• "Cessation is key," said Brian King, PhD, MPH, director of the FDA Center for Tobacco Products, at the AACR meeting. He told attendees that the FDA is working to establish a maximum nicotine level for cigarettes and other combustible tobacco products that could help reduce their addictiveness. He also stressed that promoting cessation at the individual, health system, and population levels is essential to reducing tobacco-related disease and death.
• Cancer diagnoses during pregnancy have increased in recent years, reported Ann Partridge, MD, MPH, of Dana-Farber Cancer Institute in Boston, MA, at the AACR meeting. The rising incidence of early-onset cancers and the increasing average age of first-time mothers were found, in part, to be contributing factors. Findings point to the critical need to further evaluate the safety and efficacy of anticancer agents for the treatment of patients who are pregnant.
• Although many pancreatic tumors are considered immunologically "cold," research presented at the AACR meeting indicated that mRNA vaccines can spark de novo immunity in pancreatic ductal adenocarcinoma. Patients who did not respond to customized vaccines from Genentech and BioNTech experienced a median RFS of 13.4 months, whereas RFS in responders has not been reached, reported Vinod Balachandran, MD, of Memorial Sloan Kettering Cancer Center in New York, NY. Phase II trials are slated to start within the year.

• Also at the AACR meeting, Owen Wallace, PhD, of Monte Rosa Therapeutics, discussed the preclinical activity of MRT-2359, an orally bioavailable GSPT1 molecular glue degrader. The drug blocks protein translation, which is thought to be a vulnerability in MYC-driven tumors. Testing of MRT-2359 in lung cancer patient-derived xenografts revealed preferential dose-dependent antitumor activity in N- or L-MYC–high tumors. Phase I dose-escalation studies are underway in multiple solid tumor types, including MYC-driven lung cancers and diffuse large B-cell lymphoma (DLBCL).
• "Treat the biology, not the diagnosis," said E. Shelley Hwang, MD, MPH, of Duke Cancer Institute in Durham, NC, during her AACR meeting presentation on profiling ductal carcinoma in situ (DCIS). She said that risk stratification tools to evaluate DCIS that is contained versus DCIS that has progressed to invasive cancer can help clinicians decide when, along the breast cancer continuum, to intervene.

In other news, April 14–21:

• Multiple media outlets reported that President Joe Biden will nominate NCI Director Monica Bertagnolli, MD, to head the NIH. The U.S. Senate would need to vote on her confirmation. Biden named Bertagnolli to the NCI post last October.
• The FDA approved polatuzumab vedotin (Polivy; Genentech) for untreated DLBCL or high-grade B-cell lymphoma. The CD79b-directed antibody–drug conjugate would be given with the drug cocktail that includes rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP)—in other words, polatuzumab vedotin would replace vincristine in what's known as the R-CHOP regimen. In the POLARIX trial, patients who received polatuzumab vedotin plus R-CHP had significantly longer PFS and modified event-free survival compared with patients who received R-CHOP. However, no significant difference was observed in the complete response rate or OS.

• Electronic cigarette maker Juul will pay $462 million to six states and the District of Columbia to settle claims that the company misled consumers about the health risks associated with its products and that it contributed to a dramatic rise in vaping among youth by advertising the devices directly to teens. In addition to the fine, the settlement forces retailers to secure Juul products behind the counter and ensure that buyers are of legal age; also, Juul must stop including people younger than 35 in marketing materials.
• The U.S. Environmental Protection Agency (EPA) proposed health protections to reduce exposure to ethylene oxide, a carcinogenic gas mainly used to sterilize medical devices. If finalized, the EPA's proposals are estimated to cut ethylene oxide emissions from commercial sterilization facilities by 80% per year, reducing worker and community exposure to the toxic chemical. The proposal advances President Joe Biden's commitment to cut the cancer death rate in half within 25 years.

• Amended this week, the Cancer Prevention Act, a bill under consideration in California, would require college students to be fully immunized against human papillomavirus (HPV) before enrolling at an institution that's part of the California State University, the University of California, or the California Community Colleges. HPV can cause cervical, anal, oral, and penile cancers. The move wouldn't be unprecedented: The state already mandates, with some exceptions, that first-time enrollees at these institutions who are 18 or younger provide evidence of vaccination against hepatitis B.

• The U.S. Federal Trade Commission (FTC) ordered Illumina to divest itself of GRAIL, which makes multicancer early detection tests. The FTC concluded that Illumina's $7.1 billion acquisition of GRAIL in 2020 "would stifle competition and innovation in the U.S. market for life-saving cancer tests" and drive up prices. San Diego, CA–based Illumina makes next-generation sequencing tools that analyze blood samples taken for liquid biopsies.
• The NCI released its National Cancer Plan, which outlines the goals that must be met to prevent cancer, reduce cancer mortality, and maximize quality of life and offers strategies to meet those goals (http://nationalcancerplan.cancer.gov). It also issues a call to action, asking "everyone in our society, every organization and individual, do their part to end suffering from cancer." For more about the National Cancer Plan, see Cancer Discovery's article "National Plan Unveiled to Combat Cancer."
• The Society for Immunotherapy of Cancer (SITC) issued consensus definitions for immune-related adverse events (irAE) associated with immune checkpoint inhibitors (J Immunother Cancer 2023;11:e006398). irAEs can vary widely in their clinical presentation, response to treatment, and patterns of development, making their management difficult for clinicians due to the lack of common and consistently used terminology. SITC says that the adopting a standard vocabulary for irAEs will aid in the implementation of clinical practice guidelines and aid in the conduct of irAE clinical trials.

• The FDA granted accelerated approval to enfortumab vedotin (Padcev; Astellas) with pembrolizumab (Keytruda; Merck) to treat locally advanced or metastatic urothelial carcinoma. In the EV-103/KEYNOTE-869 trial, the overall response rate in 121 patients was 68%, with a complete response rate of 12%. The most common adverse reactions were laboratory abnormalities, such as decreased hemoglobin; rash; and fatigue.
• Janssen and Pharmacyclics announced that ibrutinib (Imbruvica) will be voluntarily withdrawn in the United States to treat certain lymphomas—namely mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL), which are subtypes of non-Hodgkin lymphoma. Ibrutinib had received accelerated approval for the indications based on phase II trials, but continued approval was contingent upon demonstrating its clinical benefit in a phase III trial. Although a trial in MCL showed a significant improvement in progression-free survival (PFS) with the Bruton tyrosine kinase inhibitor, it did not prolong overall survival; a phase III trial in MZL didn't meet its primary endpoint of improved PFS. The decision does not apply to other ibrutinib indications or outside of the United States.

• A federal judge overturned part of the Affordable Care Act that calls for free cancer screening and other preventive care services. Although the ruling takes effect immediately, insurers aren't likely to reinstate copayments for mammograms, pap tests, colonoscopies, and other types of screening any time soon, The New York Times reported. Experts said that insurance contracts are already in place for this year and that companies would want time to alert consumers about any changes in coverage.
• Contrary to studies indicating that neutrophils around a tumor can help it survive, a T cell–based immunotherapy destroyed melanomas in mice—even though many of the tumor cells no longer expressed the targeted antigen, Trp1—by activating these white blood cells, researchers reported (Cell 2023;186:1432–47). They found that the antitumor activity of the T cells against the Trp1-expressing melanoma summoned neutrophils to the tumor, which then killed the non–Trp1-expressing cells by, at least in part, secreting nitric oxide. The researchers say that the discovery could prompt the development of immunotherapies that harness this immune response.
• Underscoring concern around the world about drug prices, the Netherlands health ministry announced that it will not cover sacituzumab govitecan (Trodelvy; Gilead) to treat patients with triple-negative breast cancer, saying that the Trop-2–directed antibody–drug conjugate is not cost-effective. The Dutch government had been seeking to lower the average $75,000 cost per patient—or nearly $10.5 million for about 139 patients per year—but wasn't able to secure that concession. The drug would improve patient survival by about 5.4 months.

• Examining exome sequencing data from 510 patients in Poland with a family history of breast cancer, researchers uncovered a rare gene mutation in ATRIP in two women (Am J Hum Genet 2023 Mar 27 [Epub ahead of print]). They subsequently found the variant in a much larger national cohort of patients and control subjects; in sequencing data from UK Biobank study participants, ATRIP loss-of-function variants were found in 13 of 15,643 people with breast cancer and 40 of 157,943 controls. Based on their findings, the researchers reported that ATRIP is a breast cancer susceptibility gene candidate, "linking DNA replication stress to breast cancer."
• The FDA's partial hold on Blueprint Medicines' BLU-222 was lifted, and clinical trial sites have restarted patient enrollment in the phase I/II VELA study, which is assessing the CDK2 inhibitor in patients with advanced solid tumors. The hold was initiated in February following reports of light sensitivity and blurred vision in some patients.

• Incyte announced that the FDA greenlighted retifanlimab (Zynyz) to treat adults with metastatic or recurrent locally advanced Merkel cell carcinoma. The decision was based on data from the single-arm POD1UM-201 trial, in which 65 chemotherapy-naive patients received retifanlimab as a monotherapy. The overall response rate was 52%, with a complete response in 12 patients (18%) and a partial response in 22 patients (34%); among responders, 76% had a duration of response (DOR) of at least 6 months and 62% had a DOR of at least 12 months.
• The FDA issued a draft guidance document to provide recommendations for designing randomized controlled clinical trials to support the accelerated approval of drugs and biologics—including conducting the trial and analyzing the data (https://www.regulations.gov/docket/FDA-2023-D-0110/document). Because single-arm trials and response endpoints, such as DOR, have limitations, randomized controlled trials are the preferred approach, the agency notes. The guidance is open for comment until May 26.
• Reuters reported that the U.S. government will not force Pfizer and Astellas to lower the price of enzalutamide (Xtandi) for the treatment of prostate cancer under its "march-in" authority, which allows the government to issue licenses to others if the patent holders accepted federal money to develop a product that is then not made available on "reasonable terms." In response to a consumer petition to the NIH, the agency said the hormone therapy is widely available and that the march-in provision wouldn't effectively lower the price. The wholesale price for enzalutamide reportedly ranges from $160,000 to $180,000 per year.

• African Americans treated for cancer who reported high levels of discrimination experienced a faster rate of aging and greater frailty than those who reported lower levels of discrimination (Cancer 2023 Mar 20 [Epub ahead of print]). The study—which included 2,232 adults who had breast, colorectal, lung, or prostate cancer diagnosed within the past 5 years—measured aging-related disease and function, as well as perceived discrimination related to employment, education, buying or renting property, and treatment by neighbors and police. Researchers found that people who reported four to seven instances of major discrimination had a large, clinically meaningful increase in age-related frailty.
• The Penn Medicine Princeton Cancer Center received a $2.5 million grant from the Bristol Myers Squibb Foundation to help fund a new geriatric oncology program. Approximately 18% of patients at the center are at least 80 years old, with needs that are different than younger patients, so they will undergo a geriatric assessment related to their overall health and social, cultural, spiritual, financial, and emotional factors. In addition, the new geriatric program aims to address the lack of older adults in clinical trials, which creates a challenge for oncologists because they don't know which new treatments are best for these patients.

• Novartis announced that the FDA approved dabrafenib (Tafinlar) with trametinib (Mekinist) for children age 1 and older with low-grade glioma with a BRAF^V600E mutation. The agency also OK'd new oral formulations of both drugs for patients who cannot swallow pills. This is the first approval of a systemic therapy as an initial treatment for children with this condition.
• Drugmakers that raised prices faster than the rate of inflation on 27 medicines will be fined, the Biden administration announced, and will have to pay back the difference to Medicare. Six of the drugs treat blood cancers: axicabtagene ciloleucel (Yescarta; Gilead), brexucabtagene autoleucel (Tecartus; Kite/Gilead), tagraxofusp (Elzonris; Menarini Group), pralatrexate (Folotyn; Acrotech Biopharma), sargramostim (Leukine; Partner Therapeutics), and pentostatin (Nipent; Pfizer). The lung cancer drug amivantamab (Rybrevant; Johnson & Johnson) and the bladder cancer drug enfortumab vedotin (Padcev; Seagen), as well as Helsinn Healthcare's netupitant/palonosetron (Akynzeo), also made the list. Medicare beneficiaries will soon see prices of these drugs reduced accordingly.
• At the annual meeting of the European Association of Urology in Milan, Italy, researchers reported that prostatectomy and radiotherapy cut the incidence of prostate cancer metastasis, local progression, and long-term use of androgen deprivation therapy in half compared with active monitoring (N Engl J Med 2023 Mar 11 [Epub ahead of print]). However, these reductions had no impact on survival after 15 years, but radical treatment was linked to urinary and bowel problems and sexual dysfunction. The data come from the ProtecT study, which enrolled 1,643 men in the UK with localized prostate cancer. Data on patients' quality of life and physical functioning were also reported (NEJM Evid 2023 Mar 11 [Epub ahead of print]).

• Researchers reported that, in patients with relapsed/refractory multiple myeloma who had already received two to four therapies, Bristol Myers Squibb's idecabtagene vicleucel (ide-cel; Abecma) significantly improved progression-free survival (PFS) compared with standard regimens (N Engl J Med 2023;388:1002–14). After a median follow-up of 18.6 months, patients who received the BCMA-directed chimeric antigen receptor T-cell therapy had a median PFS of 13.3 months compared with 4.4 months for those who received a standard drug regimen. The percentage of patients who experienced a complete response or a stringent complete response was also higher with ide-cel compared with standard regimens—39% vs. 5%, respectively.
• Clinical trial data show that immune checkpoint blockade can prompt lymph nodes to produce cancer-fighting T cells, suggesting that leaving lymph nodes near a tumor intact could boost the drugs' effectiveness (Cell 2023;186:1127–43). Instead of having immediate surgery to remove the tumor and lymph nodes, the trial's 12 patients, all of whom had head and neck cancers that hadn't metastasized beyond the lymph nodes, received one cycle of the PD-L1 inhibitor atezolizumab (Tecentriq; Genentech) prior to surgery. Examining tissue samples from before and after surgery, the researchers found greater T-cell activation in the nodes and more immune cells in the blood.

• President Joe Biden released his budget proposal for fiscal year 2024. It calls for a $503 million increase in funding for the NCI, which would bring its total budget to about $7.8 billion; it also calls for a $1 billion increase for the Advanced Research Projects Agency for Health—which would push its total funding to $2.5 billion—to fund high-risk, high-reward research on cancer, Alzheimer disease, and other diseases. The proposal indicates the president's priorities for the year and carries no force of law, as the U.S. Congress has the ultimate say in federal spending.
• Biden's budget proposal also calls for more than $11 billion to help eliminate hepatitis C as part of a 5-year program. The funding would support efforts to prevent, diagnose, and treat the virus, the main cause of liver cancer and other health problems. Former NIH Director Francis Collins, MD, PhD, coauthored a viewpoint article in support of the proposal, arguing that the expenditure "is even likely to be cost-saving, by avoiding expensive medical treatments for liver failure and liver cancer" (JAMA 2023 Mar 9 [Epub ahead of print]).
• Speaking of hepatitis, the U.S. Centers for Disease Control and Prevention called for all adults to be screened for hepatitis B infection at least once, saying that testing "is cost-effective compared with risk-based screening" because most people living with the infection don't know that they have it (MMWR Recomm Rep 2023;72:1–25). Although a cure for the condition is not available, early diagnosis and treatment of chronic infections reduce the risk of liver cancer and other conditions.

• Cofounded by Cancer Research UK and the NIH, the Cancer Grand Challenges program issued a call for research proposals on nine significant questions, the answers to which have the potential to transform cancer prevention, diagnosis, and treatment (Cancer Discov 2023 Mar 8 [Epub ahead of print]). The program, which is open to teams from around the world, will award up to $25 million to winning proposals, which are due by June 22. To learn more, visit https://cancergrandchallenges.org/new-challenges-2023.
• As of September 10, 2024, mammography facilities must tell patients whether they have dense breasts, according to a final rule issued by the FDA. Dense breast tissue makes it more difficult to spot breast cancer on a mammogram and raises the risk of developing the disease.
• An FDA advisory panel voted 11–2 in favor of approving polatuzumab vedotin (Polivy; Roche) as an initial treatment for diffuse large B-cell lymphoma—the most common type of non-Hodgkin lymphoma in the United States—based on the findings of the phase III POLARIX trial. The drug, a first-in-class anti-CD79b antibody–drug conjugate, would be combined with rituximab, an anti-CD20 monoclonal antibody, and chemotherapy. The panel's recommendation is not binding and the final decision, expected next month, rests with the FDA.
• AstraZeneca reported positive data from two trials assessing drugs to treat non–small cell lung cancer (NSCLC). In the phase III ADAURA trial, the EGFR inhibitor osimertinib (Tagrisso) significantly increased overall survival as an adjuvant therapy for early EGFR-mutant disease compared with a placebo. Also, an interim analysis of the phase III AEGEAN study showed that the PD-L1 inhibitor durvalumab (Imfinzi) combined with neoadjuvant chemotherapy followed by adjuvant durvalumab significantly improved event-free survival compared with neoadjuvant chemotherapy alone in patients with operable, early-stage NSCLC. Data will be reported at upcoming medical meetings.

• Based on the recommendation of an independent data monitoring committee, Merck discontinued its phase III KEYNOTE-641 trial, which was evaluating the PD-1 inhibitor pembrolizumab (Keytruda) combined with enzalutamide and androgen deprivation therapy (ADT) as a treatment for patients with metastatic castration-resistant prostate cancer who haven't received chemotherapy. At an interim analysis, the three-drug combo showed no improvement in radiographic progression-free survival (PFS) or overall survival (OS) compared with an enzalutamide/ADT regimen.
• Merck also announced that another study evaluating pembrolizumab didn't meet its primary endpoints. In the final analysis of the phase III KEYNOTE-789 trial, there was no statistically significant improvement in OS compared with chemotherapy in patients with metastatic nonsquamous non–small cell lung cancer (NSCLC) harboring EGFR mutations who already tried a tyrosine kinase inhibitor, including osimertinib (Tagrisso; AstraZeneca). Although an earlier analysis showed improvement in PFS, the results weren't statistically significant either.
• The news wasn't all bad for Merck. The company announced that the phase III KEYNOTE-671 trial of pembrolizumab met a primary endpoint—event-free survival—as part of a perioperative treatment regimen for patients with stage II, IIIA, or IIIB NSCLC, compared with neoadjuvant chemotherapy plus a placebo followed by an adjuvant placebo. Based on the data, which will be presented at an upcoming medical meeting, the FDA will consider approving pembrolizumab for this indication; a decision is expected by mid-October.

• The combination of cabozantinib (Cabometyx; Exelixis) and the PD-L1 inhibitor atezolizumab (Tecentriq; Roche/Genentech) did not meet its primary endpoint of PFS versus cabozantinib alone in patients with locally advanced or metastatic clear-cell or non–clear cell renal cell carcinoma (RCC) whose disease progressed during or after the use of immune checkpoint inhibitors, Exelixis and Roche announced. A multi–receptor tyrosine kinase inhibitor, cabozantinib is FDA approved to treat RCC in other situations. Detailed findings will be presented at an upcoming medical meeting.
• On behalf of the Environmental Protection Agency, the U.S. Department of Justice filed a complaint against Denka Performance Elastomer to force the company "to significantly reduce hazardous chloroprene emissions from its neoprene manufacturing facility in LaPlace, LA," which borders a majority-Black community. According to the FDA, the plant's "operations present an imminent and substantial endangerment to public health and welfare due to the cancer risks" posed by chloroprene emissions. Air monitoring has shown that concentrations of chloroprene in the air near the facility have been "as high as 14 times the levels recommended for a 70-year lifetime of exposure."
• Citing a lack of evidence, a U.S. District Court judge dismissed a lawsuit brought by Celgene investors accusing Bristol Myers Squibb (BMS) of fraud, Reuters reported. As agreed when BMS bought Celgene in 2019, stockholders would receive about $6.4 billion if lisocabtagene maraleucel (Breyanzi) and two other drugs garnered FDA approval by a set deadline; investors said that BMS failed to submit key information to the FDA in a timely manner, thus delaying the approvals and missing the deadline. Two similar suits are still pending.

• AstraZeneca announced that the European Commission approved regimens of durvalumab (Imfinzi) and tremelimumab (Imjudo) for advanced liver and lung cancers. The approval of the CTLA4 and PD-L1 inhibitor duo as a first-line therapy for advanced or inoperable hepatocellular carcinoma was based on the phase III HIMALAYA trial, in which median overall survival (OS) was 16.4 months compared with 13.8 months with sorafenib (Nexavar; Bayer), a multikinase inhibitor (NEJM Evid 2022;1(2):EVIDoa2100070). The immunotherapy combination plus chemotherapy was approved for metastatic non–small cell lung cancer based on the phase III POSEIDON trial, in which median OS was 14 months compared with 11.7 months for chemotherapy alone (J Clin Oncol 2023;41:1213–27).
• Cambridge, MA–based Jounce Therapeutics announced that it will lay off 57% of its staff. Clinical studies of its JTX-8064 and vopratelimab—an LILRB2 (ILT4) receptor antagonist shown to reprogram immune-suppressive tumor-associated macrophages to an antitumor state and a mAb that binds to and activates ICOS, respectively—have not demonstrated sufficient clinical activity to move forward without additional funding. The company also announced that it will merge with the UK's Redx, which aims to discover and develop novel, small-molecule, targeted therapeutics to treat cancer and fibrotic diseases and cancer-associated fibrosis.

• Actinium Pharmaceuticals announced that Iomab-B met its primary endpoint of durable complete remission (dCR) of 6 months following initial complete remission after bone marrow transplant—22% of patients with active relapsed/recurrent acute myeloid leukemia achieved a dCR compared with 0% in the control arm. In patients who had a dCR, 92% survived at least 1 year. Iomab-B is a mAb that targets blood cancer cells and stem cells that overexpress CD45 in bone marrow; the radioactive isotope iodine-131, which is connected to the antibody, kills the cells.
• The FDA filed civil money penalty complaints against four tobacco companies for manufacturing and selling e-liquids without marketing authorization; e-liquids are used in electronic cigarettes and vaping devices to give the vapor that users inhale its flavoring and nicotine. This is the first time the agency has filed such complaints, which carry a maximum penalty of $19,192 per violation, against tobacco product manufacturers. The cited companies are BAM Group, Great American Vapes, Vapor Corner, and 13 Vapor.
• Sixty-five percent of Americans are not up to date with screening for at least one type of cancer—breast, cervical, colorectal, oral, lung, prostate, skin, or testicular—according to a survey of 2,014 people age 25 and older conducted by the Prevent Cancer Foundation. Survey respondents said they were not current with screenings due to not knowing they needed to be screened (39%), not having symptoms (37%), and inability to cover any associated costs (31%).

• When combined with the antiandrogen enzalutamide, the PARP inhibitor talazoparib (Talzenna; Pfizer) significantly improved progression-free survival (PFS) for men with metastatic, castration-resistant prostate cancer (mCRPC) compared with enzalutamide alone, according to data presented at the 2023 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium in San Francisco, CA. In the TALAPRO-2 trial, which included 805 men, median PFS was 37% better with talazoparib, and although the data aren't mature, researchers observed a trend toward longer overall survival (OS). Improvements were seen regardless of homologous recombination repair status.
• Also at the ASCO conference, researchers reported that rucaparib (Rubraca; Clovis Oncology) demonstrated a trend toward improved OS compared with physician's choice of treatment in patients with chemotherapy-naive mCRPC and BRCA1/2 alterations in an interim assessment of data from the phase III TRITON3 trial. In the subgroup of patients with BRCA mutations, OS was 24.3 months with rucaparib vs. 20.8 months with physician's choice; in the intention-to-treat population, OS was 23.6 months and 20.9 months, respectively. A concurrently published article reported significant improvements in PFS in the phase II portion of the trial (N Engl J Med 2023 Feb 16 [Epub ahead of print]).
• Blueprint Medicines announced that the FDA placed a partial clinical hold on a phase I/II trial of BLU-222 in patients with advanced solid tumors due to reversible light sensitivity and blurred vision "in a limited number of patients." Blueprint will investigate the adverse events—all cases were grade 1 except one grade 3 reaction—and amend the study protocol to aid investigators in monitoring for and managing these side effects. Although no additional patients will be enrolled in the trial until after that happens, patients currently enrolled in the VELA trial can continue to receive the CDK2 inhibitor.

• Soligenix announced that the FDA will not accept the company's application for approval of synthetic hypericin (SGX301; HyBryte) for the treatment of early-stage cutaneous T-cell lymphoma because it was "not sufficiently complete to permit substantive review." The agent is a first-in-class photodynamic therapy that's applied to skin lesions and is taken up by malignant T cells and then activated by visible light in the red–yellow spectrum. The company says it will meet with FDA officials to determine what information needs to be supplied.
• The governing board of the Cancer Prevention & Research Institute of Texas (CPRIT) doled out more than $90 million in new cancer research and prevention grants to fund 40 research ventures and prevention efforts across the state. The money will cover expenses related to, among other things, studying and addressing disparities in cancer treatment and mortality, fighting cancer in children and teens, and recruiting top-notch researchers. Formed by the Texas legislature—and supported by voters—CPRIT has awarded more than $6 billion for cancer research and prevention since 2007.

• During his State of the Union address, U.S. President Joe Biden iterated his commitment to "cut the cancer death rates at least by 50% in the next 25 years" and "turn more cancers from death sentences to treatable diseases." He referenced the effort by President George W. Bush to "transform the global fight" against human immunodeficiency virus/acquired immune deficiency syndrome, saying, "It's been a huge success. He thought big, he thought large. He moved. I believe we can do the same thing with cancer."
• By an 8–5 vote, an FDA advisory panel said that two single-arm trials would be sufficient to show the risks and potential benefits of dostarlimab (Jemperli; GSK) for the treatment of patients with mismatch repair–deficient (dMMR)/microsatellite instability–high locally advanced rectal cancer. In an initial study, the PD-1 inhibitor elicited a 100% clinical complete response rate with no serious side effects (N Engl J Med 2022;386:2363–76). Several panel members said researchers would have difficulty enrolling patients in a randomized trial comparing dostarlimab to chemotherapy, radiation, and surgery given the drug's impressive efficacy and the potential adverse effects of the other treatments.
• The same day, the FDA granted regular approval to dostarlimab for adults with dMMR recurrent or advanced endometrial cancer that has progressed on or after the use of chemotherapy. (The PD-1 inhibitor received accelerated approval for this indication in 2021.) Efficacy for the regular approval was demonstrated in the 141-patient GARNET trial: The confirmed overall response rate was 45.4% with a 15.6% complete response rate; the median duration of response was not reached, but 85.9% of patients experienced responses lasting at least 1 year.

• Kite announced that brexucabtagene autoleucel (Tecartus) yielded a median overall survival of 26 months and an overall survival rate of 47.1% in adults with relapsed/refractory B-cell acute lymphoblastic leukemia at the 3-year follow-up in the phase II ZUMA-3 study. The chimeric antigen receptor T-cell therapy also elicited a strong durable response—the rate of complete remission and complete remission with incomplete hematologic recovery was 71%.
• In a survey conducted between June and November 2020, 4,266 patients reported that they planned to have at least one cancer screening, but many of them delayed it due to concerns about testing during the COVID-19 pandemic (J Clin Oncol 2023 Feb 3 [Epub ahead of print]). Of those eligible for particular screenings, 24% postponed a mammogram, 27% put off a Pap test, 27% delayed a human papillomavirus test, 11% postponed a stool blood test, and 36% delayed a colonoscopy.
• Reuters reported that Illumina pressed its case for the takeover of Grail with "senior European and national antitrust officials at a closed hearing to argue against an EU antitrust order that it divests" itself from Grail, which makes tests to detect cancer. Illumina completed the takeover in 2021 but didn't obtain regulatory approval from the EU, which subsequently ordered the deal to be undone due to concerns that the merger "would stifle innovation." According to Reuters, Illumina has argued that the European Commission should not have involved itself in the case because "the companies do not meet a revenue threshold stipulated by EU merger rules" and because the deal would encourage competition.

• The FDA approved the first oral selective estrogen receptor (ER) degrader, elacestrant (Orserdu; Stemline Therapeutics), for patients with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast after they've tried at least one endocrine therapy regimen. The approval was based on the EMERALD trial, in which 228 patients with the mutations who received elacestrant experienced a median progression-free survival (PFS) of 3.8 months compared with 1.9 months in patients who received fulvestrant or an aromatase inhibitor. The agency also approved the Guardant360 CDx assay to identify patients with ESR1 mutations.
• In addition, the FDA approved sacituzumab govitecan (Trodelvy; Gilead) for patients with hormone receptor–positive, HER2-negative breast cancer who have received endocrine-based therapy and at least two other systemic therapies. The decision was based on findings of the TROPiCS-02 study, which compared sacituzumab govitecan with single-agent chemotherapy: The median PFS was 5.5 months and 4 months, respectively; median overall survival was 14.4 months and 11.2 months, respectively. The drug, which was already approved for urothelial cancer, is a Trop-2–directed antibody and topoisomerase inhibitor conjugate.
• Accelerated approval was granted to pirtobrutinib (Jaypirca; Eli Lilly) by the FDA for relapsed/refractory mantle cell lymphoma following the use of at least two systemic therapies, including a Bruton tyrosine kinase (BTK) inhibitor. In the BRUIN trial, which involved 120 patients, the overall response rate was 50%, with a complete response rate of 13%; the estimated median duration of response (DOR) was 8.3 months, and the estimated DOR at 6 months was 65.3%. Pirtobrutinib is a BTK inhibitor.

• In a presentation of its financial data for 2022, Roche revealed that it will discontinue development of ipatasertib, an AKT inhibitor. The investigational agent was being assessed in a phase III trial in men with castration-resistant prostate cancer. The company also noted that it will nix development of efmarodocokin alfa for the treatment of acute graft-versus-host disease.
• STAT reported that the Third Circuit U.S. Court of Appeals rejected Johnson & Johnson's use of Chapter 11 bankruptcy to freeze tens of thousands of lawsuits claiming that the company's talc products led to the development of cancer in users. The company had created a subsidiary called LTL Management with limited financial resources to handle the lawsuits in bankruptcy court, thus shielding itself from trials and monetary awards.
• Nearly a year ago, City of Hope in Duarte CA, acquired Cancer Treatment Centers of America (CTCA). Those centers now officially share the City of Hope name, with locations called City of Hope Atlanta in Georgia, City of Hope Chicago in Illinois, and City of Hope Phoenix in Arizona. The CTCA locations have become nonprofit entities as well.

• Guardant Health laid off about 7% of its staff. The decision was made, the company said, to "better support both our near- and long-term growth as well as out path to profitability. This decision puts us in an even better position to deliver on the promise we made ten years ago to transform cancer care." The company makes the Guardant360 assay and blood tests to help inform treatment decisions, monitor treatment response, and detect recurrent/residual disease.
• Merck announced that the FDA approved pembrolizumab (Keytruda) for certain cases of non–small cell lung cancer (NSCLC)—namely those requiring adjuvant treatment following surgery and platinum-based chemotherapy for stage IB, II, or IIIA disease. Efficacy was evaluated in the KEYNOTE-091 trial, with patients experiencing a statistically significant improvement in median disease-free survival compared with those who received a placebo—58.7 months vs. 34.9 months. A PD-1 inhibitor, pembrolizumab is FDA approved for dozens of indications in 16 types of cancer.
• However, Merck stopped its KEYNOTE-991 trial evaluating pembrolizumab in certain prostate cancers based on the recommendation of an independent data monitoring committee. The drug, given in combination with enzalutamide and androgen deprivation therapy (ADT), was unlikely to demonstrate an improvement in overall survival (OS) compared with placebo, enzalutamide, and ADT in patients with metastatic hormone-sensitive disease. Data from the study will be presented at an upcoming medical meeting.
• Magenta Therapeutics paused its phase I/II dose escalation trial of MGTA-117 following the death of a patient from respiratory failure and cardiac arrest that might be related to the agent. MGTA-117 is an antibody–drug conjugate designed to deplete CD117-expressing cells in blood and/or bone marrow prior to a stem cell transplant or receiving an ex vivo gene therapy product. The company says it has reported the death to the FDA and will "evaluate the totality of available data and determine next steps for the development of MGTA-117."

• AstraZeneca (AZ) and Daiichi Sankyo's trastuzumab deruxtecan (Enhertu) was approved in the European Union for adults with inoperable or metastatic HER2-low breast cancer who received chemotherapy for metastatic disease and experienced recurrence during or within 6 months of treatment. The decision was based on the results of the DESTINY-Breast04 trial, in which the drug reduced the risk of disease progression or death by 50% and increased OS by more than 6 months compared with chemotherapy (N Engl J Med 2022;387:9–20). The drug has already been approved by the FDA for this indication.
• In other AZ news, Bristol Myers Squibb (BMS) filed a lawsuit against the company claiming that AZ's CTLA4 inhibitor tremelimumab (Imjudo) infringes on two patents that cover BMS's CTLA4 inhibitor ipilimumab (Yervoy). Tremelimumab received FDA approval in October to treat hepatocellular carcinoma and in November to treat NSCLC.
• The FDA denied marketing of two Vuse menthol electronic cigarette products on the grounds that marketing applications from the R.J. Reynolds Vapor Company "lacked sufficient evidence to demonstrate that permitting the marketing of the products would be appropriate for the protection of the public health." The company must stop selling the products—the Vuse Vibe Tank Menthol 3.0% and the Vuse Ciro Cartridge Menthol 1.5%—or "risk FDA enforcement action."

• The FDA granted accelerated approval to tucatinib (Tukysa; Seagen) in combination with trastuzumab for certain cases of inoperable RAS wild-type, HER2-positive metastatic colorectal cancer based on results of a phase II trial. In 84 patients who had previously received chemotherapy and a VEGF mAb, the HER2 inhibitor duo yielded an overall response rate (ORR) of 38% and a duration of response (DOR) of 12.4 months. The most common side effects were diarrhea, nausea, vomiting, rash, and hepatotoxicity.
• BeiGene announced that the agency approved zanubrutinib (Brukinsa) for chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) based on the results of two phase III trials of the BTK inhibitor. In one trial of 479 patients newly diagnosed with CLL or SLL, the median progression-free survival was not reached with zanubrutinib but was 33.7 months in a cohort of patients who received bendamustine plus rituximab after a median follow-up of 25 months. In a separate trial, 652 patients received either zanubrutinib or ibrutinib (Imbruvica; Pharmacyclics/Janssen). The ORR was 80% with zanubrutinib and 73% with ibrutinib; the median DOR was not reached after a median follow-up of 14.1 months.
• Researchers found that the quality of care for early-stage non–small cell lung cancer varies widely across the United States (JAMA Surg 2023 Jan 18 [Epub ahead of print]). The team examined data from 9,628 patients who were treated at U.S. Veterans Health Administration (VA) hospitals and 107,674 nonveteran patients treated at civilian hospitals. They found poor adherence to five quality metrics at both VA and civilian hospitals—for example, only about one third of patients received adequate lymph node sampling, and only about 40% had minimally invasive surgery.

• At the 2023 American Society of Clinical Oncology Gastrointestinal Cancers Symposium in San Francisco, CA, researchers reported that in the phase III SUNLIGHT study, Taiho Oncology's trifluridine/tipiracil (Lonsurf) plus bevacizumab improved overall survival by 3.3 months in patients with refractory metastatic colorectal cancer who experienced disease progression or intolerance after least two chemotherapy regimens compared with trifluridine/tipiracil alone—10.8 months and 7.5 months, respectively. The improvement represents a 39% reduction in the risk of death. The drug is approved by the FDA to treat metastatic colorectal cancer, as well as gastric and gastroesophageal junction cancers.
• Citing misinformation, conspiracy theories, and inappropriate responses to its tweets, the Finnish Institute for Health and Welfare (THL) has stopped using its Twitter account, pharmaphorum reported. The decision follows Twitter's announcement that it will no longer enforce a policy prohibiting posting misleading and incorrect information about SARS-CoV-2. THL, which reportedly has almost 95,000 Twitter followers, is an R&D institute that provides research-based health information; it's part of the country's Ministry of Social Affairs and Health.

• In its annual report on cancer cases and mortality, the American Cancer Society highlighted a 33% reduction in cancer deaths overall since 1991, which was helped by a 1.5% decline between 2019 and 2020, translating into about 3.8 million lives saved (CA Cancer J Clin 2023 Jan 12 [Epub ahead of print]). Improved treatment of leukemia, melanoma, kidney cancer, and lung cancer drove the decrease in mortality. However, the report noted that the incidence of breast, prostate, and uterine cancers is on the rise, which could slow the rate of decline in deaths in years to come.
• Researchers reported that older Black patients were 4.3% less likely than white patients to receive any opioid for cancer pain and 3.2% less likely to receive long-acting opioids, with similar differences between Hispanic and white patients, in the last weeks of life (J Clin Oncol 2023 Jan 10 [Epub ahead of print]). That finding was based on opioid prescriptions for more than 318,000 patients with cancer reported to Medicare between 2007 and 2019. Due to tightening restrictions on opioid access, fewer patients have been receiving the drugs—by 2019, only 32.7% of patients overall received any opioid and just 9.4% were given a long-acting version—so the differences translate into a clinically meaningful amount of pain management.

• In a regular communiqué of drug shortages, the FDA noted that AstraZeneca will discontinue moxetumomab pasudotox (Lumoxiti), a CD22-directed cytotoxin, by the end of August. The drug was approved for certain cases of hairy cell leukemia in 2018. In a letter to health care providers, the company noted that the drug hasn't been readily used, perhaps because it's more difficult to administer and because other treatments are available.
• STAT reported that, for the second time, the U.S. Supreme Court declined to consider a suit filed by Bristol Myers Squibb (BMS) calling for a $1.2 billion settlement against Gilead and its subsidiary Kite to be reinstated. The case involved a dispute over Gilead's axicabtagene ciloleucel (Yescarta), with BMS claiming that its subsidiary Juno held the patent. In 2021, the U.S. Court of Appeals for the Federal Circuit overturned the settlement, calling Juno's patent invalid.
• Afamitresgene autoleucel (afami-cel) demonstrated significant effectiveness in a phase I trial that included 38 patients with several types of solid tumors (Nat Med 2023 Jan 9 [Epub ahead of print]). An adoptive T-cell receptor therapy targeting the MAGE-A4 cancer antigen, afami-cel proved particularly effective in a subgroup of 16 patients with synovial sarcoma—their overall response rate was 44%, whereas the response rate across all tumor types was 24%. All patients in the trial experienced adverse events, with low blood cell counts being the most common, but the findings could be good news for patients with synovial sarcoma because they have few treatment options following chemotherapy.

• Genentech announced that the FDA granted accelerated approval to mosunetuzumab (Lunsumio) to treat adults with certain follicular lymphomas (FL). A bispecific CD20-directed CD3 T-cell engager, mosunetuzumab was tested in an open-label, multicenter, multicohort study involving 90 patients with relapsed/refractory FL after at least two systemic drug regimens, including an anti-CD20 mAb and an alkylating agent. The overall response rate was 80%, with 60% achieving complete responses; after a median follow-up of 14.9 months among responders, the estimated median duration of response was 22.8 months. The drug carries a boxed warning for serious or life-threatening cytokine release syndrome.
• PDS Biotechnology reported that the PDS0101-based triple combination therapy yielded a median overall survival (OS) of 21 months in 29 patients with advanced human papillomavirus 16 (HPV16)–positive cancers of the anus, cervix, head and neck, vagina, and vulva refractory to immune checkpoint inhibitors; the historical median OS in such patients is 3 to 4 months. The three-drug combination includes PDS0101, which activates CD4⁺ helper T cells and CD8⁺ natural killer cells; the tumor-targeting IL12 fusion protein M9241 (Merck); and bintrafusp alfa (Merck), which targets the PD-L1 and TGFβ pathways.

• Novocure announced that Tumor Treating Fields (TTFields) and standard therapy demonstrated a statistically significant and clinically meaningful improvement in OS compared with standard therapy alone in patients with stage IV non–small cell lung cancer that worsened while on or after treatment with platinum-based chemotherapy. In releasing the top-line results for the pivotal, open-label, randomized LUNAR trial, Novocure also noted a statistically significant and clinically meaningful improvement in OS in patients treated with TTFields—described by the company as "electric fields that exert physical forces to kill cancer cells through a variety of mechanisms"—and immune checkpoint inhibitors. Full data will be presented at a future medical meeting.
• COVID-19 vaccine maker BioNTech signed a deal with the UK government to treat up to 10,000 patients with personalized mRNA cancer immunotherapies by the end of 2030. The company will use the UK's clinical trial network and genomic and health data to accelerate its work—and aims to enroll the first patient in a clinical trial by the end of this year. According to Bloomberg, the deal could be worth up to $750 million over 8 to 10 years.
• In a deal valued at $35 million—with as much as $1.2 billion more in milestone payments—COVID-19 vaccine maker Moderna will collaborate with CytomX to develop investigational mRNA-based conditionally activated therapies for cancer and other diseases. The companies will combine Moderna's experience in the science, delivery, and manufacturing of mRNA therapies with CytomX's Probody technology, which allows proteins to be "activated locally in disease tissue while remaining masked in systemic circulation." Last month, Moderna announced that an mRNA vaccine demonstrated efficacy against skin cancer.