The anti-CD38 monoclonal antibody daratumumab (Darzalex; Janssen) significantly reduces the risk of smoldering multiple myeloma progressing to active multiple myeloma , according to research presented at the American Society of Hematology Annual Meeting and Exposition, held December 7–10 in San Diego, CA, and published concurrently ( N Engl J Med 2024 Dec 9 [Epub ahead of print] ). In the phase III AQUILA study, 390 patients with high-risk smoldering multiple myeloma received either subcutaneous daratumumab––which is approved to treat active multiple myeloma––or active monitoring. Daratumumab was associated with a 51% lower risk of disease progression or death compared with active monitoring. Among all participants, progression-free survival, the trial’s primary endpoint, was 63.1% in the daratumumab group and 40.8% in the active monitoring group at 5 years; overall survival was 93% and 86.9%, respectively.

At the American Society of Hematology Annual Meeting and Exposition in San Diego and in a simultaneously published article, researchers reported that adding blinatumomab (Blincyto; Amgen) to chemotherapy significantly improved disease-free survival in children newly diagnosed with standard-risk B-cell acute lymphoblastic leukemia (ALL; N Engl J Med 2024 Dec 7 [Epub ahead of print] ). In the phase III AALL1731 trial, 1,440 children with the condition at average or high risk of relapse received either chemotherapy plus the anti-CD19/anti-CD3 bispecific T-cell engager or chemotherapy alone. Overall, after a median follow-up of 2.5 years, the estimated 3-year disease-free survival rate was 96% among those who received blinatumomab and 87.9% among those who received only chemotherapy. Because relapsed B-cell ALL is a leading cancer-related cause of death in children, meeting attendees greeted the news with cheers and enthusiastic applause. Further, based on the strength of these results, the data and safety monitoring committee recommended halting further enrollment in the trial.

At the Annual Meeting of the Society of Urologic Oncology, Protara Therapeutics announced that TARA-002 showed high response rates in patients with non–muscle invasive bladder cancer who do not respond to, or have not been treated with, Bacillus Calmette-Guerin therapy, which is part of the current standard treatment for this cancer. TARA-002 contains an inactivated form of the Streptococcus pyogenes bacterium suspected to activate immune cells that elicit an inflammatory response lethal to tumor cells. In the phase II ADVANCED-2 study, 13 of 18 patients (72%) maintained a complete response (CR) at 6 months, while 100% of patients maintained a CR from 3 to 6 months.

The FDA approved durvalumab (Imfinzi; AstraZeneca) and zenocutuzumab (Bizengri; Merus) for limited-stage small cell lung cancer (LS-SCLC) and NRG1 -positive non–small cell lung cancer or pancreatic adenocarcinoma, respectively. In the phase III ADRIATIC study, which supported durvalumab’s approval, median overall survival was 55.9 months for patients receiving durvalumab and 33.4 months for those receiving a placebo. Zenocutuzumab, a HER2xHER3 bispecific antibody, received accelerated approval based on the phase I/II, single-agent eNRGy study. For patients with NSCLC, the overall response rate (ORR) was 33% and the median duration of response (DOR) was 7.4 months; for those with pancreatic adenocarcinoma, the ORR was 40% and the DOR ranged from 3.7 months to 16.6 months.

The Supreme Court of the United States (SCOTUS) heard arguments on whether the FDA unlawfully rejected two companies’ applications to sell flavored liquids for use in electronic cigarettes (e-cigarettes). Under federal law, manufacturers of tobacco products and e-cigarettes, which heat a liquid to create an aerosol that is inhaled, are required to obtain FDA authorization before selling a new product. The FDA had determined that the fruit and candy flavors in the products may encourage young people to become addicted to nicotine and expressed uncertainty that they would help adults who already smoke to quit. The companies, Triton Distribution and Vapetasia, argued that the FDA unfairly introduced new requirements for approval, a claim most of the justices seemed to find suspect during yesterday’s oral arguments. A decision is expected by the end of June.

Novocure announced today that its Tumor Treating Fields (TTFields) therapy extended survival in patients with pancreatic adenocarcinoma . In the phase III PANOV-3 study, patients with inoperable, locally advanced disease treated with TTFields and chemotherapy had a median overall survival (OS) of 16.2 months, compared with 14.2 months for those receiving only chemotherapy, making PANOVA-3 the first phase III trial to demonstrate a statistically significant benefit (OS) for this type of cancer, according to the company. TTFields delivers electric currents through pads worn over the skin near the tumor to disrupt the growth of cancer cells and is approved to treat glioblastoma and mesothelioma.

President-elect Donald Trump announced he will nominate Jay Bhattacharya , MD, PhD, of the Stanford University School of Medicine in California, to head the NIH. A professor of health policy, Bhattacharya has argued that COVID-19 lockdowns caused irreparable harm to public health; instead, he has promoted herd immunity through natural infection of younger people as the best way to protect those most vulnerable. In addition, Trump nominated Robert Kennedy Jr., a vaccine skeptic, to lead the U.S. Department of Health and Human Services, and Martin Makary, MD, and Dave Weldon, MD, to lead the FDA and Centers for Disease Control and Prevention, respectively, both of whom have been critical of vaccine mandates and the agencies they’ve been selected to lead.

San Diego, CA–based Poseida Therapeutics, which specializes in developing allogeneic chimeric antigen receptor (CAR) T-cell therapies that use stem cell memory T cells (T SCM ), announced today it will be acquired by Roche in a deal valued at approximately $1.5 billion. T SCM are the least differentiated type of memory T cells and are long-lived and self-replicating, which can improve the safety and efficacy of CAR T-cell therapy. In a phase I/Ib study, Poseida’s P-BCMA-ALL01 led to a 91% overall response rate in patients with relapsed or refractory multiple myeloma; Roche and Poseida began jointly developing the therapy before the acquisition.

For adults ages 27 to 45, vaccinating against human papillomavirus (HPV) is costlier and less effective than vaccinating younger people to prevent HPV-related cancers ( Ann Intern Med 2024 Nov 26 [Epub ahead of print] ). Researchers found that 7,650 people ages 27 to 45 would need to be vaccinated to prevent one HPV-related cancer, compared with 223 people ages 9 to 26. Women ages 27 to 45 who recently separated from a long-term sexual partner and have a higher number of lifetime partners, who are at higher risk of developing new HPV infections, stand to benefit from HPV vaccination more than other subgroups in the age range. The potential additional benefits of vaccination for people ages 27 to 45 are limited because vaccination of people ages 26 and younger has led to the emergence of herd immunity, according to the researchers.

Treatment with eflornithine led to clinically meaningful improvements in overall survival (OS) and progression-free survival (PFS) for patients with recurrent grade 3 IDH -mutant astrocytoma, an aggressive brain tumor composed of astrocytes. In the phase III STELLAR study, of the 194 patients with this type of astrocytoma, those who received eflornithine plus chemotherapy had an OS of 34.9 months, compared with 23.5 months for those who received chemotherapy alone; PFS was 15.8 months and 7.2 months, respectively. Eflornithine inhibits the ornithine decarboxylase, an enzyme in mammalian polyamine biosynthesis that’s upregulated in certain cancers.

The FDA approved zanidatamab (Ziihera; Jazz Pharmaceuticals) for previously treated, inoperable, or metastatic HER2- positive biliary tract cancer (BTC), which targets two distinct HER2 epitopes and is the first dual HER2- targeted bispecific antibody to be approved in the United States for this condition. The decision to approve zanidatamab was based on results of the single-arm, phase IIb HERIZON-BTC-01 study, in which 32 of 62 patients (52%) responded to the drug; the median duration of response was 14.9 months. The diagnostic device VENTANA PATHWAY anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody (Ventana Medical Systems/Roche) was also approved to aid in identifying promising candidates for zanidatamab.

For the third time, England’s National Institute for Health and Care Excellence ( NICE) failed to agree on a price for trastuzumab deruxtecan (T-DXd; Enhertu) with AstraZeneca and Daiichi Sankyo, keeping the companies’ antibody–drug conjugate out of reach for women in England, Wales, and Northern Ireland with HER2 -low metastatic breast cancer. Accordingly, NICE guidance continues to say that T-DXd is not a cost-effective therapy for the National Health Services to cover, the first breast cancer treatment NICE has been unable to recommend in 6 years. T-DXd received FDA approval for HER2-low metastatic breast cancer treated with a prior systemic therapy in August 2022; it’s approved for this indication in more than 55 countries.

Merck announced today that pembrolizumab (Keytruda) injected subcutaneously is not inferior to intravenous (IV) dosing, currently the drug’s only approved route of administration. In the phase III MK-3475A-D77 trial, researchers found that patients with metastatic non–small cell lung cancer who received pembrolizumab plus chemotherapy had similar blood plasma concentrations of the PD-1 inhibitor regardless of how it was given. Detailed results will be presented at an upcoming medical meeting and shared with regulatory authorities. Merck’s patent on IV pembrolizumab, which generated $25 billion in sales in 2023, will expire in 2028, but the subcutaneous form of the drug would extend its patent protection.

The FDA approved revumenib (Revuforj; Syndax Pharmaceuticals), the first menin inhibitor ever greenlighted by the agency, for adults and children with relapsed or refractory acute leukemia with a KMT2A translocation. KMT2A translocations cause an overexpression of genes involved in blood cell production and are associated with aggressive forms of pediatric and adult leukemia. Menin is a protein required for the oncogenic function of KMT2A fusions in leukemia. The decision was based on results of the single-arm, phase I/II AUGMENT-101 trial, in which 21% of 104 patients achieved a complete remission (CR) or CR with partial hematologic recovery; the median duration of response was 6.4 months.

Bristol Myers Squibb (BMS) faces a $6.7 billion lawsuit alleging that the company purposely delayed approval of Celgene-developed drugs to avoid paying Celgene shareholders owning contingent value rights (CVR), according to Reuters. An earlier suit, brought for $6.4 billion, was dismissed in late September on the grounds that the plaintiff, UMB Bank, was never properly appointed to represent the owners of CVRs and therefore lacked standing. CVRs are awarded to shareholders of a company being acquired; when BMS acquired Celgene in 2019, it guaranteed investors an additional payout pending FDA approval of three Celgene drugs, but the approval deadline was not met for lisocabtagene maraleucel (Breyanzi), a gene therapy for non-Hodgkin lymphoma. UMB Bank said it had addressed the judge’s concerns and been confirmed as a trustee, enabling the suit to proceed.

GSK announced that its antibody–drug conjugate (ADC) belantamab mafodotin (Blenrep) led to significantly better survival outcomes in patients with multiple myeloma than daratumumab (Darzalex; Johnson & Johnson) in the phase III DREAMM-7 study, nearly 2 years after the drug was pulled from the market for failing to show superiority over a standard treatment in an earlier phase III trial. In DREAMM-7, both drugs were administered in combination with bortezomib plus dexamethasone and as a second-line or later treatment. This follows encouraging results released in June that showed patients receiving GSK’s drug had a 60% greater reduction in risk of death or disease progression compared with those taking daratumumab. Data from the trial will be presented at next month’s American Society of Hematology annual meeting.

Today, Merck announced that it will acquire LaNova Medicines’ PD-1/VEGF bispecific antibody, LM-299, for $588 million upfront plus financial awards that could reach $2.7 billion if certain development and commercialization milestones are reached. Merck will receive the exclusive right to develop, manufacture, and commercialize LM-299, which demonstrated strong inhibition of tumor growth in humanized mice in preclinical studies. A phase I trial for LM-299 is currently enrolling patients in China, and a U.S.-based phase I trial is expected to launch soon.

Cambridge, MA–based biotech Flare Therapeutics will collaborate with Roche to develop cancer therapeutics that target transcription factors. Roche will pay Flare $70 million in cash up front—and financial awards that could exceed $1.8 billion if certain development milestones are reached—plus royalties. Under the partnership Flare will share its proteomics and mass spectrometry platform and its library of electrophiles, which enable the identification of druggable regions within cancer-related transcription factors.  For example, Flare’s lead candidate, FX-909, under evaluation in a phase I trial, inhibits a transcription factor implicated in urothelial carcinoma; the biotech will maintain ownership of the drug along with the rest of its existing pipeline.

Autolus Therapeutics’ chimeric antigen receptor (CAR) T-cell therapy obecabtagene autoleucel (Aucatzyl) received FDA approval for adults with B-cell precursor acute lymphoblastic leukemia (ALL). The decision was based on results from the phase Ib/II FELIX study, a single-arm trial that enrolled patients with CD19-positive B-cell relapsed or refractory ALL. Of the 65 evaluable patients, 27 (42%) achieved complete remission within 3 months of infusion; the median duration of remission was 14.1 months. Neurotoxicity was observed in 64% of patients, 12% of whom experienced adverse events of grade 3 or higher.

According to research presented at the Society for the Immunotherapy of Cancer Annual Meeting in Houston, TX, the IL15 agonist NKTR-255 (Nektar Therapeutics) reverses lymphopenia caused by chemoradiation therapy (CRT), which can hinder the effectiveness of immunotherapies. In a phase II study, nine of 15 patients with locally advanced non–small cell lung cancer who received NKTR-255 along with the monoclonal antibody durvalumab (Imfinzi; AstraZeneca) after CRT had normal lymphocyte levels after 8 weeks of treatment. In contrast, there was no statistically significant lymphocyte restoration in the patients who received durvalumab alone.