5 Key Oncology FDA Approvals From November

November saw numerous FDA approvals across the health care continuum, including several in oncology. These approvals cover treatments for hematologic cancers, non-small cell lung cancer (NSCLC), muscle-invasive bladder cancer (MIBC), and gastric and gastroesophageal junction cancers.

Here are 5 notable oncology FDA approvals from last month:

FDA Approves Daratumumab and Hyaluronidase-fihj for High-Risk MM

During the first week of November, the FDA approved daratumumab and hyaluronidase-fihj (Darzalex Faspro; Janssen Biotech Inc) as a subcutaneous monotherapy for adults with high-risk smoldering multiple myeloma (MM).¹ The recommended dose is 1800 units of daratumumab and 30,000 units of hyaluronidase-fihj, with administration expected to take 3 to 5 minutes.

The approval was based on data from the ongoing phase 3 AQUILA trial (NCT03301220), which randomized 390 patients 1:1 to receive daratumumab and hyaluronidase-fihj on a weekly, biweekly, and monthly schedule or active monitoring, with follow-up for up to 3 years. Data presented at last year’s American Society of Hematology Annual Meeting and Exposition showed significant reductions in the risk of smoldering MM progressing to active disease with treatment.²

Patients in the treatment arm had a 63.1% progression-free survival rate, compared with 40.8% in the active monitoring cohort; 5-year overall survival rates were 93.0% and 86.9%, respectively. Although median time to frontline treatment was not reached for the treatmenet arm, it was 50.2 months for the active monitoring arm (HR, 0.46; 95% CI, 0.33-0.62; P < .0001).

The FDA had previously approved daratumumab and hyaluronidase-fihj as part of combination regimens for newly diagnosed, relapsed/refractory (R/R), and transplant-ineligible MM.¹

FDA Approves Ziftomenib for R/R NPM1-Mutated AML

One week later, ziftomenib (Komzifti; Kura Oncology and Kyowa Kirin), an oral, once-daily menin inhibitor, received FDA approval for the treatment of adult patients with R/R acute myeloid leukemia harboring a susceptible NPM1 mutation³; this marks the second menin inhibitor approved for this indication.

The approval was based on positive data from the phase 2 KOMET-001 trial (NCT04067336), which enrolled 112 eligible patients in the open-label, single-arm, multicenter study. The confirmed complete remission (CR) plus CR with partial hematological recovery (CRh) rate was 21.4% (95% CI, 14.2-30.2), with a median duration of CR/CRh of 5 months (95% CI, 1.9-8.1). Additionally, 61% of patients achieved measurable residual disease negativity, suggesting deep molecular remission. Lastly, the median overall survival for all R/R patients was 6.6 months, but patients who achieved a CR/CRh saw a notably extended median OS of 18.4 months.

“The clinical data demonstrate deep and durable responses with a manageable safety profile…” Eunice Wang, MD, of Roswell Park Comprehensive Cancer Center, said in a news release.⁴ “…This approval equips physicians with a new oral therapy to integrate into care and improve outcomes for this vulnerable patient population.”

FDA Approves Sevabertinib for Nonsquamous NSCLC

Soon after, the FDA granted accelerated approval to sevabertinib (Hyrnuo; Bayer) for use in patients with nonsquamous NSCLC whose tumors harbor HER2 (ERBB2) tyrosine kinase domain-activating mutations, marking the therapy’s first approval worldwide.⁵ Patients are advised to take the oral treatment twice daily with food at a 20-mg dose until disease progression or unacceptable toxicity.

The approval was based on findings from the SOHO-01 trial (NCT05099172), which evaluated objective response rate (ORR) and duration of response (DOR) as primary end points. Of the patient population, 70 had received prior systemic therapy and were naïve to HER2-targeted therapies. They had an ORR of 71% (95% CI, 59%-82%), and the median DOR was 9.2 months (95% CI, 6.3-15.0), with 54% experiencing responses lasting at least 6 months.

The study also included 52 patients previously treated with systemic therapy and HER2-targeted agents. This cohort had a lower ORR (38%; 95% CI, 25%-53%) and a shorter median DOR (7.0 months; 95% CI, 6.5-not evaluable). However, a higher proportion (60%) achieved responses lasting at least 6 months.

“…sevabertinib will provide an additional treatment option for previously treated patients with advanced NSCLC harboring a HER2-activating mutation,” Christine Roth, executive vice president of global product strategy and commercialization at Bayer, said in a news release.⁶

FDA Approves Pembrolizumab Plus Enfortumab Vedotin for MIBC

Next, the FDA approved the combination of pembrolizumab (Keytruda) and enfortumab vedotin-ejfv (Padcev) for neoadjuvant and adjuvant treatment of MIBC in adults who are ineligible for cisplatin, offering a new frontline option for a patient population with a historically poor prognosis.⁷

The decision was supported by data from the phase 3 KEYNOTE-905/EV-303 trial (NCT03924895), presented at this year’s European Society for Medical Oncology Congress.⁸ The trial demonstrated that perioperative therapy with enfortumab vedotin plus pembrolizumab (EV + P) significantly improved outcomes compared with surgery alone.⁷

EV + P reduced the risk of disease progression or death by 60%. Median event-free survival was not reached in the combination arm vs 15.7 months in the surgery-only group (HR, 0.40). Median overall survival was also not reached with EV + P, compared with 41.7 months for surgery alone (HR, 0.50), reflecting a 50% reduction in the risk of death after 25 months of follow-up. Lastly, pathological complete response rates were 57.1% with combination therapy vs 8.6% with surgery alone.

These results highlight the growing role of antibody-drug conjugates in first-line cancer treatment, demonstrating their potential to improve survival when integrated into early-stage treatment plans.

FDA Approves Durvalumab With FLOT Chemotherapy for Resectable Gastric and Gastroesophageal Junction Cancer

Lastly, before the Thanksgiving holiday, the FDA approved durvalumab (Imfinzi; AstraZeneca) in combination with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy as a neoadjuvant and adjuvant treatment, followed by single-agent durvalumab, for adults with resectable, early-stage, or locally advanced gastric or gastroesophageal junction adenocarcinoma.⁹ This approval, granted on November 25, is the first perioperative immunotherapy for patients with early gastric and gastroesophageal cancers.

This approval was based on findings from the phase 3 MATTERHORN trial (NCT04592913), which were presented at the 2025 American Society of Clinical Oncology Annual Meeting this past summer.¹⁰ The study randomized patients with resectable GC/GEJC 1:1 to receive either 1500 mg of durvalumab or placebo every 4 weeks plus FLOT for 4 cycles, followed by durvalumab or placebo every 4 weeks for 10 cycles.⁹ The primary end point was event-free survival, with secondary end points of pathological complete response and overall survival.

Two-year event-free survival was 67.4% among the durvalumab group and 58.5% in the placebo group (HR, 0.71; 95% CI, 0.58-0.86; P < .001). Meanwhile, 2-year overall survival was 75.7% in the durvalumab group and 70.4% in the placebo group (HR for months 0-12, 0.99 [95% CI, 0.70-1.39]; HR from month 12 onward, 0.67 [95% CI, 0.50-0.90]; P = .03). Lastly, 19.2% of the durvalumab group had a pathological complete response vs 7.2% in the placebo group (relative risk, 2.69; 95% CI, 1.86-3.90).

“In my opinion, this [approval] immediately makes the FLOT plus durvalumab the new standard of care in this scenario, such that almost every patient, unless there’s a reason not to, ought to be considered for FLOT plus durvalumab in the perioperative management of gastric and gastroesophageal cancer,” Zev A. Wainberg, MD, MATTERHORN trial investigator, said in an interview with The American Journal of Managed Care^® (AJMC).¹¹

References

1. Shaw ML. FDA approves daratumumab and hyaluronidase-fihj for high-risk MM. AJMC. November 6, 2025. Accessed December 12, 2025. https://www.ajmc.com/view/fda-approves-daratumumab-and-hyaluronidase-fihj-for-high-risk-mm
2. Inman S. Daratumumab significantly delays smoldering multiple myeloma progression. AJMC. December 9, 2024. Accessed December 12, 2025. https://www.ajmc.com/view/daratumumab-significantly-delays-smoldering-multiple-myeloma-progression
3. Joszt L. FDA approves ziftomenib for R/R NPM1-mutated AML. November 13, 2025. Accessed December 12, 2025. https://www.ajmc.com/view/fda-approves-ziftomenib-for-r-r-npm1-mutated-aml
4. Kura Oncology and Kyowa Kirin announce FDA approval of Komzifti (ziftomenib), the first and only once-daily targeted therapy for adults with relapsed or refractory NPM1-mutated acute myeloid leukemia. News release. Kura Oncology. November 13, 2025. Accessed November 13, 2025. https://ir.kuraoncology.com/news-releases/news-release-details/kura-oncology-and-kyowa-kirin-announce-fda-approval-komziftitm
5. Bonavitacola J. FDA approves sevabertinib for nonsquamous NSCLC. AJMC. November 19, 2025. Accessed December 12, 2025. https://www.ajmc.com/view/fda-approves-sevabertinib-for-nonsquamous-nsclc
6. US FDA accepts new drug application under priority review for sevabertinib (BAY 2927088) in HER2-mutant non-small cell lung cancer. News release. Bayer. May 28, 2025. Accessed December 12, 2025. https://www.bayer.com/en/us/news-stories/sevabertinib
7. Jeremias S. FDA approves pembrolizumab plus enfortumab vedotin for MIBC. AJMC. November 21, 2025. Accessed December 12, 2025. https://www.ajmc.com/view/fda-approves-pembrolizumab-plus-enfortumab-vedotin-for-mibc
8. Caffrey M. Enfortumab vedotin plus pembro cuts risk of disease progression, death 60% for patients with MIBC who can’t have chemo with bladder removal. AJMC. October 18, 2025. Accessed December 12, 2025. https://www.ajmc.com/view/enfortumab-vedotin-plus-pembro-cuts-risk-of-disease-progression-death-60-for-patients-with-mibc-who-can-t-have-chemo-with-bladder-removal
9. McCormick B. FDA approves durvalumab with FLOT chemotherapy for resectable gastric and gastroesophageal junction cancer. AJMC. November 25, 2025. Accessed December 12, 2025. https://www.ajmc.com/view/fda-approves-durvalumab-with-flot-chemotherapy-for-resectable-gastric-and-gastroesophageal-junction-cancer
10. Caffrey M. adding perioperative durvalumab to chemo combo boosts EFS, overall survival in patients with gastric GEJ cancer. AJMC. June 1, 2025. Accessed December 12, 2025. https://www.ajmc.com/view/adding-perioperative-durvalumab-to-chemo-combo-boosts-efs-overall-survival-in-patients-with-gastric-gej-cancer
11. McCormick B. Experts say FDA approval of perioperative durvalumab plus FLOT sets new standard of care for early-stage gastric, GEJ cancers. AJMC. December 3, 2025. Accessed December 12, 2025. https://www.ajmc.com/view/experts-claim-fda-approval-of-perioperative-durvalumab-plus-flot-establishes-new-standard-for-early-stage-gastric-gej-cancer