What Oncology Therapies Were Approved by the FDA in November?

This November was accompanied by a slew of FDA approvals across tumor types including multiple hematologic and lung cancers, along with an approval each in genitourinary and gastrointestinal cancers.

Notably, subcutaneous daratumumab became the first FDA-approved treatment for smoldering multiple myeloma on November 6. Further, therapies were given the OK in non-small and small cell lung cancers.

The FDA’s actions in oncology last month included 6 standard approvals, 2 conversions of accelerated approvals to standard ones, and the approval of a pertuzumab biosimilar across all approved indications for the reference drug.

Subcutaneous Daratumumab in High-Risk Smoldering Myeloma

The FDA approved subcutaneous daratumumab and hyaluronidase-fihj (Darzalex Faspro) for use in patients with high-risk smoldering multiple myeloma, marking the first approved agent in smoldering multiple myeloma.¹

The monoclonal antibody’s approval is based on findings from the randomized, open-label phase 3 data from the AQUILA trial (NCT03301220). Median progression-free survival (PFS), the primary end point of the trial, was not evaluable in the subcutaneous daratumumab arm vs 41.5 months in the active monitoring arm (HR, 0.49; 95% CI, 0.36-0.67; P < .0001).

Ziftomenib in NPM1+ Relapsed/Refractory Acute Myeloid Leukemia

The FDA granted approval to the menin inhibitor ziftomenib (Komzifti) for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) harboring NPM1 mutations with no appropriate alternative treatment options.²

According to results from the phase 2 open-label, single-arm, multicenter KOMET-001 trial (NCT04067336), upon which this approval is based³, the rate of complete remission (CR) plus CR with partial hematologic recovery (CRh; CR+CRh) was 21.4% (95% CI, 14.2-30.2; P = .0058)⁴, and the duration of CR+CRh was 5 months (95% CI, 1.9-8.1). The median follow-up was 4.2 months (range, 0.1-41.2). Additionally, the CR rate was 17.0% (95% CI, 10.5-25.2) with a CRh rate of 4.5% (95% CI, 1.5-10.1).

Epcoritamab Plus Lenalidomide/Rituximab in Relapsed/Refractory Follicular Lymphoma

The FDA approved epcoritamab-bysp (Epkinly) with lenalidomide (Revlimid) and rituximab (Rituxan; together R2) for the treatment of relapsed or refractory follicular lymphoma (FL).⁵ With this approval, the FDA has also approved epcoritamab as monotherapy for relapsed or refractory FL following 2 or more lines of systemic therapy, a setting in which the bispecific T-cell engager (BiTE) antibody was granted accelerated approval in June 2024.

The agent’s approval with lenalidomide and rituximab was supported by data from the randomized, open-label phase 3 EPCORE FL-1 trial (NCT05409066), in which 488 patients with relapsed or refractory FL were randomly assigned 1:1 to receive either epcoritamab with R2 or R2 alone.

The addition of epcoritamab reduced the risk of death or disease progression by 79% (HR, 0.21; 95% CI, 0.13-0.33); P < .0001), and the median PFS was not reached (95% CI, 21.9-NR) vs 11.2 months (95% CI, 10.5-NR) in the R2 arm. The overall response rate was 89% (95% CI, 84%-93%) in the epcoritamab arm and 74% in the control arm.

Sevabertinib in HER2+ Nonsquamous Non-Small Cell Lung Cancer

The FDA granted accelerated approval to sevabertinib (Hyrnuo) for the treatment of patients with locally advanced or metastatic, nonsquamous non-small cell lung cancer (NS-NSCLC) with HER2 tyrosine kinase domain (TKD-activating mutations identified by an FDA-approved test who have received prior systemic therapy.⁶

The efficacy of sevabertinib in this patient population was assessed in the open-label, single-arm, multicenter, multi-cohort phase 1/2 SOHO-01 trial (NCT05099172), where it was observed that patients with this disease profile who were HER-targeting treatment-naive who received with sevabertinib (N = 70) had a confirmed objective response rate of 71% (95% CI, 69%-82%).

Tarlatamab in Extensive-Stage Small Cell Lung Cancer

The FDA converted its 2024 accelerated approval of tarlatamab-dlle (Imdelltra) for the treatment of adults with extensive-stage small cell lung cancer (ES-SCLC) with disease progression during or after platinum-based chemotherapy to a standard one.⁷

The efficacy of tarlatamab in this patient population was evaluated in the multicenter, randomized, open-label phase 3 DeLLphi-304 (NCT05740566). Tarlatamab was shown to reduce the risk of death by 40%, with patients in this patient population who received tarlatamab having a median OS of 13.6 months (95% CI, 11.1-not evaluable [NE]) vs 8.3 months (95% CI, 7.0-10.2) in the standard-of-care (SOC) arm (HR, 0.60; 95% CI, 0.47-0.77; P < .001).

Further, tarlatamab reduced the risk of disease progression or death by 38%, with a median PFS of 4.2 months (95% CI, 3.0-4.4) in the tarlatamab arm compared with 3.2 months (95% CI, 2.9-4.2) in the SOC arm (HR, 0.72; 95% CI, 0.59-0.88; P < .001).

Neo/Adjuvant Pembrolizumab Plus Enfortumab in Muscle-Invasive Bladder Cancer

The FDA approved intravenous (IV) pembrolizumab (Keytruda) or subcutaneous pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex) with enfortumab vedotin-ejfv (Padcev) for neoadjuvant treatment followed by adjuvant treatment preceded by cystectomy in adult patients with muscle-invasive bladder cancer (MIBC) who are not eligible for cisplatin chemotherapy.⁸

The approval is supported by data from the open-label, randomized, multicenter, active-controlled phase 3 KEYNOTE-905/EV-303 trial (NCT03924895). Median event-free survival was not reached (NR) for patients in the experimental arm (95% CI, 37.3-NR) vs 15.7 months (95% CI, 10.0-20.5) in the control arm (HR, 0.40; 95% CI, 0.28-0.57; P < .0001).

Further, the combination resulted in a 50% reduction in the risk of disease progression or death. Median OS was NR (95% CI, NR-NR) in the experimental arm compared with 41.7 months (95% CI, 31.8-NR) in the surgery-alone arm (HR, 0.50; 95% CI, 0.33-0.74; P = .0002).

Neo/Adjuvant Durvalumab Plus Chemotherapy in Gastric/GEJ Adenocarcinoma

The FDA approved the combination of durvalumab (Imfinzi) plus FLOT chemotherapy (fluorouracil, leucovorin, oxaliplatin, and docetaxel) followed by durvalumab monotherapy for the neoadjuvant and adjuvant treatment of patients with resectable gastric or gastroesophageal junction adenocarcinoma (GC/GEJ).⁹

The safety and efficacy of durvalumab in this setting was evaluated in the randomized, double-blind, placebo-controlled, multicenter phase 3 MATTERHORN trial (NCT04592913). Median event-free survival, the primary efficacy outcome measured, was not reached (95% CI, 40.7 months-NE) in the durvalumab arm compared with 32.8 months (95% CI, 27.9-NE) in the placebo arm (HR, 0.71; 95% CI, 0.58-0.86; P < .001). Median OS, an additional efficacy outcome measured, was not reached in either arm (HR, 0.78; 95% CI, 0.63-0.96; P = .021).

References

1. FDA approves revumenib for relapsed or refractory acute myeloid leukemia with a susceptible NPM1 mutation. FDA. October 24, 2025. Accessed October 24, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-revumenib-relapsed-or-refractory-acute-myeloid-leukemia-susceptible-npm1-mutation
2. FDA approves ziftomenib for relapsed or refractory acute myeloid leukemia with a NPM1 mutation. FDA. November 13, 2025. Accessed November 13, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ziftomenib-relapsed-or-refractory-acute-myeloid-leukemia-npm1-mutation
3. Kura Oncology and Kyowa Kirin announce publication of pivotal ziftomenib data in relapsed/refractory NPM1-mutated AML in the Journal of Clinical Oncology. Kura Oncology, Inc. September 25, 2025. Accessed November 13, 2025. https://ir.kuraoncology.com/news-releases/news-release-details/kura-oncology-and-kyowa-kirin-announce-publication-pivotal
4. Wang ES, Montesinos P, Foran J, et al. Ziftomenib in relapsed or refractory NPM1-mutated AML. J Clin Oncol. 2025;43(31):3381-3390. doi:10.1200/JCO-25-01694
5. FDA approves epcoritamab-bysp for follicular lymphoma indications. FDA. November 18, 2025. Accessed November 18, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-epcoritamab-bysp-follicular-lymphoma-indications
6. FDA grants accelerated approval to sevabertinib for non-squamous non-small cell lung cancer. FDA. November 19, 2025. Accessed November 19, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sevabertinib-non-squamous-non-small-cell-lung-cancer
7. FDA grants traditional approval to tarlatamab-dlle for extensive stage small cell lung cancer. News release. FDA. November 19, 2025. Accessed November 19, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-traditional-approval-tarlatamab-dlle-extensive-stage-small-cell-lung-cancer
8. FDA approves pembrolizumab with enfortumab vedotin-ejfv for muscle invasive bladder cancer. FDA. November 21, 2025. Accessed November 21, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-enfortumab-vedotin-ejfv-muscle-invasive-bladder-cancer
9. FDA approves durvalumab for resectable gastric or gastroesophageal junction adenocarcinoma. FDA. November 25, 2025. Accessed November 25, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-resectable-gastric-or-gastroesophageal-junction-adenocarcinoma