In October and November, the US FDA approved seven new indications for cancer management. This includes a new dosing regimen for an existing therapy.

• Mirvetuximab Soravtansine-gynx for Folate Receptor Alpha (FRα)-Positive, Platinum-Resistant Ovarian, Fallopian Tube, or Peritoneal Cancer. Accelerated approval was granted to the FRα-directed antibody and microtubule inhibitor conjugate mirvetuximab soravtansine-gynx (Elahere™, ImmunoGen, Inc.) for adult patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens. In addition, approval was granted for an immunohistochemistry-based companion diagnostic assay for detecting the FR1 protein (Ventana FOLR1 [FOLR1-2.1]; Ventana Medical Systems, Inc.). The approval of mirvetuximab was based on efficacy results from the single-arm SORAYA trial, also known as Study 0417, which enrolled 106 previously treated patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. All patients had received bevacizumab. The overall response rate (ORR) was 31.7% and the median duration of response (DoR) was 6.9 months. The recommended mirvetuximab soravtansine-gynx dose is 6 mg/kg, adjusted ideal body weight, once every 3 weeks as an intravenous (IV) infusion until disease progression or unacceptable toxicity. Product labeling includes a boxed warning for ocular toxicity.

• Tremelimumab + Durvalumab for Unresectable HCC. Tremelimumab (Imjudo®, AstraZeneca Pharmaceuticals) in combination with durvalumab (Imfinzi®, AstraZeneca Pharmaceuticals) received approval for patients with unresectable hepatocellular carcinoma (uHCC). Approval was based on efficacy data from the randomized, open-label, multicenter HIMALAYA trial in patients with confirmed uHCC who had not received prior systemic treatment. Patients were randomized to one of three arms: tremelimumab 300 mg as a one-time single IV infusion plus durvalumab 1500 mg IV on the same day, followed by durvalumab 1500 mg IV every 4 weeks; durvalumab 1500 mg IV every 4 weeks; or sorafenib 400 mg orally twice daily until disease progression or unacceptable toxicity. The approval was based on a comparison of patients randomized to tremelimumab plus durvalumab (n=393) or sorafenib (n=389). Tremelimumab plus durvalumab demonstrated a significant and clinically meaningful improvement in overall survival (OS) compared with sorafenib (hazard ratio [HR], 0.78; P = 0.0035); median OS was 16.4 vs. 13.8 months. Median progression-free survival (PFS) was 3.8 vs. 4.1 months for the tremelimumab plus durvalumab and sorafenib arms, respectively (HR, 0.90). ORR was 20.1% in the tremelimumab plus durvalumab arm and 5.1% for those treated with sorafenib.

• Combination of Tremelimumab, Durvalumab, and Chemotherapy for Metastatic NSCLC. Approval was also granted to tremelimumab (Imjudo®, AstraZeneca Pharmaceuticals) in combination with durvalumab (Imfinzi®, AstraZeneca Pharmaceuticals) and platinum-based chemotherapy for patients with metastatic non-small cell lung cancer (NSCLC) with no sensitizing EGFR mutation or ALK genomic tumor aberrations. Efficacy was evaluated in the randomized, phase III, three-arm, active-controlled, open-label POSEIDON trial in treatment- naïve patients with metastatic NSCLC. Patients were randomized to one of three treatment arms: (1) tremelimumab, durvalumab, and platinum-based chemotherapy for 4 cycles, followed by durvalumab and maintenance chemotherapy every 4 weeks; (2) durvalumab plus platinum-based chemotherapy for 4 cycles followed by durvalumab and maintenance chemotherapy; or (3) platinum-based chemotherapy for 6 cycles followed by maintenance chemotherapy. This approval was based on a comparison of treatment arms 1 and 3, which included 675 patients. Tremelimumab plus durvalumab and platinum-based chemotherapy demonstrated a significant and clinically meaningful improvement in OS compared with platinum-based chemotherapy (HR, 0.77; P = 0.00304): median OS was 14 and 11.7 months in the treatment arms 1 and 3, respectively; median PFS was 6.2 and 4.8 months, respectively (HR, 0.72; P = 0.00031).

• Cemiplimab-rwlc for Advanced NSCLC. The FDA approved anti-PD-1 antibody cemiplimab-rwlc (Libtayo®, Regeneron Pharmaceuticals, Inc.) in combination with platinum-based chemotherapy for patients with advanced NSCLC with no EGFR, ALK, or ROS1 aberrations. The results from the global, double-blind, placebo-controlled phase III EMPOWER-Lung3 trial in 466 patients with advanced NSCLC who had not received prior systemic treatment, were used to evaluate efficacy. Patients received either cemiplimab-rwlc (n=312) or placebo (n=154) every 3 weeks in combination with four cycles of physician’s choice platinum-based chemotherapy. Cemiplimab-based therapy resulted in a significant improvement in median OS compared with placebo (21.9 vs. 13.0 months; HR, 0.71; P = 0.014). Median PFS was 8.2 months in the cemiplimab group vs. 5.0 months in the placebo group (HR, 0.56; P < 0.0001). Confirmed ORR was 43.3% and 22.7% in the respective treatment groups.

• New Asparaginase Erwinia Chrysanthemi Dosing. Asparaginase erwinia chrysanthemi (recombinant)-rywn (Rylaze™, Jazz Pharmaceuticals) has been approved for a new Monday-Wednesday-Friday dosing regimen, which includes 25 mg/m² intramuscularly on Monday and Wednesday mornings, and 50 mg/m² intramuscularly on Friday afternoon. In June 2021, the FDA approved asparaginase erwinia chrysanthemi as a component of a multi-agent chemotherapeutic regimen for acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adult and pediatric patients 1 month or older who have developed hypersensitivity to E. coli-derived asparaginase; the recommended dose was 25 mg/m² administered intramuscularly every 48 hours. The new dosing regimen was approved based on the pharmacokinetic analysis of 225 patients in the open-label, multicenter JZP458-201 trial, in which asparaginase erwinia chrysanthemi was administered by various routes and different dosages, and the results were used to develop a model to predict serum asparaginase activity at certain timepoints. Efficacy was determined based on a demonstration of the achievement and maintenance of nadir serum asparaginase activity above the level of 0.1 U/mL by simulation in a virtual population.

• Teclistamab for Relapsed/Refractory (R/R) Multiple Myeloma. Accelerated approval was granted to teclistamab-cqyv (Tecvayli®, Janssen Biotech, Inc.) for patients with R/R multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. Teclistamab-cqyv is the first T cell-redirecting bispecific antibody that targets both CD3 expressed on the surface of T cells and B-cell maturation antigen (BCMA) expressed on myeloma cells. The accelerated approval was based on the single-arm, multi-cohort, open-label, multicenter, phase I–II MajesTEC-1 study. The efficacy population included 110 patients with R/R multiple myeloma who had previously received at least three prior therapies and had not received prior BCMA-targeted therapy. ORR (primary endpoint) based on the International Myeloma Working Group 2016 criteria was 61.8%. With a median follow-up of 7.4 months among responders, the estimated DoR rate was 90.6% at 6 months and 66.5% at 9 months. Teclistamab-cqyv has a boxed warning for life-threatening or fatal cytokine-release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity (ICANS). Teclistamab-cqyv is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), called the Tecvayli REMS.

• Brentuximab Vedotin + Chemo for Pediatric Hodgkin Lymphoma. Approval was granted to the CD30-directed antibody-drug conjugate, brentuximab vedotin (Adcetris®, Seagen, Inc.) in combination with AVE-PC chemotherapy (doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide) for pediatric patients aged ≥2 years old with previously untreated high-risk classical Hodgkin lymphoma. This is the first pediatric approval for brentuximab vedotin. Efficacy was evaluated in the randomized, multicenter, open-label, phase III AHOD1331 trial, which included 600 patients aged 2 – 21 years old with previously untreated high-risk Hodgkin’s lymphoma. High risk was defined as Ann Arbor Stage IIB with bulky disease, Stage IIIB, Stage IVA, and Stage IVB. Patients were assigned to receive 5 cycles of either brentuximab vedotin plus AVE-PC or standard pediatric regimen ABVE-PC (doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide). The main efficacy outcome measure was event-free survival (EFS). Median EFS was not reached with either therapy. Relapse rate was 8% in the brentuximab vedotin group and 17% in the ABVE-PC group. At a median follow up of 43.1 months, the 3-year EFS was 92.1% in the brentuximab vedotin group and 82.5% in the standard chemotherapy group (HR, 0.41; P = 0.0002).