FDA Issues Four Oncology/Hematology Approvals in June

  • Two New Indications for Pembrolizumab. The FDA extended the indication of the PD-1 inhibitor pembrolizumab (Keytruda®, Merck) to include its use as a first-line therapy in patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) and for the treatment of patients with metastatic small cell lung cancer (SCLC) who have disease progression after at least two lines of therapy, including a platinum-based chemotherapy.
    • In HNSCC, pembrolizumab was approved for use in all patients, regardless of PD-L1 expression, in combination with platinum and fluorouracil chemotherapy and as a monotherapy for patients whose tumors express PD-L1. The PD-L1 IHC 22C3 pharmaDx kit was approved for use as a companion diagnostic for this indication. This approval was based on results from the phase 3 KEYNOTE-048 trial, where pembrolizumab plus chemotherapy was associated with a significant improvement in overall survival (OS) compared to chemotherapy plus cetuximab (13.0 months vs 10.7 months; HR 0.77, P = .0067) in all patients, regardless of PD-L1 expression status. Pembrolizumab monotherapy also resulted in a significant improvement in OS over cetuximab plus chemotherapy, but only in PD-L1-positive patients.
    • The decision to approve pembrolizumab in SCLC followed pooled results from two multicohort trials, KEYNOTE-158 and KEYNOTE-028, which included 83 patients with SCLC. In these patients with SCLC, pembrolizumab monotherapy resulted in an overall response rate (ORR) of 19%. Responses were durable, with 94% of responding patients remaining in response at 6 months, 63% at 12 months, and 56% at 18 months. The adverse events (AEs) associated with pembrolizumab were manageable and consistent with the known safety profile of this agent.
  • Daratumumab Improves Transplant-Ineligible Multiple Myeloma. The CD38-targeting antibody daratumumab (Darzalex®, Janssen Biotech, Inc) received approval for use in combination with lenalidomide and low-dose dexamethasone (DRd) for newly diagnosed patients with multiple myeloma who are ineligible for autologous stem cell transplant (ASCT). In the randomized phase 3 MAIA trial, DRd resulted in a significant improvement in median progression-free survival (PFS) compared to lenalidomide plus low-dose dexamethasone alone (not reached vs 31.9 months; HR 0.56, P < .0001) in 737 transplant-ineligible patients with newly diagnosed multiple myeloma. Approximately half of patients included in the DRd arm experienced an infusion reaction, a common side effect associated with daratumumab treatment. Patients undergoing daratumumab treatment should receive appropriate prophylaxis and be carefully monitored.
  • Polatuzumab Vedotin, A New Antibody-Drug Conjugate for DLBCL. Polatuzumab vedotin-piiq (Polivy™, Genentech), an antibody-drug conjugate (ADC) combining a CD79b-targeted antibody with a monomethyl auristatin E (MMAE) payload, was approved for use in combination with bendamustine and rituximab (BR) for the treatment of patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL) who have progressed on at least two prior therapies. This approval was based on results from a cohort of 80 patients with relapsed/refractory DLBCL included on the phase 2 study GO29365. In this trial, patients who received polatuzumab vedotin-piiq in combination with BR were more likely to achieve complete response (CR) compared to patients who received BR alone (40% vs 18%). Responses to polatuzumab vedotin-piiq were durable, with 48% of responding patients remaining in response at 12 months. Polatuzumab vedotin-piiq in combination with BR is primarily associated with hematologic AEs, including neutropenia, thrombocytopenia, and anemia. Cytopenias were the most common reason for treatment discontinuation.


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