Top news of the week in oncology, and cancer drug development.
Pembrolizumab Approved for Head and Neck Cancer
The FDA has granted an accelerated approval to pembrolizumab as a treatment for patients with recurrent or metastatic head and neck squamous cell carcinoma following progression on a platinum-based chemotherapy, based on objective response rates in the phase Ib KEYNOTE-012 study.
The approval was based on an efficacy analysis of 174 patients treated with a prior platinum-based agent. In this assessment, the ORR with pembrolizumab was 16% (95% CI, 11-22), which included a complete response rate of 5%. Responses lasted for ≥6 months for 82% of patients. Pembrolizumab was approved regardless of PD-L1 staining, and at a fixed dose of 200 mg every 3 weeks. In data from the KEYNOTE-012 presented at the 2016 ASCO Annual Meeting for 192 patients, pembrolizumab had an ORR of 18% and a stable disease rate of 17% in patients with recurrent/metastatic HNSCC.
Across the full population, the 6-month PFS rate was 25% and the 12-month rate was 17%. Median OS across evaluable patients was 8.0 months (95% CI, 6-10). At 12 months, 38% of patients remained alive.
Frontline Nivolumab Misses PFS Endpoint in NSCLC
Monotherapy with nivolumab failed to improve progression-free survival compared with physician's choice of combination chemotherapy for patients with PD-L1—positive non–small cell lung cancer, according to topline findings from the phase III CheckMate-026 study. The study enrolled 541 patients with nonsquamous and squamous NSCLC.
All patients enrolled in the study had PD-L1 expression on ≥5% of tumor cells. Full results from the trial are being prepared for presentation at an upcoming medical meeting, according to the company. The topline findings from the study came as a surprise, since nivolumab's main competitor, pembrolizumab, had demonstrated improvements in overall survival and PFS as a frontline monotherapy for patients with high PD-L1—expressing NSCLC, according to topline phase III findings reported in mid-June.
This study, known as the KEYNOTE-024 trial, enrolled 305 patients with both squamous and nonsquamous NSCLC. Patients in KEYNOYE-024 had tumors with ≥50% PD-L1 expression, representing a more selective group. Subsequent subgroup analyses of the CheckMate-026 study will continue to assess subpopulations, including PD-L1. Additionally, OS and ORR will be assessed. Prior phase III studies have shown mixed results for nivolumab for PFS, with many failing to show a benefit for the PD-1 inhibitor versus standard therapies.
A full analysis of the data from CheckMate-026 will be needed before a full conclusion can be drawn.
Pembrolizumab Approved in Europe for Lung Cancer
The European Commission has approved pembrolizumab as a treatment for patients with locally advanced or metastatic PD-L1—positive non–small cell lung cancer following at least 1 chemotherapy regimen. The approval stipulates that patients whose tumors are EGFR or ALK positive should first receive an EFGR or ALK inhibitor, respectively, prior to treatment with pembrolizumab.
The approved dose for the anti—PD-1 agent is 2 mg/kg every 3 weeks. The EC’s decision, which was primarily based on data from the KEYNOTE-0101 trial, follows a previously issued recommendation from the Committee for Medicinal Products for Human Use. Under the approval, pembrolizumab can now be marketed for this indication across 28 European Union member states.
The median OS was 10.4 months with the 2-mg/kg dose of pembrolizumab compared with 8.5 months with docetaxel in those with >1% PD-L1 expressing NSCLC (HR, 0.71; P = .001). In those with ≥50% PD-L1 expression, the median OS with the 2 mg/kg dose of pembrolizumab was 14.9 months versus 8.2 months with docetaxel (HR, 0.54; P = .001).
Ribociclib Given Breakthrough Designation for Breast Cancer
The FDA has granted a breakthrough therapy designation to the CDK4/6 inhibitor ribociclib in combination with letrozole for its potential as a frontline therapy for patients with hormone-receptor-positive, HER2-negative advanced breast cancer. The designation, which is meant to expedite the development of promising new therapies, was based on findings from the phase III MONALEESA-2 trial, in which ribociclib and letrozole significantly improved progression-free survival compared with letrozole alone.
Based on this improvement, the study was halted in May. Data have not yet been released from the study and are being prepared for presentation at an upcoming medical meeting and for regulatory submissions. There are currently several CDK4/6 inhibitors in development, including abemaciclib and palbociclib, which is FDA-approved as a frontline therapy in combination with letrozole and as a second-line therapy with fulvestrant for patients with HR+, HER- advanced breast cancer.
Partial Hold Placed on Pivotal Trial of T-Cell Therapy in Sarcoma
The FDA has placed a partial clinical hold on a planned pivotal trial examining NY-ESO SPEAR (Specific Peptide Enhanced Affinity Receptor) T-cell therapy in patients with myxoid round cell liposarcoma (MRCLS). Adaptimmune reported that the hold is not related to safety issues. In its notification of the hold, the FDA asked Adaptimmune questions related to the trial design and requested additional information on CMC (chemistry, manufacturing, and controls).
The hold will not affect patients, as the study is not yet active and no patients have been recruited. In February 2016, the T-cell therapy received an FDA breakthrough therapy designation for the treatment of patients with inoperable or metastatic pretreated synovial sarcoma who harbor HLA-A*201, HLA-A*205, or HLA-A*206 alleles and whose tumors express the NY-ESO-1 tumor antigen. NY-ESO-1 is highly expressed in the majority of synovial sarcomas and MRCLS.