Bristol-Myers Squibb on Sunday announced results from its final primary analysis of the Phase III CheckMate -026 study evaluating Opdivo (nivolumab) for first-line use in "a broad PD-L1-positive population" of patients with advanced non-small-cell lung cancer (NSCLC). The findings were presented at the European Society for Medical Oncology (ESMO) congress. The company disclosed top-line results in August showing that the trial had failed to meet its primary endpoint of significantly prolonging progression-free survival (PFS) versus chemotherapy in patients whose tumours expressed PD-L1 on at least 5 percent of cells.
"We thought Opdivo could beat chemotherapy, and we have answered the question…for the broad population it is not enough," remarked Fouad Namouni, head of oncology development at Bristol-Myers Squibb.
CheckMate -026 involved 541 patients with advanced squamous or non-squamous NSCLC who had received no prior systemic treatment for advanced disease and whose PD-L1 expression was at least 1 percent. Participants were randomised to receive either Opdivo intravenously every two weeks or an investigator's choice of platinum-based doublet chemotherapy until disease progression, unacceptable toxicity or completion of six cycles. The primary endpoint was PFS as assessed in patients with PD-L1 tumour expression of at least 5 percent.
Bristol-Myers Squibb reported that in patients with at least 5-percent PD-L1 expression, median PFS was 4.2 months with Opdivo and 5.9 months with chemotherapy. Further, overall survival was 14.4 months and 13.2 months for the respective Opdivo and chemotherapy groups, with the company noting that 60 percent of patients in the chemotherapy arm received subsequent Opdivo use after progression, either through crossover or commercial access. Meanwhile, the safety of Opdivo was consistent with the drug's known safety profile in previous studies, the company added.
Nick Botwood, Bristol-Myers Squibb's development lead for lung cancer, suggested imbalances in the trial, where more women and more patients with high PD-L1 levels got chemotherapy, may have skewed the results. "The study was designed to ask a very specific question at the 5-percent expression," Botwood said, adding "it wasn't designed to ask a question at 50 percent" PD-L1 expression, which is considered a high level.
Commenting on the news, Evercore ISI analyst John Scotti stated that the results were "below expectations." However, analyst Sam Fazeli of Bloomberg Intelligence remarked "no one believes that Opdivo is dead in first line," adding that the PD-1 inhibitor is "a drug that has worked in many settings. It's just that [CheckMate -026] had so many aspects that apparently worked against it." Namouni suggested that adding Opdivo to Bristol-Myers Squibb's older immune-based treatment Yervoy (ipilimumab) could potentially be more effective than chemotherapy, but a large study testing that combination is not expected to be completed until 2018.
Meanwhile, Merck & Co. presented positive data  at the ESMO meeting from two trials of its anti-PD-1 therapy Keytruda (pembrolizumab) for the first-line treatment of patients with metastatic NSCLC. The KEYNOTE-024 study included patients whose tumours expressed high levels of PD-L1, while the KEYNOTE-021 trial enrolled participants regardless of their PD-L1 expression. "With the right tactical moves, Merck can turn Keytruda into the broadest offering in lung cancer," commented analyst Tim Anderson of Sanford C. Bernstein & Co.