Bristol-Myers Squibb announced updated results from the CheckMate-012 study illustrating that the combination of the PD-1 inhibitor Opdivo (nivolumab) and the CTLA-4 inhibitor Yervoy (ipilimumab) exhibited efficacy in the treatment of chemotherapy-naïve patients with advanced non-small-cell lung cancer (NSCLC). Results from the Phase Ib trial, which were presented at the American Society of Clinical Oncology (ASCO) annual meeting, showed that the combination regimen was associated with higher confirmed objective response rates (ORR) than Opdivo monotherapy, with the greatest effects observed in patients with increased PD-L1 expression.
In the 412-patient study, Opdivo was administered as monotherapy or as part of a combination with other agents, including Yervoy, at different doses and schedules. The pooled analysis presented at ASCO included data from 129 patients in one of two cohorts comparing the combination of Opdivo plus Yervoy with Opdivo alone. The primary endpoint was safety, while secondary endpoints included ORR and progression-free survival (PFS). Additionally, exploratory endpoints included overall survival and efficacy by PD-L1 expression.
Results demonstrated that confirmed ORR for patients who received Opdivo every two weeks, plus Yervoy either every six weeks or 12 weeks, was 39 percent and 47 percent, respectively, compared with 23 percent for Opdivo monotherapy. When evaluated based on PD-L1 expression, Bristol-Myers Squibb said confirmed ORR in the combination regimen cohorts was 57 percent in patients whose PD-L1 levels were at least 1 percent, and was up to 92 percent among those with levels of 50 percent or more. In patients with less than 1 percent PD-L1 expression, the company said confirmed ORR was 15 percent.
Additionally, median PFS was 4.7 months among patients on the less-frequent Yervoy dosing schedule whose PD-L1 expression was below 1 percent, 8.1 months for those who had PD-L1 levels of 1 percent or more, and 13.6 months for those with PD-L1 levels of at least 50 percent. Bristol-Myers Squibb noted that total adverse event rates were comparable across the combination therapy and monotherapy arms.
Lead researcher Matthew Hellmann remarked that the combination "is both reassuringly safe and manageable while having very compelling efficacy."Hellmann added that the study "provides encouragement that this combination may truly rival if not exceed the benefits that can be achieved with chemotherapy," with further trials under way to test that theory.
Meanwhile, Nick Botwood, Bristol-Myers Squibb's development lead for lung, head and neck cancers, said the results reflect a compelling improvement in the treatment's activity, and are also unprecedented among patients with the highest PD-L1 expressions levels. "We've really been able to show that we have considerably enhanced the tolerability from the earlier regimens we explored," he said. However, Botwood declined to specify when the drugmaker could pursue FDA approval for the combination regimen in the treatment of NSCLC.
In September last year, Bristol-Myers Squibb unveiled results from the Checkmate-012 trial indicating that the combination treatment was associated with ORRs ranging from 13 percent to 39 percent depending on the dosing schedule. The drugmaker had previously announced data from the Phase III CheckMate-067 trial illustrating the effectiveness of the regimen in patients with advanced melanoma.
In October last year, the FDA approved Opdivo in combination with Yervoy for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma. At the time, Bristol-Myers Squibb noted that the move marks the first and only approval of a regimen of two immuno-oncology agents in cancer in the US.
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