Nivolumab Improves Survival in Phase III Nonsquamous NSCLC Study

Nivolumab (Opdivo) improved survival versus docetaxel in patients with pretreated nonsquamous non—small cell lung cancer (NSCLC) in the phase III CheckMate-057 trial, according to Bristol-Myers Squibb (BMS), which manufactures the PD-1 inhibitor.

The study was stopped early after an independent monitoring panel determined the primary endpoint of improved overall survival (OS) had been reached. Eligible patients will now be allowed to continue treatment or cross over to the nivolumab arm in an open-label extension of CheckMate-057.

“The results of CheckMate-057 mark the second time Opdivo has demonstrated a survival advantage in lung cancer,” said Michael Giordano, senior vice president, head of development, Oncology, at BMS.

Previously, data from the pivotal phase III CheckMate-017 trial showed that nivolumab improved OS by 41% versus docetaxel in NSCLC patients with squamous cell histology (9.2 vs 6.0 months; HR = 0.59; 95% CI, 0.44-0.79; P = .00025). The most common high-grade toxicities with nivolumab in the study were fatigue, pneumonitis, and diarrhea.

Based on these efficacy and safety data, the FDA-approved nivolumab in March for the treatment of patients with advanced squamous NSCLC who have progressed on or after platinum-based chemotherapy. The drug was initially approved for advanced melanoma in December 2014.

The phase III open-label CheckMate-057 trial involved 582 previously treated patients with advanced or metastatic nonsquamous NSCLC. Participants were randomized to nivolumab at 3 mg/kg intravenously every 2 weeks or docetaxel at 75 mg/m² intravenously every 3 weeks.

Beyond the primary OS endpoint, secondary endpoints for the trial included progression-free survival and objective response rate (ORR). BMS is working with the study researchers on a timetable for publication and presentation of the data.

Phase I results for nivolumab in patients with nonsquamous NSCLC were previously reported at the 2013 World Conference on Lung Cancer. Data were presented for 129 NSCLC patients who received IV nivolumab at 0.1 to 10 mg/kg every-other-week for ≤12 cycles (4 doses/8 week cycle). The participants had a median age of 65 years and good performance status scores, and more than half had received three or more prior therapies. Across all doses of nivolumab, the median OS was 9.9 months, based on Kaplan-Meier estimates.

Sixty-three of the 129 patients were tested for PD-L1 expression by IHC (29 squamous; 34 nonsquamous). In total, 31 of the 63 patients tested positive for PD-L1 expression, without an apparent association between the marker and histology (52% squamous; 47% nonsquamous). For patients with all histology, a clear advantage was seen in patients who tested positive for PD-L1, though PD-L1—negative patients still experienced responses to treatment with nivolumab.

In the entire subpopulation tested, PD-L1—positive patients experienced an ORR of 16.1% (5/31) compared with 12.5% (4/32) in those testing negative. In patients with nonsquamous histology, ORR was 18.8% (3/16) in the positive group compared with 5.6% (1/18) in the negative group.

Beyond nivolumab, another PD-1 inhibitor, Merck’s pembrolizumab (Keytruda), is also advancing rapidly in the lung cancer space. Pembrolizumab has already received the FDA’s Breakthrough Designation status in advanced NSCLC and new data for the drug will be presented this weekend at the 2015 AACR Annual Meeting.

For his part, Giordano is pleased with how his company’s drug is progressing in the lung cancer setting. “Through our Opdivo clinical development program, we seek to bring the potential for long-term survival to a broad range of patients, across lines of therapy and stages of disease,” said Giordano.