Bristol-Myers Squibb Company, a global pharmaceutical company, announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending that nivolumab, a PD-1 immune checkpoint inhibitor, be granted approval for the treatment of locally advanced or metastatic squamous non-small cell lung cancer (NSCLC) after prior chemotherapy in adults. The CHMP positive opinion will now be reviewed by the European Commission, which has the authority to approve medicines for the European Union (EU).
“We are moving at a ground-breaking pace to deliver on a mission that looks to transform cancer treatment options for patients,” said Michael Giordano, senior vice president, head of development, oncology. “Last month, we received a CHMP positive opinion for nivolumab for the treatment of advanced melanoma. Today’s announcement of a positive opinion for nivolumab in NSCLC brings us closer to delivering on our promise of changing the standard of care for lung cancer.”
The CHMP positive opinion is based on data from CheckMate -017 and CheckMate -063, two trials that demonstrated the efficacy and safety of nivolumab in patients with advanced or metastatic squamous NSCLC who had progressed following previous chemotherapy treatment. CheckMate -017 was a Phase III, randomized, open-label trial that included patients who had experienced disease progression during or after one prior platinum doublet-based chemotherapy regimen.
Results from a prespecified interim analysis of CheckMate -017, demonstrated significantly superior overall survival (OS) with nivolumab vs. docetaxel, with a 41% reduction in the risk of death (hazard ratio: 0.59 [95% CI: 0.44, 0.79; p=0.00025]). This benefit was observed regardless of PD-L1 expression status. The estimated one-year survival rate was nearly doubled with nivolumab (42% [95% CI: 34, 50]) compared to docetaxel (24% [95% CI: 17, 31]). The median OS was 9.2 months in the nivolumab arm (95% CI: 7.3, 13.3) and 6 months in the docetaxel arm (95% CI: 5.1, 7.3).
A second study, CheckMate -063, was a phase II single-arm, multinational, multicenter trial that included patients with metastatic squamous NSCLC who had progressed after receiving a platinum-based therapy and at least one additional systemic treatment regimen (65% of patients had received = 3 prior therapies). In CheckMate -063, confirmed objective response rate, the study’s primary endpoint, was 14.5% (17/117) (95% CI = 8.7, 22.2) with an estimated one-year survival rate of 40.8% (95% CI: 31.6, 49.7) and median overall survival of 8.2 months (95% CI: 6.1, 10.9).
In both CheckMate -017 and -063, there was consistent nivolumab dosing of 3 mg/kg every two weeks. The safety profile of nivolumab has been evaluated in thousands of patients enrolled in the broader clinical program and treatment-related adverse events (AEs) were generally managed using established safety algorithms. In CheckMate -017, the safety profile of nivolumab was consistent with prior studies and favorable versus docetaxel. Treatment-related adverse events occurred less frequently with nivolumab than docetaxel (grade 3–4, 6.9% vs. 55%, respectively).
Bristol-Myers Squibb has a broad, global development program to study nivolumab in multiple tumor types consisting of more than 50 trials – as monotherapy or in combination with other therapies – in which more than 8,000 patients have been enrolled worldwide.
Nivolumab became the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world on July 4, 2014 when Ono Pharmaceutical Co. announced that it received manufacturing and marketing approval in Japan for the treatment of patients with unresectable melanoma. In the US, the US Food and Drug Administration (FDA) granted its first approval for nivolumab for the treatment of patients with unresectable or metastatic melanoma and disease progression following Yervoy (ipilimumab) and, if BRAF V600 mutation positive, a BRAF inhibitor. On March 4, 2015, nivolumab received its second FDA approval for the treatment of patients with metastatic squamous non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy.
In addition, nivolumab is being investigated in patients with advanced non-squamous NSCLC. On April 17, 2015, an open-label, randomized Phase III study (CheckMate -057) evaluating nivolumab versus docetaxel in previously treated patients with advanced non-squamous NSCLC was stopped early because an assessment conducted by the independent Data Monitoring Committee (DMC) concluded that the study met its endpoint, demonstrating superior overall survival in patients receiving nivolumab compared to docetaxel. The company plans to share these data with health authorities.