The approval follows 5 months after Bristol-Myers Squibb submitted phase 3 results of the Checkmate-066 trial for FDA review.
The new class of immuno-oncology molecules are definitely keeping up with the promised potential of these agents. Nivolumab, approved yesterday for treating advanced renal cell carcinoma patients who have progressed, the drug was approved today as first line treatment for treating treatment-naïve melanoma patients whose tumors express a wild type (WT) BRaf V600. The approval follows 5 months after Bristol-Myers Squibb submitted phase 3 results of the Checkmate-066 trial for FDA review.
With overall survival (OS) as the primary endpoint, Checkmate-066 evaluated nivolumab as a single agent in treatment-naïve patients with unresectable or metastatic BRaf WT melanoma. Patients received either nivolumab (n = 210; 3 mg/kg intravenously, once every 2 weeks) or dacarbazine (n = 208; 1000 mg/m2, once every 3 weeks). Progression-free survival (PFS) and objective response rate (ORR) were the secondary endpoints.
Interim trial analysis showed a superior OS with nivolumab compared with dacarbazine. Median OS was not reached for nivolumab at the time of analysis; for dacarbazine, it was 10.8 months (95% confidence interval (CI), 9.3-12.1). Nivolumab significantly improved PFS: 5.1 months (95% CI, 3.5-10.8) compared with 2.2 months (95% CI, 2.1-2.4) for patients treated with dacarbazine (Hazard ratio (HR), 0.43; 95% CI, 0.34-0.56; P<.0001), and ORR was 34% (4% complete response rate, 30% partial response rate [95% CI, 28-41]) compared with 9% with dacarbazine (1% complete response rate, 8% partial response rate [95% CI, 5-13]). Nearly 88% of patients had ongoing responses at the time of analysis, about 68% of whom had at least a 6-month response.
Jeffrey S. Weber, MD, PhD, deputy director of the Laura and Isaac Perlmutter Cancer Center at the NYU Langone Medical Center who has been actively involved with Checkmate-066, said, “Advanced melanoma continues to be one of the deadliest and most challenging cancers to treat, and ongoing research in immuno-oncology from clinical trials like CheckMate -066 shows the potential to provide improved overall survival for newly diagnosed patients with BRAF wild-type metastatic melanoma. This important news means that we now have another new option to offer patients with BRAF wild-type metastatic melanoma.”
Grade 3 and 4 adverse events (AE) were observed in 43% of patients treated with nivolumab, the most common being gamma-glutamyltransferase increase and diarrhea. AE resulted in permanent discontinuation of nivolumab treatment in 7% of patients and dose interruption in 26% of patients. Other documented AE included fatigue, musculoskeletal pain, rash, and pruritis.