Adjuvant therapy with nivolumab versus placebo in patients with resected stage IIB/C melanoma (CheckMate 76K)

Abstract

Patients with resected stage IIB/C melanoma are at high risk of recurrence with outcomes similar to patients with resected stage IIIB disease. Adjuvant NIVO has shown benefit in patients with resected stage III-IV melanoma. The phase 3 CheckMate 76K (NCT04099251) trial compared adjuvant NIVO vs PBO in patients with completely resected stage IIB/C melanoma. Patients aged ≥12 years were stratified by T category and randomized 2:1 to receive NIVO 480 mg or PBO, intravenously Q4W for 12 months. The primary endpoint was recurrence-free survival (RFS); safety was a key secondary endpoint. Overall, 790 patients were randomized to NIVO (526) vs PBO (264); 61% had stage IIB and 39% had stage IIC disease. Minimum follow-up was 8 months (median: 15.8 months NIVO; 15.9 months PBO); 66/526 (13%) vs 69/264 (26%) had a recurrence event. At this interim analysis, CheckMate 76K met the primary endpoint: NIVO significantly reduced the risk of recurrence vs PBO (stratified HR, 0.42; 95% CI, 0.30-0.59; stratified P<0.0001); 12-month RFS rates for NIVO vs PBO were 89% (95% CI, 86-92) vs 79% (74-84); substage rates were 93% vs 84% (IIB) and 84% vs 72% (IIC). RFS benefit was observed across predefined subgroups. For NIVO, 5% of all patients had distant recurrences and 2% regional; for PBO, it was 12% and 8%. Grade 3-4 treatment-related adverse events (TRAEs) for NIVO vs PBO were 10% vs 2%; any-grade TRAEs leading to discontinuation were 15% vs 3%. There was one treatment-related death (0.2%) with NIVO (heart failure and acute kidney injury). Adjuvant NIVO significantly improved RFS vs PBO and decreased the risk of recurrence or death by 58% in patients with resected stage IIB/C melanoma, with efficacy benefit across subgroups. The safety results were similar to the known anti–PD-1 monotherapy profile with no new safety signals. NIVO is an effective adjuvant treatment option with a clinically meaningful benefit in resected stage IIB/C melanoma. Encore presentation from Society of Melanoma Research, September 2022.