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

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Georgina V. Long
Michele Del Vecchio
Jeffrey Weber
Christoph Hoeller
Jean-Jacques Grob
Peter Mohr
Stephan Grabbe
Caroline Dutriaux
Vanna Chiarion-Sileni
Jacek Mackiewicz
Piotr Rutkowski
Petr Arenberger
Gaëlle Quéreux
Tarek Meniawy
Paolo A. Ascierto
Piyush Durani
Maurice Lobo
Federico Campigotto
Brian Gastman
John M. Kirkwood


adjuvant nivolumab, resected melanoma, stage IIB/C


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.


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