On October 13, 2023, the FDA approved a new indication for nivolumab (Opdivo; Bristol-Myers Squibb), a PD-1 inhibitor, for the adjuvant treatment of completely resected stage IIB/C melanoma in patients aged ≥12 years. The FDA granted this application an orphan drug designation.
Nivolumab has been previously approved for the treatment of many cancers, including the adjuvant treatment of melanoma with lymph node involvement or metastatic melanoma in patients who underwent complete resection.
This approval of nivolumab was supported by results of the CheckMate-76K study, a randomized, placebo-controlled, double-blind clinical trial that enrolled 790 patients with stage IIB/C melanoma. Patients were randomized (2:1) to nivolumab 480 mg or to placebo dosed via intravenous infusion every 4 weeks for up to 1 year or until disease recurrence or unacceptable adverse events. The patients in this trial underwent complete resection of the primary melanoma with negative margins and a negative sentinel lymph node within 12 weeks before randomization. Randomization was stratified by T category according to the American Joint Committee on Cancer’s Cancer Staging Manual, 8th Edition (T3b vs T4a vs T4b).
The primary efficacy measure was recurrence-free survival (RFS), which was defined as the investigator-assessed time between randomization and first disease recurrence (local, regional, or distant metastasis), new primary melanoma, or death from any cause, whichever occurred first. The median RFS was not reached in the nivolumab arm (95% confidence interval [CI], 28.5-not reached) or in the placebo arm (95% CI, 21.6-not reached; hazard ratio [HR], 0.42; 95% CI, 0.30-0.59; P≤.0001). At 1 year, the RFS rate was 89% (95% CI, 86-92) in patients who received nivolumab compared with 79% (95% CI, 74-84) in those who received placebo. In a prespecified exploratory subgroup analysis, the RFS unstratified HR was 0.34 (95% CI, 0.20-0.56) in patients with stage IIB melanoma and 0.51 (95% CI, 0.32-0.81) in patients with stage IIC melanoma.
The most common (≥20%) adverse reactions with nivolumab treatment in CheckMate-76K were fatigue, musculoskeletal pain, rash, diarrhea, and pruritus.
The recommended dose of nivolumab for patients weighing ≥40 kg is 240 mg every 2 weeks or 480 mg every 4 weeks until disease progression or unacceptable adverse events for up to 1 year. The recommended dose for pediatric patients weighing <40 kg is 3 mg/kg nivolumab every 2 weeks or 6 mg/kg every 4 weeks until disease progression or unacceptable adverse events for up to 1 year.