FDA approves nivolumab for adjuvant treatment of Stage IIB/C melanoma

Regulatory approval: On Oct 13, 2023, the FDA approved nivolumab (Opdivo) for adjuvant treatment of completely resected Stage IIB/C melanoma in patients aged ≥12 years. Approval was supported by the randomized, double-blind CHECKMATE-76K trial (N=790), in which nivolumab reduced the risk of recurrence or death versus placebo (RFS HR 0.42; 95% CI 0.30–0.59; p<0.0001); median RFS was not reached in either arm. Common adverse reactions (≥20%) included fatigue, musculoskeletal pain, rash, diarrhea, and pruritis.

FDA approval (Oct 13, 2023)

The FDA approved nivolumab (Opdivo; Bristol-Myers Squibb) for adjuvant treatment of completely resected Stage IIB/C melanoma in patients aged ≥12 years.

Supporting evidence: CHECKMATE-76K (NCT04099251)

Approval was supported by CHECKMATE-76K, a randomized, double-blind trial enrolling 790 patients with Stage IIB/C melanoma, randomized 2:1 to nivolumab 480 mg IV every 4 weeks vs placebo, for up to 1 year or until recurrence or unacceptable toxicity.

Key eligibility included complete resection with negative margins and a negative sentinel lymph node within 12 weeks, and ECOG 0–1. Exclusions included ocular/uveal or mucosal melanoma, autoimmune disease, systemic corticosteroids (≥10 mg prednisone equivalent) or other immunosuppressants, and prior melanoma therapy other than surgery. Stratification used AJCC 8th edition stage (T3b vs T4a vs T4b).

Efficacy

Primary endpoint: investigator-assessed recurrence-free survival (RFS).

  • Median RFS: not reached in either arm (nivolumab 95% CI 28.5–NR; placebo 95% CI 21.6–NR)
  • RFS HR: 0.42 (95% CI 0.30–0.59); p<0.0001

Safety and dosing (per FDA communication)

Most common adverse reactions (≥20%): fatigue, musculoskeletal pain, rash, diarrhea, pruritis. Recommended dosing:

  • ≥40 kg: 240 mg q2w or 480 mg q4w
  • <40 kg (pediatric): 3 mg/kg q2w or 6 mg/kg q4w Treatment duration: up to 1 year or until disease progression or unacceptable toxicity.

The review used Project Orbis and the RTOR pilot; reviews at other agencies were ongoing at the time of the FDA communication.

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