Nivolumab Immunotherapy Receives FDA Approval for Stage IIB-C Melanoma

For completely resected stage IIB and stage IIC melanoma , as adjuvant treatment (to reduce the risk of recurrence after surgery), nivolumab (Opdivo, Bristol-Myers Squibb) immunotherapy received FDA (US Food and Drug Administration) approval on October 13, 2023.

This development represents another approval for these patients' adjuvant treatment—the second FDA approval. Pembrolizumab (Keytruda), for the same indication, was approved by the FDA in 2021.

FDA Approval Based on the CHECKMATE-76K Study

Nivolumab's efficacy in stages IIB and IIC was evaluated in CHECKMATE-76K (NCT04099251), a randomized, double-blind clinical trial.

The study enrolled 790 patients with stage IIB/C melanoma.

Patients were randomized 2:1 to receive intravenous nivolumab 480 mg every 4 weeks or placebo until disease recurrence, unacceptable toxicity, or a maximum of 1 year.

Enrollment required complete excision of the primary melanoma, negative surgical margins, and a negative sentinel lymph node within the preceding 12 weeks. Patients also needed an ECOG performance status of 0 or 1.

Patients with ocular/uveal or mucosal melanoma, autoimmune disease, a need for systemic corticosteroids or other immunosuppressive drugs, or previous melanoma treatment other than surgery were excluded.

Results

The main efficacy outcome was recurrence-free survival, defined as the time to the first event: disease recurrence (local, regional, or distant metastasis), a new primary melanoma, or death from any cause.

Median recurrence-free survival was not reached in either the nivolumab arm (95% CI: 28.5, not reached) or the placebo arm (95% CI: 21.6, not reached). However, nivolumab reduced the risk of cancer recurrence or death by 58% (hazard ratio=0.42 [95% CI: 0.30, 0.59]; p-value=<0.0001).

Most Common Adverse Effects

The most common adverse effects (in 20% or more of patients) were fatigue, musculoskeletal pain, rash, diarrhea, and itching.

Recommended Dosage

For patients weighing 40 kg or more, the recommended nivolumab dose is 240 mg every 2 weeks or 480 mg every 4 weeks until disease progression or unacceptable toxicity. For pediatric patients weighing less than 40 kg, the recommended dose is 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks until disease progression or unacceptable toxicity.

International Collaboration and Review

This review was conducted under Project Orbis, an FDA Oncology Center initiative providing a framework for concurrent submission and review of oncology drugs among international partners. The FDA collaborated with Australia's Therapeutic Goods Administration (TGA), Health Canada, Israel's Ministry of Health (IMoH), and Switzerland's Swissmedic. Reviews by other regulatory agencies are ongoing.

Comparing Opdivo and Keytruda in Adjuvant Treatment of Stage IIB and IIC Melanoma

 Efficacy rates:

• Nivolumab was approved based on CHECKMATE-76K and reduced recurrence risk by 58% .
• Pembrolizumab was approved based on KEYNOTE-716 and reduced recurrence risk by 35% .