FDA Approves Nivolumab for Completely Resected Stage IIB or Stage IIC Melanoma in Adult, Pediatric Patients

The FDA has granted approval to nivolumab (Opdivo; Bristol Myers Squibb) for the adjuvant treatment of adult and pediatric patients aged 12 years and older with completely resected stage IIB or IIC melanoma.¹

The approval was based on findings from the randomized, double-blind, phase 3 CheckMate76K trial (NCT04099251), in which the administration of adjuvant nivolumab (n = 526) produced a 58% decrease in the risk of disease recurrence, new primary melanoma, or death compared with patients administered placebo (n = 264; HR, 0.42; 95% CI, 0.30-0.59; P < .0001). Further, the 1-year recurrence-free survival (RFS) rate was 89% (95% CI, 86%-92%) in the nivolumab cohort compared with 79% (95% CI, 74%-84%) in the placebo cohort.

“Following surgical removal of melanoma, patients may believe they are free of disease,” said John M. Kirkwood, MD, distinguished professor of medicine at the University of Pittsburgh School of Medicine and co-director of the Melanoma Center at UPMC Hillman Cancer Center, in a news release. “However, within 5 years of diagnosis, one-third of patients with surgically resected stage IIB and nearly one-half of patients with surgically resected IIC melanoma see their cancer return, underscoring the need for additional treatment options that may help reduce the risk of cancer coming back. The significant recurrence-free survival improvement observed with nivolumab in CheckMate76K is an important step forward for these patients.”

CheckMate76K trial enrolled patients with histologically confirmed, resected, stage IIB or IIC cutaneous melanoma who were not previously treated, who had a negative sentinel lymph node biopsy, and an ECOG performance status of 0 or 1.² Exclusion criteria included a history of ocular or mucosal melanoma, or active known or suspected autoimmune disease. Also, patients were excluded if they received prior treatment with an anti–PD-1, anti–PD-L1, anti–PD-L2, anti-CD137, or anti–CTLA-4 therapy, or medication that target interleukin-2 pathways, T-cell stimulators, or checkpoint pathways.

Patients were randomized 2:1 to receive 480 mg of intravenous nivolumab once every 4 weeks or placebo for up to a year or until disease progression or unacceptable toxicity.¹ The trial’s primary endpoint was investigator-assessed RFS, with secondary end points that included overall survival, distant metastasis–free survival, progression-free survival through next-line therapy, and safety.

In a prespecified exploratory subgroup analysis, nivolumab was found to produce an improvement in RFS for patients with stage IIB melanoma (unstratified HR, 0.34; 95% CI, 0.20-0.56) and patients with stage IIC disease (unstratified HR, 0.51; 95% CI, 0.32-0.81). The 1-year RFS rates in the nivolumab cohort were 93% (95% CI, 89%–95%) for those with stage IIB disease and 84% (95% CI, 78%–88%) for those with stage IIC disease compared to the placebo cohort, in which the rates were 84% (95% CI, 77%–89%) and 72% (95% CI, 62%–80%), respectively.

Among those enrolled in the trial, 18% of patients administered nivolumab experienced serious adverse effects (AEs). AEs that led to permanent discontinuation of nivolumab reported in more than 1% of patients included arthralgia (1.7%), rash (1.7%), and diarrhea (1.1%), with 1 patient (0.2%) experiencing a fatal AE of heart failure and acute kidney injury.

Grade 3/4 lab abnormalities occurring in at least 1% of patients in the nivolumab cohort included lipase (2.9%), increased aspartate aminotransferase (2.2%), increased alanine aminotransferase (2.1%), lymphopenia (1.1%), and decreased potassium (1.0%). In the nivolumab cohort, the most common any-grade AEs were fatigue (36%), musculoskeletal pain (30%), rash (28%), diarrhea (23%), and pruritus (20%).

The approved dose of nivolumab for the adjuvant treatment of adult and pediatric patients at least 12 years of age with completely resected stage IIB/C melanoma and who weigh at least 40 kg is 240 mg administered once every 2 weeks or 480 mg administered once every 4 weeks for up to a year, or until disease recurrence or unacceptable toxicity. In those at least 12 years of age who weigh less than 40 kg, the approved dose is 3 mg/kg once every 2 weeks or 6 mg/kg once every 4 weeks for up to 1 year, or until disease recurrence or unacceptable toxicity.

References

1. U.S. Food and Drug Administration approves Opdivo (nivolumab) as adjuvant treatment for eligible patients with completely resected stage IIB or stage IIC melanoma. News release. Bristol Myers Squibb. October 13, 2023. Accessed October 13, 2023. https://news.bms.com/news/details/2023/U.S.-Food-and-Drug-Administration-Approves-Opdivonivolumab-as-Adjuvant-Treatment-for-Eligible-Patients-with-Completely-Resected-Stage-IIB-or-Stage-IIC-Melanoma1/default.aspx
2. Effectiveness study of nivolumab compared to placebo in prevention of recurrent melanoma after complete resection of stage IIB/​C melanoma (CheckMate76K). ClinicalTrials.gov. Updated October 13, 2023. Accessed October 13, 2023. https://clinicaltrials.gov/study/NCT04099251