FDA Approves Adjuvant Nivolumab for Completely Resected Stage IIB/C Melanoma

FDA

The FDA has approved nivolumab (Opdivo) for the adjuvant treatment of adult and pediatric patients 12 years of age and older with completely resected stage IIB or IIC melanoma.¹

The regulatory decision was supported by data from the phase 3 CheckMate76K trial (NCT04099251), where patients treated with adjuvant nivolumab (n = 526) experienced a 58% reduction the risk of recurrence, new primary melanoma, or death compared with patients treated with placebo (n = 264; HR, 0.42; 95% CI, 0.30-0.59; P < .0001). The 1-year recurrence-free survival (RFS) rates were 89% (95% CI, 86%-92%) for the nivolumab arm vs 79% (95% CI, 74%-84%) for the placebo arm.

“Following surgical removal of melanoma, patients may believe they are free of disease,” 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, stated 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.”

The randomized, double-blind CheckMate76K trial enrolled patients with histologically confirmed, resected, stage IIB or IIC cutaneous melanoma who had not received prior treatment, had a negative sentinel lymph node biopsy, and had an ECOG performance status of 0 or 1.²

Patients were excluded if they had a history of ocular or mucosal melanoma, or active known or suspected autoimmune disease. Prior treatment with an anti–PD-1, anti–PD-L1, anti–PD-L2, anti-CD137, or anti–CTLA-4 therapy, or agents targeting interleukin-2 pathways, T-cell stimulators, or checkpoint pathways, was not permitted.

Patients were randomly assigned 2:1 to receive 480 mg of intravenous nivolumab once every 4 weeks or placebo for up to 1 year or until disease progression or unacceptable toxicity.¹

Investigator-assessed RFS served as the trial's primary end point. Secondary end points included overall survival, distant metastasis–free survival, progression-free survival through next-line therapy, and safety.

Additional data from a prespecified, exploratory subgroup analysis showed that nivolumab elicited 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). In the nivolumab arm, the 1-year RFS rates were 93% (95% CI, 89%–95%) for patients with stage IIB disease and 84% (95% CI, 78%–88%) for those with stage IIC disease. For patients treated with placebo, those rates were 84% (95% CI, 77%–89%) and 72% (95% CI, 62%–80%), respectively.

Regarding safety, 18% of patients treated with nivolumab experienced serious adverse effects (AEs). AEs reactions leading to permanent discontinuation of nivolumab reported in more than 1% of patients consisted of arthralgia (1.7%), rash (1.7%), and diarrhea (1.1%). One patient (0.2%) experienced a fatal AE of heart failure and acute kidney injury.

Grade 3/4 lab abnormalities that occurred in at least 1% of patients treated with nivolumab 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 arm, the most common any-grade AEs were fatigue (36%), musculoskeletal pain (30%), rash (28%) diarrhea (23%) and pruritus (20%).

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