FDA Approves Adjuvant Nivolumab in Resected Stage IIB or IIC Melanoma

• Adjuvant nivolumab is now an FDA-approved treatment for patients with resected stage IIB or IIC melanoma.

• Findings from the pivotal phase 3 CheckMate-76K clinical trial (NCT04099251) support this regulatory decision.

• Safety findings in CheckMate-76K were consistent with previous reports and were manageable.

The FDA has granted approval to nivolumab (Opdivo) as monotherapy for the adjuvant treatment of patients with resected stage IIB or IIC melanoma, according to Bristol Myers Squibb.¹

The approval is supported by results from the pivotal phase 3 CheckMate-76K clinical trial, which showed a statistically significant and clinically meaningful reduction in risk of recurrence or death in patients with resected stage IIB or IIC melanoma who were treated with adjuvant nivolumab monotherapy compared with those who received placebo.

CheckMate-76K included 790 patients with completed resected disease and a negative sentinel lymph node biopsy. Patients were randomized 2:1 to receive 480 mg every 4 weeks for up to 12 months or matching placebo. The prospective period of treatment was 12 months. Recurrence-free survival (RFS) was the primary end point of the study. The secondary end points explored were overall survival, safety, and distant metastasis-free survival (DMFS). As another secondary end point, the study evaluated investigator-assessed outcomes on next-line therapy including objective response rate, duration of next-line treatment, progression-free survival 2, and end of next-line treatment.

The minimum follow-up in the study was 7.8 months, and median follow-up was 15.8 months in the nivolumab arm and 15.9 months in the placebo arm. The mean duration of treatment was 8.8 months (range, 0-12.1 months) in the nivolumab arm and 9.9 months (range, 0-12.7 months in the placebo arm. Patients were administered a median of 12 doses of therapy (range, 1-14 doses) of nivolumab vs 13 doses (range, 1-14 doses) of placebo.

Adjuvant treatment with nivolumab monotherapy specifically achieved a 58% reduction in the risk of recurrence or death compared with placebo (HR, 0.42; 95% CI, 0.30-0.59; P <.0001). Results for the primary end point of RFS also showed the 12-month RFS rates with nivolumab vs placebo to be 89% (95% CI, 86%-93%) vs 79% (95% CI, 74%-84%), respectively.

Melanoma: © David A Litman - stock.adobe.com

The RFS benefit was carried across all prespecified subgroups, including patients with various T categories and disease stages. Patients with T3b category disease longer RFS compared with placebo (HR, 0.36; 95% CI, 0.19-0.68) as did those with T4a category disease (HR, 0.27; 95% CI, 0.12-0.63), and T4b category disease (HR, 0.52; 95% CI, 0.33-0.82).

Overall, 45 (9%) patients in the nivolumab arm recurred compared with 58 (22%) of the placebo arm. Eleven patients (2%) treated with nivolumab showed new melanoma lesions vs 8 (3%) in the placebo arm. Notably, 10 patients (2%) in the nivolumab vs 3 (1%) in the placebo arm died prior to recurrence.

In terms of DMFS, a clinically meaningful improvement was shown with nivolumab vs placebo (HR, 0.47; 95% CI, 0.30-0.72).

Safety results showed that grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 10% of the nivolumab arm vs 2% of the placebo arm. These TRAEs led to treatment discontinuation in 15% of nivolumab arm compared with 3% of the placebo arm. The most common any-grade AEs shown with nivolumab were rash, diarrhea/colitis, and hepatitis.

The safety findings in CheckMate-76K were consistent with previous reports and were manageable.

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. Bristol Myers Squibb Presents data from CheckMate -76K showing Opdivo (nivolumab) reduced the risk of recurrence or death by 58% versus placebo in patients with completely resected stage IIB or IIC melanoma. News release. Bristol Myers Squibb. October 19, 2022. Accessed May 11, 2023.