FDA Accepts sBLA of Nivolumab Monotherapy for Stage IIB/IIC Melanoma

The FDA has accepted the supplemental biologics license application (sBLA) and the European Medicines Agency (EMA) has validated the type II variation marketing authorization application (MAA) for nivolumab (Opdivo) as monotherapy in the adjuvant setting for patients with completely resected stage IIB or IIC melanoma, according to Bristol Myers Squibb.¹

The sBLA and MAA are supported by safety and efficacy findings from the pivotal phase 3 CheckMate-76K trial (NCT04099251) where treatment with nivolumab led to a statistically significant and clinically meaningful benefit in recurrence-free survival (RFS) compared with placebo in patients with completely resected stage IIB or IIC melanoma.

Additionally, the safety profile of nivolumab alone was consistent with what has previously been reported in studies.²

“Melanoma can be a devastating diagnosis, and patients with stage IIB or IIC melanoma tend to be at high risk of disease recurrence. Approximately one third of stage IIB and half of stage IIC patients experience recurrence within five years after surgery,” said Gina Fusaro, PhD, vice president, development program lead, Bristol Myers Squibb, in the press release. “The data from the CheckMate-76K trial demonstrate the benefit that nivolumab can have for patients with this earlier stage of cancer. We look forward to working with the U.S. Food and Drug Administration and the European Medicines Agency to potentially offer a treatment option to patients with stage IIB or IIC melanoma that could help prevent recurrence.”

The CheckMate-76K is a randomized double-blind, phase 3 study evaluating adjuvant nivolumab in approximately 790 patients with completely resected stage IIB/C melanoma at a dose of 480 mg 4 times a day for up to 12 months vs placebo.³

To be eligible for inclusion, all patients are required to have a negative sentinel lymph node biopsy, be previously untreated, have an ECOG performance status of 0 or 1, and have been diagnosed with histologically confirmed, resected stage IIB/C cutaneous melanoma.

Investigators are assessing the primary end point of RFS and secondary end points of overall survival, distant metastasis-free survival, progression-free survival on next-line therapy, and safety.

Previously in October 2022, results from CheckMate-76K presented at the 2022 Society for Melanoma Research Annual Meetings showed that treatment with adjuvant nivolumab achieved a 58% reduction in the risk of recurrence or death vs placebo in this patient population (HR, 0.42; 95% CI, 0.30-0.59; P <.0001). The RFS rates at 12 months were 89% (95% CI, 86%-92%) in the nivolumab arm vs 79% (95% CI, 74%-84%) in the placebo arm.^1,2

This RFS benefit was carried across the predefined subgroups in the study, including T category and disease stage. For patients with stage IIB melanoma, the 12-month RFS rate was 93% when treated with nivolumab vs 84% with placebo. Patients with stage IIC melanoma given nivolumab had a 12-month RFS rate of 84% compared with 72% in the placebo arm.

Moreover, safety data from CheckMate-76 revealed that 10% of patients experienced grade 3 and 4 treatment-related adverse events (TRAEs) in the nivolumab arm vs 2% in the placebo arm. TRAEs that led to treatment discontinuation were observed in 15% of patients in the nivolumab arm vs 3% of the placebo arm.

In the United States, the assigned Prescription Drug User Fee Act date for nivolumab in this indication is October 13, 2023. The EMA’s validation of the application for nivolumab monotherapy confirms the submission is complete and the centralized review process will begin in Europe.

REFERENCES:

U.S. Food and Drug Administration accepts Bristol Myers Squibb’s supplemental biologics license application and European Medicines Agency validates application for opdivo (nivolumab) …. News release. Bristol Myers Squibb. February 28, 2023. Accessed February 28, 2023.

Bristol Myers Squibb presents data from CheckMate76K 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 February 28, 2023. https://bit.ly/3MSOjIt

Effectiveness study of nivolumab compared to placebo in prevention of recurrent melanoma after complete resection of stage IIB/C melanoma (CheckMate76K). ClinicalTrials.gov. Updated January 13, 2023. Accessed February 28, 2023. https://clinicaltrials.gov/ct2/show/NCT04099251?term=CheckMate-76K&draw=2&rank=1