Adjuvant Nivolumab Extends RFS in Resected Stage IIB/C Melanoma

In the phase 3 CheckMate-76K study, adjuvant nivolumab administered to patients with stage IIB/C melanoma resulted in prolonged recurrence-free survival compared with placebo.

Adjuvant nivolumab (Opdivo) showed statistically significant and clinically meaningful benefit in recurrence-free survival (RFS) compared with placebo in patients with completely resected stage IIB/C melanoma, according to an announcement by Bristol Myers Squibb.1

With improvement in RFS, the primary end point of the phase 3 CheckMate-76K study (NCT04099251) was met. A full evaluation of the study will be completed, and results will be announced during an upcoming medical meeting.

“Stage IIB/C melanoma patients are at high risk of disease recurrence, with approximately one third of stage IIB and half of stage IIC patients experiencing recurrence within 5 years after surgery. The results of the CheckMate -76K study represent a significant advancement for patients with stage IIB/C melanoma and an extension of our legacy in the treatment of melanoma,” said Gina Fusaro, PhD, development program lead, melanoma, Bristol Myers Squibb, in a press release. “Recurrence represents a life-altering event for people living with cancer. Treating with Opdivo in earlier stages of cancer, when the immune system may be more responsive, has the potential to help prevent recurrence – a critical goal of improving patient outcomes.”

CheckMate-76K is a randomized, double-blind study. It follows a phase 2 study of adjuvant nivolumab in patients with resected stage IIB/IIC melanoma (NCT0340515). According to results from 23 patients in the study published in the Journal of Clinical Oncology, adjuvant nivolumab achieved an 87.8% RFS (90% CI, 64.2%-96.3%) at 2 years, compared with the historical 2-year RFS of 70%.

In terms of safety, there were no nivolumab-related serious adverse events (AEs). Further, only 2% of patients experienced grade 3 AEs. All others AE were grade 1 or 2, including gastrointestinal toxicity (21%), cutaneous AEs (18%), and musculoskeletal, respiratory, and fatigue AEs (10% each).2

In CheckMate-76K, approximately 790 patients with completely resected stage IIB/C melanoma will be enrolled in the study. In addition to RFS, patients will be assessed for the secondary end points of overall survival, the occurrence of AEs, the severity of AEs, distant metastasis-free survival, and investigator-assessed outcomes on next-line therapies.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.

The study will exclude patients who have a history of ocular or mucosal melanoma, are pregnant or nursing women, have active known or suspected autoimmune disease, a known history of allergy or hypersensitivity to study drug components, or were previously treated with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4 antibody, or agents that target IL-2 pathways, T-cell stimulators, or checkpoint pathways.

REFERENCES:

1. Bristol Myers Squibb announces adjuvant treatment with Opdivo (nivolumab) demonstrated statistically significant and clinically meaningful improvement in recurrence-free survival (RFS) in patients with stage IIB/C melanoma in the CheckMate -76K Trial. News release. Bristol Myers Squibb. September 15, 2022. Accessed September 15, 2022. https://bit.ly/3BJagFT

2. Wilson M, Geskin LJ, Carvajal RD, et al. Adjuvant nivolumab in high-risk stage IIb/IIc melanoma patients: Results from investigator initiated clinical trial. J Clin Oncol. 2022;39(15): 9583-9583. doi:10.1200/JCO.2021.39.15_suppl.9583

3. Effectiveness study of nivolumab compared to placebo in prevention of recurrent melanoma after complete resection of stage IIB/C Melanoma (CheckMate76K). ClinicalTrials.gov. Updated September 2, 2022. Accessed September 15, 2022.