Dr Gastman on Exploratory Biomarker Analysis of the Checkmate76K Trial in Stage IIB/C Melanoma

Brian Gastman, MD, surgical director, Melanoma and High-Risk Skin Cancer Program, Department of Plastic Surgery, Cleveland Clinic, discusses results from a biomarkers analysis of patients with stage IIB/C melanoma in the phase 3 CheckMate76K trial (NCT04099251).

CheckMate76K was designed to assess the efficacy of adjuvant nivolumab (Opdivo) vs placebo in patients with no evidence of stage IIB/C disease after standard wide local excision but a high risk of disease recurrence, Gastman begins. Patients were also required to have a negative sentinel lymph node biopsy. According to previously reported data, adjuvant nivolumab successfully prolonged the primary end point of recurrence-free survival (RFS) vs placebo, Gastman reports.

An exploratory analysis of select baseline primary tumor and serum biomarkers was conducted in patients with early-stage melanoma who received a PD-L1 inhibitor, Gastman introduces. The analysis aimed to understand the association between treatment outcomes with adjuvant nivolumab and the presence of individual biomarkers, he explains. These included interferon gamma-related gene expression signature (IFNγ-sig), tumor mutational burden, BRAF mutations, the percentage of intratumoral CD8+ T cells, tumor cell PD-L1 expression, and serum c-reactive protein (CRP) levels. Analyses were performed both within and between each treatment arm.

Analysis of continuous biomarker levels within treatment arms showed that elevated IFNγ-sig, tumor mutational burden, and percentage of CD8+ T cells, as well as low levels of CRP, were associated with improved RFS in the nivolumab arm, Gastman reports.

However, these biomarkers did not correlate with improvement in the placebo arm. Comparison of outcomes between treatment arms showed that nivolumab produced superior RFS benefit vs placebo across all biomarker subgroups. Notably, patients with the above biomarker profile experienced a numerically greater relative benefit with nivolumab vs placebo.

Dichotomized analyses revealed the same trend. Notably, the study did not identify a clear association between RFS and PD-L1 expression.

Disclosures: Dr Gastman reports serving as a consultant or in an advisory role for Castle Biosciences and Quest Imaging; he served on a speaker's bureau for, and has stock or other ownership interests in Castle Biosciences; he received research funding from Alkermes, Instil Bio, Merck, NeoImmuneTech, and Quest Imaging.