Biomarker study of pembrolizumab in patients with advanced rare cancers.
Summary
This phase 2 study investigated the efficacy of pembrolizumab in 154 patients with advanced rare cancers, conditions often lacking established treatment options. The findings demonstrated an objective response rate of 14.8% and a clinical benefit rate of 26.8%. Multi-modal analysis revealed an association between clinical benefit and biomarkers such as high microsatellite instability (MSI-H), high tumor mutation burden (TMB-H), and a PD-L1 combined positive score (CPS) ≥10. The study also highlighted features of the tumor immune microenvironment, such as increased immune infiltration and T cell activation prior to treatment, as potential predictive markers.
Analysis
🔴 CLINIQUE : This prospective, multi-histology phase 2 study evaluates pembrolizumab in rare cancers, an area with limited therapeutic options. It reports an objective response rate of 14.8% and a clinical benefit rate of 26.8%. Biomarkers MSI-H/TMB-H (OR: 13.9, p = 0.0013) and PD-L1 CPS ≥10 (p = 0.0285) are associated with clinical benefit, suggesting their predictive role. However, responses also occur in biomarker-negative tumors, and efficacy varies by histology, indicating the complexity of these cancers. These findings could justify phase 3 trials specific to certain histologies or implementation studies for these biomarkers, with a potential clinical impact in 3-5 years to guide therapeutic decisions. 🟢 BIOMOL : The study employed multi-modal profiling on baseline, on-treatment, and progression samples to characterize the tumor microenvironment. It discovered that clinical benefit is associated with higher pre-treatment immune infiltration and T cell activation, as well as immune cell recruitment during treatment in moderately infiltrated tumors. Multiplex immunofluorescence confirmed higher baseline T cell densities in responders. These findings suggest that tumor immune microenvironment features may serve as predictive markers beyond genomic assays, paving the way for novel immunophenotyping-based biomarkers.