Early Promising Results for Olaparib and Pembrolizumab Combination in Tumor-Agnostic Trial

A recent Phase II clinical trial has demonstrated promising preliminary results for a combination therapy involving the PARP inhibitor olaparib and the PD-1 inhibitor pembrolizumab. Conducted at The University of Texas MD Anderson Cancer Center, the study evaluated this combination in a molecularly matched, tumor-agnostic patient population, focusing particularly on individuals with BRCA1/2 mutations. The trial involved 332 patients across 30 different cancer types, categorized into three genetic groups: patients with BRCA1/2 mutations, those with non-BRCA homologous recombination repair (HRR) mutations, and those with homologous recombination deficiency (HRD). Notably, 18 patients exhibited a complete response to the therapy as seen through radiological assessments, with 11 of these responses occurring within the BRCA1/2 mutation subgroup. Responses were observed in multiple tumor types where these therapies are not currently approved, indicating their potential to expand treatment options. Importantly, the safety profile of the combination aligned with known effects of each drug, with no new safety concerns reported. This dataset represents the largest collection of molecularly matched patients treated with this combination, offering insights into identifying predictive biomarkers for exceptional responses. The findings were presented at the AACR Annual Meeting 2025 by Dr. Timothy Yap. Funding was provided by Merck Sharp & Dohme. Researchers emphasize that further analysis may help refine patient selection for this promising therapeutic approach.