Randomized phase II trial of olaparib and pembrolizumab vs olaparib alone as maintenance therapy in metastatic pancreatic cancer patients with germline BRCA1 or BRCA2 (gBRCA1/2) mutations: SWOG S2001.

作者：Vincent Chung, Katherine A. Guthrie, Michael J. Pishvaian, Andrew M. Lowy, Davendra Sohal, Sarah Colby, Kim Anna Reiss, Gazala Khan, Rafael Winograd, Jeffrey A. Meyerhardt, Eileen M. O'Reilly, E. Gabriela Chiorean, Philip Agop Philip · 发表于：Journal of Clinical Oncology · 年份：2026 · DOI：10.1200/jco.2026.44.16_suppl.4012 · 被引用次数：1 · 研究领域：PARP inhibition in cancer therapy、Lung Cancer Research Studies、Cancer Immunotherapy and Biomarkers

4012 Background: Preclinical studies have demonstrated that PARP inhibitors modulate the immune microenvironment by increasing genomic instability, PD-L1 expression and activating the immune inflammatory stimulator of interferon genes (STING) pathway. The POLAR trial demonstrated promising results combining pembrolizumab with olaparib as maintenance therapy in patients (pts) with homologous recombination deficiency (HRD) mutations. S2001 is a randomized phase II trial evaluating the addition of pembrolizumab to olaparib as maintenance therapy in patients with gBRCA1/2. Methods: Eligible pts had mPDA with gBRCA1/2 mutations and had received a minimum of 4 months of platinum-based chemotherapy without progression. Pts were randomized 1:1 to olaparib 300 mg twice per day plus pembrolizumab 200 mg every 3 weeks or olaparib alone. The primary endpoint was progression-free survival (PFS) with a target hazard ratio (HR) of 0.6 (median PFS 7.0 vs 11.7 months) with 1-sided alpha=0.1 and 80% power. Secondary outcomes were safety and tolerability, overall survival (OS), overall response rate (ORR), and disease control rate (DCR). The accrual goal was 88 pts to have 78 eligible for analysis. Differences in PFS by treatment arm were assessed via stratified log-rank test, with first line platinum-based chemotherapy, Zubrod PS, and disease status after first line treatment as stratification factors. Tissue and blood samples for correlative studies were banked. Results: The study enrolled 73...