Olaparib + PD-1 blockade (pembrolizumab) misses PFS bar in gBRCA metastatic PDAC maintenance

SWOG S2001 (NCT04548752) randomized Phase II tested maintenance olaparib (PARP inhibitor) 300mg BID plus pembrolizumab (PD-1) Q3W vs olaparib alone in metastatic pancreatic ductal adenocarcinoma with germline BRCA1/2 after ≥4 months of non-progressing platinum (n=68 eligible; 34/arm). Median PFS was 8.2 vs 6.4 months (p=0.82; trial stopped early for futility) with ORR 28.1% vs 14.3% (p=0.20), DCR 84.4% vs 64.3%, and median OS 20.0 vs 22.1 months. Safety was similar with no grade 4–5 TRAEs; immune toxicities on the combo included adrenal insufficiency and thyroid dysfunction, while grade 3 AEs in both arms included cytopenias, GI toxicity, and fatigue—overall efficacy is broadly in the range expected for olaparib maintenance in this biomarker-selected setting (POLO: mPFS 7.4 months vs placebo 3.8 months).