Background: Olaparib was approved in 2019 as maintenance therapy for gBRCA1/2+ metastatic pancreatic cancer (mPDA) patients (pts). The POLO trial showed an improvement in median progression free survival (mPFS) with olaparib compared to placebo (7.4 vs 3.8 months) for platinum sensitive gBRCA1/2+ mPDA pts. 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. Several clinical studies in solid tumors have shown preliminary efficacy with the combination of PARP plus immune checkpoint inhibitors. Based upon these data, SWOG S2001 aims to further improve the PFS of gBRCA1/2+ mPDA pts. Methods: S2001 was developed in collaboration with the Alliance and was activated in SWOG in December 2020. Key eligibility criteria include: mPDA pts with gBRCA1/2 pathogenic variants identified with standard of care germline genetic testing and progression-free after receiving at least 16 weeks of platinum-based chemotherapy (FOLFIRINOX, FOLFOX or gemcitabine/cisplatin +/- nab-paclitaxel). One cycle of gemcitabine and nab-paclitaxel is allowed while waiting for germline testing. Zubrod performance status (PS) 0 or 1 pts are eligible. Pts are stratified according to first line chemotherapy, PS 0 vs 1, and disease status after 1st line treatment. The primary objective of this study is to compare PFS in mPDA pts treated with olaparib + pembrolizumab versus olaparib alone as maintenance therapy. Based upon the POLO trial, we expect a mPFS of 7 months in the control arm. Targeting a mPFS of 11.7 months in the experimental arm (hazard ratio 0.6) and assuming 15 months follow-up, 80% power and a 1-sided alpha=0.10, this design requires enrolling 88 pts for a total of 78 eligible and evaluable pts. As of February 2023, 26 participants have been accrued. Prospective serial blood samples will be collected to bank DNA and RNA for future correlative studies. Clinical trial information: NCT04548752.