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 versus 3.8 months) for gBRCA1/2+ mPDA pts following either stable disease/response on first-line platinum chemotherapy. 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 October 2020. mPDA pts with gBRCA1/2 mutations identified with standard of care germline genetic testing will be eligibleif no progression after receiving 4 to 6 months of platinum chemotherapy (FOLFIRINOX, FOLFOX or gemcitabine/cisplatin). Zubrod performance status (PS) 0 or 1 pts are eligible. Pts will be stratified according to first line chemotherapy, PS 0 versus 1, and disease status after first-line treatment. The primary objective of this study is to evaluate the PFS of mPDA pts treated with olaparib + pembrolizumab compared to 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 78 evaluable pts to be accrued over 3 years. Prospective serial blood samples will be collected to bank DNA and RNA for future correlative studies. Support:NIH/NCI grants U10CA180888 and U10CA180819. Clinical trial information: TBD.