Background: About 30% of sporadic mCRPC has defects in DNA repair pathways which may confer sensitivity to PARP inhibition. There is limited data about PDL1 inhibition in mCRPC. We hypothesize increased DNA damage by olaparib (O) will complement anti-tumor activity of immune checkpoint blocking antibody, durvalumab (D), in mCRPC:NCT02484404. Methods: Single arm pilot study with accrual of 25 patients (pts) with mCRPC and biopsiable disease. Prior treatment with enzalutamide and/or abiraterone is required. D is given at 1500 mg iv q28 days + O 300 mg po q12 h. Primary endpoint is PFS. Pretreatment and on-study core biopsies undergo mutational analysis. Results: 10 pts have enrolled (median age 65 yr [range 51-79], median baseline PSA: 85.78 [22.17-809.9 ng/mL]). 7 pts have GS ≥ 8. Grade 3/4 adverse events include anemia 2/7 (29%), thrombocytopenia, lymphopenia, neutropenia, nausea, fatigue, UTI, and lung infection [1/7 each, (14%)]. 5/7 pts (71%) on-study >2 months (mos) have PSA declines > 50%. Median PFS is 7.8 mos (95% CI: 1.8 mos-undefined). Conclusions: Preliminary data shows D+O is well tolerated with activity in an unselected population. Accrual is ongoing with biomarker analysis. Clinical trial information: NCT02484404