A phase 2 study of olaparib and durvalumab in metastatic castrate-resistant prostate cancer (mCRPC) in an unselected population

163 Background: Data suggests 25-30% of sporadic mCRPC has defects in DNA repair pathways which may confer sensitivity to PARP inhibition (PARPi). Immune checkpoint blockade may increase the proportion of patients that respond to PARPi. We hypothesize that 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 disease that is amenable to biopsy. Prior treatment with enzalutamide and/or abiraterone is required. D is given at 1500 mg iv q28 days + O 300 mg tablets po q12 hours. The primary endpoint is PFS. Core biopsies undergo mutational analysis. Results: In the first 17 pts, median age is 66 (range 45-79 years), median baseline PSA is 79.67 ng/mL [3.93-2356 ng/mL]). Median Gleason score is 8. 6 patients have bone only disease and 11 patients have bone and soft tissue/visceral disease. Median number of cycles is 7 (2-17). Grade 3/4 adverse events include anemia 4/17 (24%), lymphopenia 2/17 (12%), infection 2/17 (12%), thrombocytopenia, leukopenia, neutropenia, nausea, vomiting, UTI, hypertension, hearing impairment, fatigue, syncope, oral mucositis, muscle weakness, and muscle cramps [1/17 each, (6%)]. 8/17 pts (47%) had PSA responses >50%. 6 of these pts had mutations in the DNA damage repair pathways (DNAdr). 2/17 pts (11%) had PSA responses >30% with no known mutations in DNAdr. 4 pts had a PR. The 12 month PFS is 51.5% (95% CI: 25.7-72.3%). 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.