Combination of PDL-1 and PARP inhibition in an unselected population with metastatic castrate-resistant prostate cancer (mCRPC).

• DOI: 10.1200/jco.2017.35.15_suppl.5026
• Publication Date: 2018-09-06T15:45:33Z
• Authors: Fatima Karzai; Ravi Amrit Madan; Helen Owens; Amy Hankin; Anna Couvillon; Lisa M Cordes; Farhad Fakhrejahani; Nicole D. Houston; Jane B. Trepel; Clara Chen; Daniel C. Edelman; Paul S. Meltzer; Seth M. Steinberg; James L. Gulley; William L. Dahut; Jung-min Lee
• Keywords: Olaparib; Durvalumab; Enzalutamide; Clinical endpoint; PARP inhibitor

5026 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 mCRPC. We hypothesize increased damage by olaparib (O) will complement anti-tumor activity immune checkpoint blocking antibody, durvalumab (D), mCRPC:NCT02484404. Methods: Single arm pilot study with accrual 25 patients (pts) and biopsiable disease. Prior treatment enzalutamide and/or abiraterone required. D given at 1500 mg iv q28 days + O 300 po q12 h. Primary endpoint PFS. Pretreatment 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 GS ≥ 8. Grade 3/4 adverse events include anemia 2/7 (29%), thrombocytopenia, lymphopenia, neutropenia, nausea, fatigue, UTI, lung infection [1/7 each, (14%)]. 5/7 (71%) >2 months (mos) PSA declines > 50%. Median PFS 7.8 mos (95% CI: 1.8 mos-undefined). Conclusions: Preliminary shows D+O well tolerated an unselected population. Accrual ongoing biomarker Clinical trial information: NCT02484404. [Table: see text]