Background: Pts with mCRPC often initially receive androgen receptor-targeted therapy (eg, abiraterone or enzalutamide), but they almost always progress. Poly(ADP-ribose) polymerase (PARP) inhibitors (eg, olaparib) have demonstrated clinical activity in pts with mCRPC with a deleterious mutation in a homologous recombination (HR) DNA repair gene; 14 of 16 evaluable pts with mCRPC and a tumor alteration in an HR gene, including BRCA1, BRCA2, and ATM, responded to olaparib (Mateo et al. N Engl J Med. 2015;373:1697-708). The PARP inhibitor rucaparib is approved in the US for treatment of pts with ovarian carcinoma that harbors a deleterious BRCA1 or BRCA2 mutation (germline and/or somatic) who have received ≥2 chemotherapies. These data support investigating rucaparib as a treatment option in pts with mCRPC with HRD. Methods: TRITON3 (NCT02975934)is a phase 3 study evaluating rucaparib (600 mg BID) vs physician’s choice (abiraterone, enzalutamide, or docetaxel) in pts with mCRPC who have a deleterious germline or somatic mutation in BRCA1, BRCA2, or ATM as determined by local and/or central testing. All pts must have progressed on abiraterone or enzalutamide in the mCRPC setting; pts who received prior chemotherapy for mCRPC or PARP inhibitor treatment are excluded. Pts will be randomized 2:1 to rucaparib or physician’s choice of comparator therapy; pts randomized to physician’s choice may cross over to rucaparib on radiographic progression confirmed by independent radiology review (IRR). The primary endpoint is IRR-confirmed radiographic progression-free survival (modified RECIST version 1.1/PCWG3 criteria). Secondary objectives include overall survival, objective response rate, duration of response, clinical benefit rate, pt-reported outcomes, and safety. Pretreatment blood samples will be collected from all pts to enable development of a plasma-based companion diagnostic to identify pts who may benefit from rucaparib treatment. Pts (≈400) will be enrolled at > 100 sites worldwide. Clinical trial information: NCT02975934