PLX2853 in Combination With Abiraterone Acetate and Prednisone and in Combination With Olaparib in Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC)

1. Age ≥18 years at the time of signing informed consent.
2. Histologically confirmed adenocarcinoma of the prostate with tumor tissue available for molecular analyses.
3. Eastern Cooperative Oncology Group Performance Status 0 to 1.
4. Adequate organ function as demonstrated following laboratory values.
5. Fertile male subjects with female sexual partners must agree to use a highly effective method of birth control during the study and for 90 days after the last dose of study drug.
6. Except as specified above for organ function, all drug-related toxicity from previous cancer therapy (including ongoing Abiraterone Acetate + Prednisone therapy if applicable) must be resolved (to Grade ≤1 or baseline per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0) prior to study treatment administration (Grade 2: alopecia, hot flashes, decreased libido, or neuropathy is allowed).
7. Willingness and ability to provide written informed consent prior to any study-related procedures and to comply with all study requirements.

Exclusion Criteria:

1. Prior exposure to a bromodomain inhibitor.
2. History of autoimmune hemolytic anemia or autoimmune thrombocytopenia.
3. Clinically significant cardiac disease.
4. Inability to take oral medication or significant nausea and vomiting, malabsorption, or significant small bowel resection that, in the opinion of the Investigator, would preclude adequate absorption.

5. Active known second malignancy with the exception of any of the following:

   • Adequately treated basal cell carcinoma or squamous cell carcinoma of the skin.
   • Adequately treated Stage I cancer from which the subject is currently in remission and has been in remission for ≥2 years.
   • Any other cancer from which the subject has been disease-free for ≥3 years.
6. Subject is participating in any other therapeutic clinical study (observational or registry studies are allowed).
7. Presence of any other medical, psychological, familial, sociological, or geographic condition potentially hampering compliance with the study protocol or would interfere with the study endpoints or the subject's ability to participate in the study in the judgment of the Investigator.
8. Receipt of any anti-cancer therapy prior to Cycle 1 Day 1 with less than protocol defined wash-out with the exception of Abiraterone Acetate (for subjects enrolling into Abiraterone Acetate Combination) and GnRH therapy.