Trial of ARV-110 and Abiraterone in Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC)

Inclusion Criteria: 1. Histological, pathological, or cytological confirmed diagnosis of adenocarcinoma of the prostate. 2. Ongoing treatment with stable doses of abiraterone (on an empty stomach) and a concomitant corticosteroid for metastatic castration-resistant prostate cancer (mCRPC) or for metastatic castration sensitive prostate cancer (mCSPC) until Cycle 1, Day 1 (C1D1). 3. Recent PSA values must demonstrate: 1. Rising PSAs at least 16 weeks after initiation of abiraterone 2. At least 2 PSA values that are higher than the PSA nadir on abiraterone, measured at a minimum of 1 week apart . The screening PSA for this study may be used as the 2nd PSA value. 4. No known radiographic evidence of disease progression while receiving abiraterone and clinically benefitting at the time of consent. If there is radiographic disease progression during screening, the patient may be considered eligible if, in the judgement of the investigator, the patient is clinically benefitting from abiraterone. 5. Ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) analogue or inhibitor, or orchiectomy (surgical or medical castration). 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Exclusion Criteria: 1. Previously treated with enzalutamide, apalutamide, darolutamide or experimental therapies (e.g., protein degraders or inhibitors) directed at the AR. 2. Treatment with any chemotherapy, investigational agents, immunotherapy, or hormonal therapy other than GnRH agonists within 28 days of the start of treatment on protocol. 3. Radiation therapy within 4 weeks of first dose of study drug or prior irradiation to \>25% of the bone marrow. 4. Patients taking agents that are either a) sensitive P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) substrates, or CYP3A4 substrates, b) P-gp, BCRP, CYP3A4, or CYP2D6 substrates that have a narrow therapeutic index, c) strong CYP3A4 inhibitors or inducers, or d) any other prohibited and/or restricted medications described in the protocol. 5. Major surgery (as judged by the Investigator) within 4 weeks of first dose of study drug. 6. Untreated brain metastases or brain metastases requiring steroids 7. Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ. 8. Any of the following in the previous 12 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association class II, III or IV), cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism, or other clinically significant episode of thromboembolic disease. 9. Any of the following in the previous 6 months: congenital long QT syndrome, Torsade de Pointes, arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation), left anterior hemiblock (bifascicular block), or ongoing cardiac dysrhythmias of National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) Grade ≥2, atrial fibrillation of any grade (Grade ≥2 in the case of asymptomatic lone atrial fibrillation).. 10. Hypertension that cannot be controlled by medications (\>150/90 mmHg despite optimal medical therapy). 11. Active, uncontrolled bacterial, fungal, or viral infection, including hepatitis B virus, hepatitis C virus, known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS)-related illness. 12. Active inflammatory gastrointestinal disease, uncontrolled chronic diarrhea, known diverticular disease, or previous gastric resection or lap band surgery. Gastroesophageal reflux disease is allowed except for if under treatment with proton pump inhibitors. 13. Patients with Child Pugh C. 14. Patients with electrolyte imbalances of hypokalemia, hypomagnesemia, and/or hypocalcemia. 15. Patients with QTcF ≥470 msec.