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

• Status: Recruiting
• Trial end date: 2023-11-01
• Target enrollment: 0
• Participant gender: Male

Summary

Phase 1b study to assess the combination of ARV-110 and abiraterone in patients with metastatic prostate cancer with PSA progression on abiraterone.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Arvinas Androgen Receptor, Inc.

Criteria

Inclusion Criteria:

1. Histological, pathological, or cytological confirmed diagnosis of adenocarcinoma of the prostate.

2. Ongoing treatment with stable doses of abiraterone and a concomitant corticosteroid for metastatic castration-resistant prostate cancer (CRPC) or for castration sensitive prostate cancer CSPC until Cycle 1, Day 1 (C1D1).

3. Recent PSA values prior to signing consent must demonstrate:

1. PSA progression no less than 16 weeks after initiation of abiraterone

2. A sequence of at least 2 rising PSA values measured at a minimum of 1 week apart (if PSA is <2 ng/ml, a sequence of at least 3 rising PSA values measured a minimum of 1 week apart is required)

4. No known radiographic evidence of disease progression while receiving abiraterone (prior to signing consent for this study).

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 P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) substrates, CYP3A4 substrate, CYP2D6 substrate that have a narrow therapeutic index, strong CYP3A4 inhibitors or inducers.

5. Major surgery (as judged by the Investigator) within 4 weeks of first dose of study drug.

6. 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.

7. 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). Anticoagulation (heparin/lovenox only, no vitamin K antagonists or factor Xa inhibitors) can be allowed if indicated.

8. Hypertension that cannot be controlled by medications (>150/90 mmHg despite optimal medical therapy).

9. 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.

10. Active inflammatory gastrointestinal disease, uncontrolled chronic diarrhea, known diverticular disease, or previous gastric resection or lap band surgery. Gastroesophageal reflux disease under treatment with proton pump inhibitors is allowed.

11. Patients with Child Pugh C.