A Study of ARV-766 Given by Mouth in Men With Metastatic Prostate Cancer

Study Overview
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Brief Summary
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A Phase 1/2 study to evaluate the safety and efficacy of ARV-766 given by mouth alone or in combination with abiraterone in men with metastatic prostate cancer.

Official Title
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A Phase 1/2 Open-Label, Dose-Escalation and Cohort Expansion Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ARV-766 Monotherapy and in Combination With Abiraterone in Patients With Metastatic Prostate Cancer

Conditions
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Prostate Cancer Metastatic

Intervention / Treatment
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* Drug: ARV-766 Part A&B
* Drug: ARV-766 + Abiraterone Part C&D


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Part A,B,C and D: Histological, pathological, or cytological confirmed diagnosis of adenocarcinoma of the prostate. Ongoing androgen deprivation therapy (ADT) with a gonadotropin releasing hormone analog or inhibitor, or orchiectomy (surgical or medical castration). Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Part A: Progression on at least 2 prior approved systemic therapies for metastatic prostate cancer (at least one must be a second-generation androgen inhibitor, e.g., abiraterone, enzalutamide, darolutamide, apalutamide). Progressive mCRPC Part B: Participants must have received at least one but no more than three prior second generation anti-androgen agents (e.g., enzalutamide or abiraterone). Participants must have received no more than two prior chemotherapy regimens. Progressive mCRPC Part C & D: • Metastatic castration resistant or sensitive prostate cancer with radiographic evidence of metastatic disease Exclusion Criteria: Part A and B: Known symptomatic brain metastases requiring steroids (above physiologic replacement doses). Active inflammatory gastrointestinal disease, chronic diarrhea, known diverticular disease, or previous gastric resection or lap band surgery. Radiation therapy within 4 weeks of first dose of study drug or prior irradiation to >25% of the bone marrow. Receipt of an investigational drug(s) within 4 weeks prior to anticipated first dose Systemic anti-cancer therapy within 2 weeks of first dose of study drug (except agents to maintain castrate status). For bicalutamide, mitomycin C, or nitrosoureas the exclusion period must be 6 weeks and for abiraterone 4 weeks. Part C and D • Prior treatment with a second generation NHA

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARV-766<br>Oral tablets, once daily in 28 day cycles | Drug: ARV-766 Part A&B<br>* Part A: Daily oral dosages are determined by cohort review committee after initial starting dose cohort and each subsequent cohort completes 28 days of treatment. Part B: Oral tablet(s) once daily in 28 day cycles.<br>|
| Experimental: ARV-766 + Abiraterone<br>Oral tablets, once daily in 28 day cycles | Drug: ARV-766 + Abiraterone Part C&D<br>* Part C: Daily oral combination dosages are determined by cohort review committee after initial starting dose cohort and each subsequent cohort completes 28 days of treatment. Part D: Combination administered once daily in 28 day cycles. Parts C&D: Participants will also receive concomitant corticosteroid and ADT therapy of investigator choice/patient preference<br>* Other names: Corticosteroid and ADT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Incidence of Dose Limiting Toxicities of ARV-766 | First Cycle Dose limiting toxicities characterized by type, frequency, severity (as graded by NCI CTCAE v 5.0), timing, seriousness, and relationship to study drug | 28 Days | 
| Part A: Number of Patients with Adverse Events as a measure of safety and tolerability of ARV-766 | Adverse events as characterized by type, frequency, severity (as graded by NCI CTCAE v 5.0), timing, seriousness, and relationship to study drug. | 28 Days | 
| Part A: Incidence of laboratory abnormalities as a measure of safety and tolerability of ARV-766 | Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v 5.0), and timing. | 28 Days | 
| Part B: To evaluate the clinical anti-tumor activity of ARV-766 in patients with mCRPC | Evaluate PSA in patients with mCRPC in both dose groups | 12 Weeks | 
| Part C: Incidence of Dose Limiting Toxicities of ARV-766 / abiraterone combination | First Cycle Dose limiting toxicities characterized by type, frequency, severity (as graded by NCI CTCAE v 5.0), timing, seriousness, and relationship to study drug | 28 Days | 
| Part C: Incidence of laboratory abnormalities as a measure of safety and tolerability of ARV-766 / abiraterone combination | Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v 5.0), and timing. | 28 Days | 
| Part C: Number of Patients with Adverse Events as a measure of safety and tolerability of ARV-766 / abiraterone combination | Adverse events as characterized by type, frequency, severity (as graded by NCI CTCAE v 5.0), timing, seriousness, and relationship to study drug. | 28 Days | 
| Part D: To evaluate the clinical anti-tumor activity of ARV-766 / abiraterone combination in patients with NHA-naïve mPC | Evaluate PSA in patients with NHA-naïve mPC | 12 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostatic Neoplasms, Metastatic Prostate Cancer, Castrate-Resistant, Prostate Cancer, mCRPC adenocarcinoma of prostate, Genital Neoplasms, Male, Urogenital Neoplasms, Castrate-Sensitive, mCSPC adenocarcinoma of prostate