Title
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

Description
The study will evaluate ARV-766 given once or twice daily to cohorts of patients in escalating doses. Each dose level will have safety assessed and if found safe and tolerable, the next cohort of patients will be enrolled at a higher dose level. Increasing dose levels will be evaluated until the highest safe dose is identified. Patients treated at lower doses may increase to the next higher dose level once it is determined to be safe, provided they have been on their current dose for 28 or more days and have no major side effects.

Objective

Incidence of Dose Limiting Toxicities of ARV-766 [ Time Frame: 28 Days ]


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


Number of Patients with Adverse Events as a measure of safety and tolerability of ARV-766 [ Time Frame: 28 Days ]


Adverse events as characterized by type, frequency, severity (as graded by NCI CTCAE v 5.0), timing, seriousness, and relationship to study drug.


Incidence of laboratory abnormalities as a measure of safety and tolerability of ARV-766 [ Time Frame: 28 Days ]


Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v 5.0), and timing.

Treatment Experimental: ARV-766
Oral tablet(s), once or twice daily in 28 day cycles

Key Eligibility Inclusion Criteria:

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

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

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

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

Applicable Disease Sites
Prostate

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital