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

This first-in-human, Phase 1/2, open-label study evaluates the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of JSB462 (luxdegalutamide, previously ARV-766) administered as monotherapy and in combination with abiraterone in participants with metastatic prostate cancer. The study includes dose-escalation and cohort expansion components to determine the recommended Phase 2 dose and assess clinical activity.

Key Inclusion Criteria for Parts A, B, and C: * Participants must be able to take oral medication without crushing, dissolving, or chewing tablets * Histological, pathological, or cytological confirmed diagnosis of adenocarcinoma of the prostate * Progression on approved systemic therapies for metastatic prostate cancer (at least one must be a second-generation androgen inhibitor, e.g., abiraterone, enzalutamide, darolutamide, apalutamide) (Parts A and B only) * Progressive mCRPC (Parts A and B only) defined as: * Serum testosterone levels \480 msec at baseline based on ECG * Active inflammatory gastrointestinal disease, chronic diarrhea, diverticulitis, or previous gastric resection or lap band surgery * Participants taking sensitive BCRP and P-glycoprotein (P-gp) substrates or substrates with narrow therapeutic indices, strong CYP3A4 inhibitors and inducers, restricted medications described in the study protocol and the Investigator's Brochure, and additionally for Part C, CYP2D6 substrates with a narrow therapeutic index * Inadequate bone marrow function defined as follows (with no transfusion of blood products or use of hematopoietic growth factors in the 28 days prior to start of therapy): * Absolute neutrophil count \