AZD2265 Compared With Standard of Care in PSMA-positive Metastatic Castration-resistant Prostate Cancer (VECTRA-01)

The intention of the study is to demonstrate superiority of AZD2265 relative to standard of care treatments by assessment of radiographic progression-free survival (rPFS) and overall survival (OS) in participants with mCRPC.

Inclusion Criteria: * ≥ 18 years of age. * Diagnosis of adenocarcinoma of prostate. * Must have had prior orchiectomy and/or ongoing ADT and a castrate level of plasma/serum testosterone. * Progressive mCRPC following the most recent treatment at the time of study entry, with at least 1 metastatic lesion (measurable and/or non-measurable) that is suitable for repeated assessment by CT and/or MRI and/or bone scan. * Previously treated with at least 2 cycles of PSMA-directed β-emitting radioconjugate. * Previously treated with at least 1 taxane-based chemotherapy regimen for either metastatic hormone-sensitive prostate cancer or CRPC. * Previously treated with at least 1 ARPI (eg, enzalutamide, abiraterone, etc.). * Positive PSMA PET/CT scans, obtained with PSMA ligands (⁶⁸Ga-PSMA-11 or ¹⁸F-DCFPyL). * ECOG performance status of 0 to 2. * Adequate organ and bone marrow function as described in study protocol. * Participants must not father children or donate sperm from signing ICF, during the study intervention and for 6 months after the last dose of study intervention. * Participants must use a condom from signing ICF, during study intervention, and for 6 months after the last dose of study drug, with all sexual partners. Exclusion Criteria: * Prior treatment with an α-emitting molecular targeted therapeutic radioconjugate (prior treatment with radium-223 is permitted). * Progression on PSMA-directed β-emitting radioconjugate prior to the administration of Cycle 3. * Receipt of \> 6 cycles of PSMA-directed β-emitting therapeutic RC. * History of another primary malignancy, with exceptions. * Persistent toxicities (CTCAE Grade ≥ 2) caused by previous anticancer therapy, with exceptions. * Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to start of study intervention. * Clinically significant ECG abnormalities, with exceptions.