Participants must be adults ≥ 18 years of age with signed informed consent prior to participation to study

Histologically or cytologically confirmed prostate cancer

Participants must have ongoing androgen deprivation therapy with a GnRH agonist/antagonist or prior bilateral orchiectomy

Castrate level of serum testosterone (< 1.7 nmol/L [50 ng/dL]) on GnRH agonist or antagonist therapy or after bilateral orchiectomy

Participants must have evidence of PSMA-positive disease as seen on a AAA517 or piflufolastat (18F) PET/CT scan at baseline as determined by Blinded Independent Central Review (BICR) based on the methodology proposed in the Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) (Eiber et al 2018). Participants with M1 disease only on PSMA PET scan are allowed to participate

Participants must have a negative conventional imaging for M1 disease.

PSA Doubling Time (PSADT) of ≤ 10 months

Participants must have adequate organ functions: bone marrow reserve, hepatic & renal

Prior or present evidence of metastatic disease as assessed by CT/MRI locally for soft tissue disease and whole-body radionuclide bone scan for bone disease. Exception: Participants with soft tissue pelvic disease may be eligible (e.g., participants with enlarged lymph nodes below the common iliac bifurcation (N1) are eligible if the short axis of the largest lymph node is <20 mm, per AJCC 8 definition of local disease)

Unmanageable concurrent bladder outflow obstruction or urinary incontinence. Note: participants with bladder outflow obstruction or urinary incontinence, which is manageable with best available standard of care (incl. pads, drainage) are allowed

Active clinically significant cardiac disease; history of seizure or condition that may predispose to seizure which may require treatment with surgery or radiation therapy

Prior therapy with: second generation anti-androgens (e.g., enzalutamide, apalutamide and darolutamide); CYP17 inhibitors (e.g., abiraterone acetate, orteronel, galeterone, ketoconazole; radiopharmaceutical agents (e.g., Strontium-89), PSMA-targeted radioligand therapy; immunotherapy (e.g., sipuleucel-T); chemotherapy, except if administered in the adjuvant/neoadjuvant setting, completed > 2 years before randomization; any other investigational agents for CRPC; use of estrogens, 5-α reductase inhibitors (finasteride, dutasteride), other steroidogenesis inhibitors (aminoglutethimide) or first-generation anti-androgens (bicalutamide, flutamide, nilutamide, cyproterone) within 28 days before randomization; radiation therapy (external beam radiation therapy [EBRT] and brachytherapy within 28 days before randomization

Other concurrent cytotoxicity chemotherapy, immunotherapy, radioligand therapy, poly adenosine diphosphate-ribose polymerase (PARP) inhibitor, biological therapy or investigational therapy