Study Comparing AAA817+ARPI Versus Standard of Care in Adult Participants With PSMA-positive mCRPC

Required: FOLH1 overexpression (PSMA-PET positive disease)

Participants must have PSMA-PET positive disease using a PSMA imaging agent that is approved as per protocol.

Must have received: androgen receptor pathway inhibitor — mHSPC or earlier

diagnosed with mCRPC with documented progressive disease while on treatment with ARPI in mHSPC or earlier setting as their last treatment (and did not progress on more than one ARPI)

Cannot have received: taxane-based chemotherapy

Exception: allowed in mHSPC setting if appropriate for chemotherapy, ARPI change or AAA617 as next line of therapy

Participants must not have received taxane-based chemotherapy in mCRPC setting (allowed in mHSPC setting).

Cannot have received: radiopharmaceutical ([177Lu]Lu-PSMA, [177Lu]-DOTA, Radium-223)

Previous anti-cancer treatment with any approved or investigational radiopharmaceuticals (for example, [177Lu]Lu-PSMA, [177Lu]-DOTA, or Radium-223.)

Cannot have received: external beam radiotherapy

Exception: localized metastases allowed if >2 weeks before randomization

Previous treatment with any external beam radiotherapy including hemi-body radiation within 6 weeks of randomization (within 2 weeks for radiotherapy of localized metastases).

Cannot have received: PARP inhibitor

Any prior PARP inhibitor or other systemic anticancer therapy administered for metastatic castration-resistant prostate cancer (mCRPC).

Cannot have received: systemic anticancer therapy

Exception: ARPI administered in the mHSPC setting or earlier may continue until C1D1

Any other approved or investigational systemic therapy (including chemotherapy, immunotherapy, biologics, or monoclonal antibodies) is prohibited within 28 days or 5 half-lives (whichever is shorter) before randomization.