Open-label Study Comparing AAA817 Versus Standard of Care in the Treatment of Previously Treated PSMA-positive mCRPC Adults Who Have Disease Progressed on or After [177Lu]Lu-PSMA Targeted Therapy

Inclusion Criteria: ∙

• adults ≥ 18 years of age.

• ECOG performance status of 0 to 2.

• histopathological and/or cytological confirmation of adenocarcinoma of the prostate.

• PSMA-positive disease as assessed by PSMA PET/CT scan using an approved PSMA imagingagent as protocol instructed,

• castrate level of serum/plasma testosterone (< 50 ng/dL or < 1.7 nmol/L).

• Prior treatments with an androgen receptor pathway inhibitor (ARPI) and taxane-basedchemotherapy, and progressed on or after [177Lu]Lu-PSMA targeted therapy.

• ≥ 1 metastatic lesion that is present on screening/baseline CT, MRI, or bone scanimaging obtained ≤ 28 days prior to randomization

• eGFR as requested by the sponsor

Exclusion Criteria:

• Any investigational agents within 28 days prior to the day of randomization.

• Any 225Ac-based investigational compound used prior to the day of randomization.

• Participants with a history of CNS metastases who are neurologically unstable,symptomatic, or receiving corticosteroids for the purpose of maintaining neurologicintegrity.

• Concurrent acute kidney injury (renal failure developed between 48 hours to 7 days)or chronic kidney disease (at least 3 months of ongoing renal injury)

• Baseline xerostomia ≥ Grade 2 by CTCAE v.5

• History of uncontrolled hypertension, myocardial infarction (MI), angina pectoris,or coronary artery bypass graft (CABG) within 6 months prior to ICF signature and/orclinically active significant cardiac disease

• History of lymphoproliferative disease or any known malignancy or history ofmalignancy of any organ system within the past 5 years (except for basal cellcarcinoma or actinic keratosis that have been treated with no evidence of recurrencein the past 3 months, non-invasive malignant colon polyps that have been removed).

Other protocol-defined inclusion/exclusion criteria may apply.