Phase I/II Study of [225Ac]Ac-PSMA-R2 in PSMA-positive Prostate Cancer, With/Without Prior 177Lu-PSMA RLT

Key Inclusion Criteria:

• Evidence of PSMA-positive disease by 68Ga-PSMA-11 PET/CT and eligible as determinedby central reading

• Documented progressive mCRPC or mHSPC

• Adequate organ function

• Prior orchiectomy or ongoing ADT and should have received prior 177Lu-PSMA-RLT (Group1 dose escalation & expansion) or never received 177Lu-PSMA-RLT (Group 2 andGroup 3 dose escalation & expansion).

Key Exclusion Criteria:

• Any other investigational agents within 28 days of the anticipated C1D1 of 225Ac-PSMA-R2 therapy

• Any systemic anti-cancer therapy within 28 days of the anticipated C1D1 of 225Ac-PSMA-R2 therapy

• Uncontrolled pain or incompatibility that may result in participant's lack ofability to comply with imaging procedures

• History of CNS metastases and symptomatic cord compression, or clinical orradiologic findings indicative of impending cord compression

• History of myocardial infarction, angina pectoris, or coronary artery bypass graftwithin 6 months prior to ICF signature and/or clinically active significant cardiacdisease

• Diagnosis of other malignancies in the past three years expected to alter lifeexpectancy or may interfere with disease assessment

Other protocol-defined inclusion/exclusion criteria may apply.