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

This is an open label, phase I/II, multi-center study in adult participants with metastatic hormone sensitive prostate cancer (mHSPC) and with metastatic castration resistant prostate cancer (mCRPC) who have received prior anti-cancer treatment and have a positive 68Ga-PSMA-11 PET scan. The purpose of this study is to learn if the study drug, \[225Ac\]Ac-PSMA-R2, is safe and tolerable, and has anti-tumor activity in treated patients. Enrollment of all participants was not completed. The evaluated radioligand showed acceptable safety but limited benefit in metastatic prostate cancer

The study contains three groups (Group 1, Group 2, and Group 3). Each group has a dose escalation part at a specific dosing schedule followed by a dose expansion part. The dose escalation parts in each group within each dosing schedule will establish the maximum tolerated dose or the recommended dose for expansion (MTDs/RDEs) of the 225Ac-PSMA-R2. Dose escalation decisions will be made by the Investigators and Novartis during dose escalation meetings (DEMs) based on safety and tolerability information. The dose expansion parts in each group group/dosing schedule will assess the anti-tumor activity in the mHSPC and mCRPC populations.

Key Inclusion Criteria: * Evidence of PSMA-positive disease by 68Ga-PSMA-11 PET/CT and eligible as determined by 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 and Group 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 of ability to comply with imaging procedures * History of CNS metastases and symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression * History of myocardial infarction, angina pectoris, or coronary artery bypass graft within 6 months prior to ICF signature and/or clinically active significant cardiac disease * Diagnosis of other malignancies in the past three years expected to alter life expectancy or may interfere with disease assessment Other protocol-defined inclusion/exclusion criteria may apply.