An Open-label Study of Lutetium (177Lu) Vipivotide Tetraxetan (AAA617) in Combination With ARPI Versus AAA617 in PSMA Positive First-line mCRPC

This prospective, open-label, multi-center, randomized phase II study enrolled adult participants with PSMA PET (positron emission tomography) positive mCRPC who were previously treated and progressed on ARPI in the BCR-non mHSPC, mHSPC, or nmCRPC setting and have not previously received a taxane-containing regimen in the mCRPC setting. A PSMA PET/ computed tomography (CT) scan was done at Screening to confirm PSMA positive disease. This is a United States-based study. Eligible participants were randomized in a 1:1 ratio to one of the two treatment arms (Arm A: AAA617+ARPI vs Arm B: AAA617). As the study is being closed out early, safety and tolerability will be assessed in already enrolled participants, treated with AAA617 in combination with ARPI or AAA617 alone. In Arm A, participants will receive ARPI between Day -14 and prior to first dose of AAA617 and will continue until a maximum of Cycle 6 Day 42 of AAA617, until the treatment is no longer clinically beneficial to participant, or experiences unacceptable toxicity or as per investigator's decision, whichever is earliest. The ARPI (abiraterone or enzalutamide) was as per investigator's choice, and switching from prior ARPI (pre-randomization) was highly recommended. Seven eligible participants were randomized in a 1:1 ratio into one of two treatment arms. Participants in Arm A will receive AAA617 in combination with ARPI, while those in Arm B will receive AAA617 alone. Randomization was stratified by type of prior ARPI (abiraterone vs other \[enzalutamide, apalutamide, or darolutamide\]) and by setting of prior ARPI (mHSPC without docetaxel vs mHSPC with docetaxel vs others \[BCRnon mHSPC or nmCRPC setting\]). The study duration is approximately 1.5 years.