An Open-label Study Comparing 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 will enroll adult participants with PSMA PET 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 CRPC setting. A PSMA PET/ computed tomography (CT) scan will be done at Screening to confirm PSMA positive disease. This is a United States-based study.

Approximately 420 eligible participants will be randomized in a 1:1 ratio to one of the two treatment arms (Arm A: AAA617+ARPI vs Arm B: AAA617). The primary objective of the study is to evaluate the rPFS response in participants with metastatic CRPC, assessed by conventional imaging, treated with AAA617 in combination with ARPI and AAA617 alone. Best Supportive Care (BSC) will be allowed in both arms at the discretion of the investigator and includes available care for the eligible participants according to best institutional practice for mCRPC. Androgen deprivation therapy (ADT) is required in both arms.

A total of approximately 420 eligible participants will be 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 will be 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 \[BCR-non mHSPC or nmCRPC setting\]).

The study duration is approximately 3.5 years.