NCT06894511

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

A Phase II, Open-label, Multi-Center, Randomized Study Comparing the Combination of Lutetium (177Lu) Vipivotide Tetraxetan (AAA617) and Androgen Receptor Pathway Inhibitor (ARPI) vs. Lutetium (177Lu) Vipivotide Tetraxetan (AAA617) in First-line Treatment of Patients With Prostate-Specific Membrane Antigen (PSMA)-Positive Progressive Metastatic Castration Resistant Prostate Cancer (mCRPC)

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 7 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: Male
• Age: 18 Years – 100 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to assess whether the combination of AAA617 (administered for 6 cycles at a dose of 7.4 GBq (200 mCi) +/- 10%) and ARPI improves radiographic progression-free survival (rPFS) or time to death compared to AAA617 alone in PSMA-positive mCRPC patients who were previously treated and progressed on ARPI in the biochemical recurrence (BCR)-non metastatic hormone sensitive prostate cancer (mHSPC), mHSPC, or non-metastatic Castration Resistant Prostate Cancer (nmCRPC) setting and have not previously received a taxane-containing regimen in the castrate resistant prostate cancer (CRPC) setting.

Detailed description

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.

Conditions

• Metastatic Castration Resistant Prostate Cancer (mCRPC)

Interventions

Type	Name	Description
DRUG	AAA617	Dose formulation: open-label vial Dose level: 7.4 GBq (200 mCi) ± 10% Once, every 6 weeks for 6 cycles, intravenous administration
DRUG	ARPI: Abiraterone	Dose formulation: tablet/capsule Dose level: 160 mg (four 40 mg or two 80 mg soft capsules) as a single daily dose, oral administration
DRUG	ARPI: Enzalutamide	Dose formulation: tablet Dose level: 1000 mg daily (two 500 mg tablets or four 250 mg tablets as a single daily dose together with 5 mg oral prednisone 2 times a day, oral administration

Timeline

• Start date: 2025-09-11
• Primary completion: 2029-04-09
• Completion: 2029-04-09
• First posted: 2025-03-25
• Last updated: 2026-04-08

Locations

5 sites across 1 country: United States

Regulatory

• FDA-regulated drug study