177Lu-PSMA-617 vs. Androgen Receptor-Directed Therapy in the Treatment of Progressive Metastatic Castrate Resistant Prostate Cancer
Summary
The purpose of this study is to determine whether 177Lu-PSMA-617 improves the Radiographic progression-free survival (rPFS) or Overall Survival (OS) compared to a change in Androgen receptor-directed therapy (ARDT) in metastatic castrate resistant prostate cancer (mCRPC) participants that were previously treated with an alternate ARDT and not exposed to a taxane-containing regimen in the CRPC or mHSPC settings. 469 participants were randomized (235 in the 177Lu-PSMA-617 group and 234 in the ARDT group.
Timeline
- Start
- 2021-06-15
- Primary completion
- 2022-10-02
- Completion
- 2026-09-10
Outcome
Met primary endpoint
registry MEDIAN 177Lu-PSMA-617 (AAA617): 9.30 (6.77 to NA) months NCT04689828 ↗
registry MEDIAN Androgen Receptor-directed Therapy (ARDT): 5.55 (4.04 to 5.95) months NCT04689828 ↗
registry 177Lu-PSMA-617 (AAA617) vs Androgen Receptor-directed Therapy (ARDT); p = 0.00000001 NCT04689828 ↗
paper 177Lu-PSMA-617 prolonged radiographic progression-free survival relative to ARPI change PMID 39293462 ↗
release “Phase III PSMAfore trial with Pluvicto TM met the primary endpoint of radiographic progression-free survival (rPFS) in PSMA–positive mCRPC” novartis.com ↗
release “Phase III PSMAfore trial with Pluvicto™ met its primary endpoint of radiographic progression-free survival (rPFS)” novartis.com ↗
Publications
- Fizazi K, Chi KN, Shore ND, Herrmann K, de Bono JS, Castellano D, Piulats JM, Flechon A, Wei XX, Mahammedi H, Roubaud G, Fleming M, Haas T, Ghebremariam S, Kreisl TN, Rajagopalan S, Sartor O, Morris MJ; PSMAfore Investigators. Final overall survival and safety analyses of the phase III PSMAfore trial of [177Lu]Lu-PSMA-617 versus change of androgen receptor pathway inhibitor in taxane-naive patients with metastatic castration-resistant prostate cancer. Ann Oncol. 2025 Nov;36(11):1319-1330. doi: 10.1016/j.annonc.2025.07.003. Epub 2025 Jul 17.
- Fizazi K, Morris MJ, Shore ND, Chi KN, Crosby M, de Bono JS, Herrmann K, Roubaud G, Nagarajah J, Fleming M, Lewis B, Nordquist L, Carnahan N, Ghebremariam S, Hertelendi M, Castellano D, Sartor O. Health-related quality of life, pain, and symptomatic skeletal events with [177Lu]Lu-PSMA-617 in patients with progressive metastatic castration-resistant prostate cancer (PSMAfore): an open-label, randomised, phase 3 trial. Lancet Oncol. 2025 Jul;26(7):948-959. doi: 10.1016/S1470-2045(25)00189-5. Epub 2025 May 26.
- Morris MJ, Castellano D, Herrmann K, de Bono JS, Shore ND, Chi KN, Crosby M, Piulats JM, Flechon A, Wei XX, Mahammedi H, Roubaud G, Studentova H, Nagarajah J, Mellado B, Montesa-Pino A, Kpamegan E, Ghebremariam S, Kreisl TN, Wilke C, Lehnhoff K, Sartor O, Fizazi K; PSMAfore Investigators. 177Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor therapy for taxane-naive patients with progressive metastatic castration-resistant prostate cancer (PSMAfore): a phase 3, randomised, controlled trial. Lancet. 2024 Sep 28;404(10459):1227-1239. doi: 10.1016/S0140-6736(24)01653-2. Epub 2024 Sep 15.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | 177Lu-PSMA-617 | Other / unclassified | 7400 mbq | Intravenous |
| Comparator | Abiraterone acetate | Small molecule | — | Oral |
| Comparator | Enzalutamide | Other / unclassified | — | Oral |