HRS-4357, a Novel PSMA-targeted Radiologand Therapy Phase 3 Trial

HRS-4357, a novel PSMA-targeted radiopharmaceutical, is poised to enter a landmark Phase III clinical trial targeting metastatic castration-resistant prostate cancer (mCRPC). The trial, received approval from China’s National Medical Products Administration on December 23, 2025, and plans to enroll 370 patients across multiple centers in China.
This randomized, open-label, controlled study will directly compare HRS-4357 to standard androgen receptor pathway inhibitors like enzalutamide or abiraterone in patients who have progressed after exactly one prior ARPI therapy and exhibit PSMA-positive disease confirmed by PET/CT imaging. Patients must have no PSMA-negative lesions, ensuring a molecularly homogeneous population ideal for radioligand therapy evaluation. The primary endpoint is radiographic progression-free survival (rPFS) assessed by a blinded independent review committee using RECIST v1.1 criteria, with secondary endpoints including overall survival, PSA50 response rate, quality of life measures like FACT-P and EQ-5D-5L, and time to symptomatic skeletal events.

HRS-4357 represents China’s push into precision nuclear medicine, following the global success of Lu-177-PSMA-617 (Pluvicto), which demonstrated rPFS and OS benefits in similar populations. While Phase I/II data from the previous trial remain unpublished, the rapid progression to Phase III reflects strategic prioritization of radiopharmaceutical innovation and domestic Lu-177 production capacity.

The trial’s design addresses a critical sequencing question: can PSMA-targeted therapy outperform ARPI switching post-ARPI failure? Positive results could position HRS-4357 as a cost-competitive alternative to imported radioligands, expanding access in Asia and emerging markets while validating China’s radiopharmaceutical innovation ecosystem.

Clinical trial.