Study evaluating metastatic castrate resistant prostate cancer (mCRPC) treatment using <sup>177</sup>Lu-PNT2002 PSMA therapy after second-line hormonal treatment (SPLASH).
Kim N., Ur Metser, Johannes Czernin, Jérémie Calais, Vikas Prasad, Matthias Eiber, Neal D. Shore, Jessica Jensen, Neil Fleshner, Scott T. Tagawa, Oliver Sartor
Abstract
TPS5087 Background: Treatment options with minimal toxicity and novel mechanisms of action are urgently needed to improve clinical outcomes from mCRPC. Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) represents a new treatment for patients with PSMA-avid mCRPC. 177 Lu-PNT2002 (also known as [Lu-177]-PSMA-I&T) is a PSMA-targeting agent and studies have shown demonstrable promising initial data. This trial seeks to prospectively evaluate the efficacy of 177 Lu-PNT2002 for men with progressive mCRPC after androgen receptor axis-targeted (ARAT) therapy. Methods: This is a multi-center, open-label, phase III study. All patients must be at least 18 years of age, have documented progressive mCRPC at time of screening, high PSMA expression by PSMA PET/CT per blinded independent central review (BICR), chemotherapy naïve for CRPC and unfit or unwilling to receive chemotherapy. The study will commence with a 25-patient dosimetry lead-in. In the dosimetry phase, patients will receive up to four cycles of 177 Lu-PNT2002 at 6.8 GBq every 8 weeks. In the randomization phase, approximately 390 patients will be randomized in a 2:1 ratio to receive 177 Lu-PNT2002 (Arm A) versus enzalutamide or abiraterone (with prednisone or dexamethasone) (Arm B). Patients randomized to Arm B have an option to crossover to 177 Lu-PNT2002 treatment after BICR-assessed radiologic progression. The primary endpoint is Radiological progression-free survival (rPFS) assessed by BICR using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (soft tissue) and Prostate Cancer Working Group 3 (PCWG3) (bone) criteria. Key secondary endpoints include objective response rate, duration of response, PSA response, and overall survival. The study is powered at 90% to test the alternative hypothesis of a hazard ratio (HR) ≤ 0.66 at an α of 0.025. ClinicalTrials.gov identifier: NCT04647526. Clinical trial information: NCT04647526.