Randomized Multicenter Open-Label Trial Of Gt0918 (Proxalutamide) In Patients With Mcrpc That Progressed On Abiraterone Or Enzalutamide.

e17578 Background: Both abiraterone and enzalutamide have been approved for the treatment of mCRPC. GT0918 (proxalutamide) is a novel second-generation androgen receptor (AR) antagonist binding directly to the androgen receptor, impairing nuclear translocation and decreasing AR protein expression. This phase II portion of the Ph I/II study is being conducted to further evaluate safety and tolerability of GT0918 at 400 mg or 500 mg daily dosing. Methods: All eligible mCRPC pts with progressive disease based on rising prostate-specific antigen (PSA) or/and imaging while on either abiraterone or enzalutamide, but not both. One line of prior chemotherapy was allowed. Pts (n = 60) will be randomized to GT0918 either 400 mg or 500 mg po once daily for 6 months. The primary endpoint is safety and tolerability. Secondary endpoints are PSA reduction at 12 weeks, % radiographic progression at 6-month, time to imaging progression, and exploratory biomarker CTC & cf-DNA/RNA. PSA is assessed every 4 wks and tumor imaging is done every 12 wks. Results: 56 pts were screened June 2019 to January 15, 2020 and 40 pts were randomized to receive GT0918 either 400 mg or 500 mg po daily. 22 pts (55%) had enzalutamide as prior therapy and 18 pts (45%) had abiraterone as prior therapy. 17 pts (43%) had one or more lines of chemotherapy. The median age was 72 years (range 53-89) and median baseline PSA was 162 ng/mL (0.3-4195). 10 pts had 1 cycle or less of study drug due to rapid PSA progression, AEs and/or withdrawal of consent. The most common treatment-related AEs were fatigue (48%), loss of appetite/anorexia (25%), nausea (20%), lower leg extremity edema (18%), constipation (15%), weight loss (13%), vomiting (10%), and headache (8%). 8 pts (6 in 500 mg vs. 2 in 400 mg) required dose reduction due to AE. No seizures have been observed. As Jan 30, 2020, 3 pts (8%) and 8 pts (20%) had PSA reduction at 12 weeks and 4 weeks, respectively, but no 50% PSA reduction was observed. 2 pts (5%) received study drug treatment over 24 weeks and 10 pts (25%) received study drug over 16 weeks based on stable disease (SD) on imaging. Conclusions: GT0918 administrated orally once a day is well tolerated and first 40-pts taking GT0918 show some anti-tumor activities. Dose of 400 mg po daily is recommended for GT 0918 for further clinical trials. Clinical trial information: NCT03899467 .