2427 - The Extended/Phase II Study of Safety And Tolerability Of Proxalutamide (GT0918) In Subjects With Metastatic Castrate Resistant Prostate Cancer (mCRPC) Who Failed Either Abiraterone (Abi) Or Enzalutamide (Enza)

Background

Prostate cancer is the most common malignant tumor in men and is the second leading cause of cancer-related deaths in men. Recently there are several 2^nd generations of anti-androgen therapies approved and used widely in clinics. However, many patients (pts) relapse after a period of treatment in clinic due to various resistant mechanisms and require new drug or additional therapy. GT0918 is a new chemical entity of androgen receptor (AR) antagonist with more specificity and activity in inhibiting ARs with reduced drug accumulation in the CNS and also show activities on AR mutations including ART878A leading AR drug resistance in cell assays. In early phase I clinical trial of dose escalation study (NCT02826772), GT0918 was shown well tolerated in mCRPC pts progressed lines of standard and experimental therapies with some durable responses. 400mg and 500mg orally once daily were selected warranted for further clinical testing.

Trial design

The study is an open-label, randomized, multicenter, trial to assess GT0918 in mCRPC pts progressed after either abi or enza. The primary object is to evaluate the safety and tolerability of GT0918 either 400 mg or 500 mg daily dose to determine the RP2D for Ph III and/or other confirming studies. The secondary objectives are to evaluate efficacy endpoints including≥ 50% PSA suppression, the percentage of radiographic disease progression, the time to radiographic and bone progression, the time to PSA progression. The key eligibility includes histologically confirmed mCRPC, prior failed therapy either abi or enza (only 1 prior chemotherapy is allowed), progression defined by PCWG 3 criteria, and life expectancy of ≥ 6 months (at screening). 60 pts are enrolled at 12 US sites and randomized in a 1:1 ratio to orally take 400 mg or 500 mg of GT0918 once daily for initial treatment of 6 months. Pts will continue treatment with GT0918 up to 12 months at their assigned dose until disease progression, intolerable toxicities (AEs), or withdrawn consent. The trial started in May 2019. An interim analysis of both safety and efficacy will be performed after 30 pts become evaluable.

Clinical trial identification

NCT03899467 (April 2, 2019).

Editorial acknowledgement

Legal entity responsible for the study

Suzhou Kintor Pharmaceuticals Inc.

Funding

Suzhou Kintor Pharmaceuticals Inc.

Disclosure

N.J. Vogelzang: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Janssen; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Bayer. P. Zhang: Full / Part-time employment: Suzhou Kintor Pharmaceuticals Inc. K. Zhou: Full / Part-time employment: Suzhou Kintor Pharmaceuticals Inc. All other authors have declared no conflicts of interest.