Study of TVB-2640 in Men With Metastatic Castration-Resistant Prostate Cancer

This phase I, open-label, dose-escalation study is designed to evaluate the dose limiting toxicities (DLTs) and maximum-tolerated dose (MTD) of TVB-2640 plus Enzalutamide and establish the TVB-2640 dose recommended for further investigation in phase 2 (i.e., recommended phase 2 dose \[RP2D\]). Patients with a confirmed histological or cytological diagnosis of prostate cancer (PC), evidence of metastatic PC on imaging (bone scan and/or CT/MRI scan), serum testosterone \<50 ng/dl, who had progressed on androgen-depletion therapy (ADT), with documented progressive metastatic castration-resistant prostate cancer (mCRPC) based on Prostate Cancer Working Group 3 (PCWG3) criteria and no previously treatment with cytotoxic chemotherapy are eligible. This study represents the first clinical evaluation of TVB-2640 in combination with Enzalutamide. All patients will receive Enzalutamide monotherapy at the approved dose of 160 mg once daily for 28 days to reach the steady state as determined by measuring Enzalutamide and des-methyl-Enzalutamide levels. Participants who complete the Enzalutamide run-in period will begin oral TVB-2640 at the dose of 100 mg. The dose escalation scheme will be the Bayesian optimal interval (BOIN) design with additional dose levels of 100 mg, 150mg, 200 mg, 250 mg, and 300mg daily. The maximum sample size for the phase I will be 30 patients and the target DLT rate is 25% or less and a maximum of 9 patients at any dose level.