ProSTAR: A Study Evaluating CPI-1205 in Patients With Metastatic Castration Resistant Prostate Cancer

Study CPI-1205-201 was a Phase 1b/2, multi-center, open-label study of CPI-1205 alone and with cobicistat in subjects with mCRPC in combination with either enzalutamide or abiraterone/prednisone. The study initially had two phases: a Phase 1 dose-finding, dose-escalation study intended to establish the Recommended Phase 2 Dose (RP2D) of CPI-1205 for the Phase 2 portion. The study underwent three amendments. PHASE 1b In the Phase 1b dose-escalation phase and prior to Amendment 2, subjects were enrolled into Phase 1b dose level CPI-1205 PO three times daily (TID) + enzalutamide or abiraterone/prednisone. In Amendment 2, new subjects were enrolled into cohorts including: Dose-escalating CPI-1205 PO twice daily (BID) + fixed-dose cobicistat PO BID + enzalutamide Dose-escalating CPI-1205 PO BID + fixed-dose cobicistat PO BID + abiraterone/prednisone In Amendment 3, Phase 1b expansion cohort(s) were added in the heavily pretreated population (HPEC). An HPEC began enrollment if 0 out of 3 or 1 out of 6 subjects treated with a specific regimen (i.e., CPI-1205 with or without cobicistat, in combination with enzalutamide or abiraterone) at a given dose level during Phase 1b dose escalation experienced a dose-limiting toxicity (DLT). Following determination of the maximum tolerated dose (MTD) in each of the CPI-1205 BID + cobicistat combinations (and possibly in the CPI-1205 TID combination) and after evaluation of the BID cohorts without cobicistat (if applicable), only one of the CPI-1205 dosing schedules was selected as the RP2D for each combination. One or both combinations proceeded to Phase 2 after consideration of pharmacokinetic (PK) and pharmacodynamic (PD) results, data from the HPEC(s), and safety data. PHASE 2 If only one partner product was chosen for Phase 2, the study proceeded as an open-label randomized Phase 2 trial, with subjects randomized to either the combination arm (CPI-1205 at the RP2D \[with or without cobicistat\] in combination with enzalutamide or abiraterone/prednisone) or the control arm (enzalutamide or abiraterone/prednisone as monotherapy). If both partner products were chosen, the second Phase 2 was either a second open-label randomized trial or a single-arm Phase 2 trial (following a Simon's 2-stage design). The design of the second trial was determined by the Sponsor based on preliminary efficacy and PK. CPI-1205 was administered orally TID or BID (as of Amendment 2). Cobicistat dosing began with one dose the evening prior to Day 1 of CPI-1205 and continued PO BID starting on Day 1. Enzalutamide and abiraterone were given PO once daily, and prednisone was given PO BID (or at the investigator's discretion). Successive 28-day treatment cycles were repeated without planned breaks, as long as the combination was well tolerated, until radiographic disease progression, unequivocal clinical progression, or planned initiation of another systemic treatment. Investigators could continue treatment in subjects with progression in one site if other lesions might benefit. Subjects in the control arm who progressed had the option to cross over to the combination arm, provided they met eligibility criteria.