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).