Multicenter phase I/II trial of BBI608 and pembrolizumab combination in patients with metastatic colorectal cancer (SCOOP Study): EPOC1503.

760Background: The anti–programmed death 1 (PD-1) antibody, pembrolizumab provided an objective response rate (ORR) of 40% in patients (pts) with Mismatch Repair–Deficient (dMMR) or Microsatellite Instability–High (MSI-H) metastatic colorectal cancer (mCRC) vs 0% in pts with MMR-proficient/Microsatellite Stable (MSS) mCRC. The WNT/β-catenin signaling has been reported to prevent anti-tumor immunity and promote resistance of anti-PD-1/PD-L1 antibodies. This study investigates efficacy and safety of the combination of BBI608, which blocks phosphorylated STAT3 and downregulates WNT/β-catenin signaling, with pembrolizumab in pts with mCRC (both MSS and MSI-H). Here, we present the results of the phase I part. Methods: Phase I part was designed to determine the recommended phase II dose (RP2D) in a “3+3” cohort-based dose escalation design of BBI608 (240mg BID every day on level 1 and 480mg BID every day on level 2) with pembrolizumab (200mg/body q3w). We also conduct biomarker research using paired samples fr...