A Study of ABT-301 Plus Tislelizumab With Bevacizumab in pMMR/Non-MSI-H Locally Advanced or mCRC

ABT-301 is an oral histone deacetylase inhibitor (HDACi) administered in capsule form once daily (QD ±3 hours) or every 12 hours (Q12H ±3 hours, with at least 9 hours between doses) with water in 21-day treatment cycles. In Part 1 (dose-escalation phase), participants receive escalating doses of ABT-301 (50 mg QD, 100 mg QD, 50 mg Q12H, 150 mg QD, or 75 mg Q12H). Tislelizumab 200 mg and bevacizumab 7.5 mg/kg will be administered through IV infusion on Day 1 of every 21-day treatment cycle. This phase aims to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of ABT-301 when combined with tislelizumab and bevacizumab. In Part 2 (dose-optimization phase), two ABT-301 doses/schedules will be selected for further evaluation of antitumor activity, safety, and tolerability in adults with pMMR/non-MSI-H colorectal cancer (CRC).

Tislelizumab is a humanized immunoglobulin G4-variant monoclonal antibody (mAb) blocking programmed cell death protein 1 (PD-1). Tislelizumab 200 mg will be administered through IV infusion on Day 1 of every 21-day treatment cycle in combination with ABT-301 and bevacizumab throughout both parts of the study.

Bevacizumab (Avastin®) is a recombinant humanized monoclonal IgG1 antibody which binds to and neutralizes VEGF. Neutralization of VEGF by bevacizumab has been shown to inhibit the VEGF-induced proliferation of human endothelial cells in vitro and to decrease micro-vessel density and interstitial pressure in tumor xenografts in vivo. Bevacizumab 7.5 mg/kg will be administered through IV infusion on Day 1 of every 21-day treatment cycle in combination with ABT-301 and tislelizumab, throughout both parts of the study.