Anbogen, a Taiwan-based biotech startup, and BeiGene, a China-based biopharmaceutical company, have entered into a drug supply collaboration to evaluate the combination of Anbogen's HDAC inhibitor, ABT-301, with BeiGene's anti-PD-1 antibody, tislelizumab, in a global Phase II trial for patients with mismatch repair–proficient (pMMR) or microsatellite stable (MSS) metastatic colorectal cancer (mCRC). BeiGene will supply tislelizumab to Anbogen for the study.
Unmet Need in MSS mCRC
Globally, over 1.9 million new cases of colorectal cancer were diagnosed in 2020. Immune checkpoint inhibitors (ICIs) are a primary treatment for mCRC with mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H). However, less than 5% of mCRC cases exhibit dMMR/MSI-H, leaving a significant unmet need for the 95% of patients with pMMR/MSS tumors who do not respond to ICIs. This collaboration aims to address this therapeutic gap.
ABT-301: Enhancing ICI Efficacy
ABT-301, a novel HDAC inhibitor, has demonstrated promising safety and pharmacokinetic profiles in a Phase 1 study as a single agent. Preclinical studies suggest that ABT-301 enhances the effectiveness of anti-PD-1/anti-PD-L1 therapies by increasing CD8+ cytotoxic T cells and decreasing monocytic myeloid-derived suppressor cells within the tumor and circulation, and inhibiting angiogenesis. These immune response enhancements may broaden the efficacy of ICIs in colorectal cancer patients.
Phase II Trial Design
The upcoming Phase II study will investigate the effectiveness of treatment regimens combining ABT-301 and tislelizumab, with and without Bevacizumab, in pMMR/MSS mCRC patients. The clinical trial will be conducted in multiple centers and will evaluate the safety, tolerability, and preliminary efficacy of the combination therapy in patients with advanced MSS CRC. Enrollment is expected to begin in the first quarter of 2025.
