Phase 2 denikitug (GS-1811) trial tests CCR8-targeted Treg-depleting antibody in MSS CRC.

This Phase 2, open-label, multicenter, randomized study from Gilead Sciences evaluates denikitug (GS-1811), a CCR8-directed monoclonal antibody designed to target CCR8-expressing tumor-infiltrating regulatory T cells (a strategy intended to reduce local immune suppression). Participants have unresectable locally advanced/recurrent or metastatic microsatellite-stable (MSS) / pMMR colorectal cancer in the third line or later setting, where checkpoint inhibitors alone usually have low activity and most patients cycle through later-line systemic options such as trifluridine-tipiracil (Lonsurf; Taiho) and regorafenib, often with bevacizumab (Avastin; Genentech/Roche) added to improve outcomes. Arms include denikitug monotherapy; denikitug + nivolumab (Opdivo; Bristol Myers Squibb), a PD-1 antibody intended to restore effector T-cell function; and denikitug + trifluridine-tipiracil (oral DNA synthesis inhibitor combination) + bevacizumab (VEGF antibody) after a safety run-in, versus the control of trifluridine-tipiracil + bevacizumab alone. The primary endpoint is investigator-assessed objective response rate per RECIST 1.1, making the key commercial/scientific question whether CCR8-directed immune remodeling can “convert” immunologically cold MSS CRC into a setting where PD-1 therapy and/or chemo-anti-VEGF backbones yield more meaningful tumor shrinkage.