China-based Adagene has entered into a clinical trial collaboration with US firm Incyte to evaluate a novel immuno-oncology (IO) combination therapy for microsatellite stable colorectal cancer (MSS CRC). The study will combine Adagene's masked CTLA-4 SAFEbody antibody, muzastotug (ADG126), with Incyte's TGFβR2×PD-1 bispecific antibody (BsAb), INCA33890, in patients with or without liver metastases. The trial will be funded and conducted by Incyte, with Adagene supplying the investigational drug, muzastotug. The initial dose-escalation phase will assess safety, followed by an efficacy expansion in later-line MSS CRC patients.

Both assets have shown promise as monotherapies. Muzastotug, combined with pembrolizumab, has demonstrated encouraging response rates in a Phase Ib/II trial for MSS CRC. INCA33890 has shown clinical activity in both checkpoint-sensitive and insensitive tumours, including MSS CRC, and is already in a separate Phase III trial in the first-line setting. The collaboration aims to address a high unmet need, as MSS CRC is generally unresponsive to current anti-PD-1/PD-L1 therapies.

PharmCube's TrialiCube™ database shows that this will be the first study to investigate a combination targeting CTLA-4, PD-1/L1,  and the TGFβ pathway. Click here to request a free trial for TrialiCube™.