Adagene and Incyte Launch Clinical Collaboration for Muzastotug Combination in Colorectal Cancer
Adagene and Incyte will collaborate on a Phase 1 study combining muzastotug with INCA33890 for MSS colorectal cancer patients, beginning in 2026. The collaboration marks the second instance where Adagene's SAFEbody technology is paired with a PD-1-based bispecific. Muzastotug has shown encouraging response rates in combination with pembrolizumab in previous trials.
Adagene has announced a clinical collaboration with Incyte to evaluate the combination of muzastotug (ADG126) and INCA33890, a TGFβR2 × PD-1 bispecific antibody, in patients with microsatellite stable colorectal cancer (MSS CRC) with or without liver metastases. The Phase 1 study is expected to begin in 2026 in third-line MSS CRC patients with and without liver metastases, with Incyte sponsoring and conducting the study while Adagene provides clinical supply of muzastotug.
Muzastotug in combination with Merck's anti-PD-1 therapy, KEYTRUDA (pembrolizumab) has demonstrated encouraging overall response rates and durable responses in a Phase 1b/2 trial in 3L MSS CRC patients. As a monotherapy, INCA33890 has demonstrated promising clinical efficacy and safety in immune checkpoint sensitive and insensitive cancers, including MSS CRC with and without liver metastases. Incyte has recently initiated a Phase 3 study evaluating bevacizumab and FOLFOX (standard of care chemotherapy) with or without INCA33890 in 700 first-line MSS CRC patients.
The planned dose escalation portion of the study will evaluate safety and tolerability, followed by an efficacy expansion cohort in patients with chemotherapy-refractory MSS CRC patients with and without liver metastases. MSS CRC is well-known to be largely non-responsive to anti-PD-1 / PD-L1 therapy. INCA33890 monotherapy has demonstrated promising initial clinical efficacy and safety in immune checkpoint sensitive/insensitive tumors, including MSS CRC with and without liver metastases.
Muzastotug, a masked anti-CTLA-4 SAFEbody with FDA Fast Track designation, is currently being evaluated in multiple ongoing studies, including a Phase 1b/2 clinical trial in combination with pembrolizumab in MSS CRC patients without liver metastases, a randomized Phase 2 study in MSS CRC patients without liver metastases designed to determine the optimal dose to advance into a Phase 3 registration trial, and a Phase 1b/2 dose escalation and expansion study of muzastotug in combination with Sanofi's SAR445877 (PD-1 x IL-15 fusion protein) in adults with advanced solid tumors.
Adagene's lead clinical program, muzastotug (ADG126), is a masked, anti-CTLA-4 SAFEbody that targets a unique epitope of CTLA-4 in regulatory T cells (Tregs) in the tumor microenvironment. Muzastotug is currently in Phase 1b/2 and Phase 2 clinical studies in combination with anti-PD-1 therapy, particularly focused on microsatellite stable (MSS) metastatic colorectal cancer (CRC).