SAN DIEGO, California, United States, and SUZHOU, China — October 28, 2026
Adagene Inc., a clinical-stage biotechnology company developing antibody-based cancer immunotherapies, announced that the first patient has been dosed in a Phase 1 clinical study evaluating muzastotug in combination with INCA33890, a TGFβR2 × PD-1 bispecific antibody developed by Incyte. The open-label study will evaluate the combination in patients with third-line microsatellite-stable colorectal cancer (MSS CRC), including those with and without liver metastases whose disease has progressed following previous therapies. Muzastotug, also known as ADG126, is an investigational masked anti-CTLA-4 SAFEbody designed to target regulatory T cells within the tumor microenvironment. INCA33890 targets TGFβR2 and PD-1 pathways involved in suppressing antitumor immune responses. The trial will use dose escalation and expansion to investigate the combination’s safety, tolerability and potential antitumor activity. Under a collaboration announced in April 2026, Incyte is sponsoring and conducting the study, while Adagene is supplying clinical-grade muzastotug.
Phase 1 Trial Targets an Unmet Need in MSS Colorectal Cancer
Microsatellite-stable colorectal cancer represents a challenging treatment setting, as many patients respond poorly to existing immune checkpoint inhibitor approaches. The Phase 1 study will investigate whether combining muzastotug with INCA33890 can produce more durable or deeper antitumor responses in patients whose cancer has progressed after prior treatment. The trial specifically includes patients with and without liver metastases, allowing researchers to evaluate the combination across these clinically distinct groups. Liver metastases are an important consideration in metastatic colorectal cancer because the liver tumor environment can influence immune activity and treatment response. The dose-escalation and expansion design will allow investigators to assess the combination at different dose levels and further characterize its clinical profile. The study is at an early stage, and its results will be needed to determine whether the combination offers meaningful benefits and an acceptable safety profile.
Muzastotug and INCA33890 Combine Complementary Immune Mechanisms
Muzastotug is designed to use Adagene’s SAFEbody® precision-masking technology to limit antibody activity outside the tumor and enable targeting within the tumor microenvironment. Its anti-CTLA-4 mechanism is intended to deplete regulatory T cells, which can suppress immune responses against cancer. INCA33890 is a bispecific antibody targeting TGFβR2 and PD-1, two pathways associated with the suppression of T-cell function. By combining these approaches, the researchers aim to reduce immune suppression while supporting the activity of tumor-fighting T cells. Adagene Chairman and President of R&D Peter Luo said the study builds on clinical activity observed with muzastotug plus pembrolizumab and will assess whether the new combination can deepen and sustain responses in MSS colorectal cancer, including in patients with liver metastases. However, the effectiveness of this particular combination has not yet been established, and the clinical trial will need to assess whether its proposed complementary mechanisms translate into patient benefit.
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SAFEbody Platform Supports Adagene’s Broader Immunotherapy Strategy
Adagene’s Dynamic Precision Library platform includes NEObody™, SAFEbody and POWERbody™ technologies, which support the discovery and development of differentiated antibody-based therapies. SAFEbody is designed to mask an antibody’s binding domain until activation in the tumor microenvironment, with the goal of improving tumor selectivity and reducing on-target effects in healthy tissues. Muzastotug is Adagene’s lead clinical program and has received U.S. Food and Drug Administration Fast Track designation. The candidate is also being investigated in clinical studies alongside anti-PD-1 therapy, particularly for MSS metastatic colorectal cancer. Adagene aims to develop the platform across multiple antibody-based modalities, including Fc-enhanced antibodies, antibody-drug conjugates and bispecific or multispecific T-cell engagers. The new collaboration with Incyte expands the clinical evaluation of muzastotug in combination with another immune-targeting approach. Future clinical data will be important to establish the safety, optimal dosing and potential efficacy of this combination and clarify its role in treating patients with advanced colorectal cancer.
Source:Adagene Press release
