San Diego, USA & Suzhou, China, April 2, 2026
Breakthrough Collaboration in Immuno-Oncology
In a significant step forward for cancer immunotherapy, Adagene Inc. and Incyte have announced a strategic clinical collaboration to evaluate a novel combination therapy targeting microsatellite stable colorectal cancer (MSS CRC)—a subtype historically resistant to immunotherapy. The partnership will assess muzastotug (ADG126), Adagene’s masked anti-CTLA-4 SAFEbody®, in combination with Incyte’s TGFβR2 × PD-1 bispecific antibody (INCA33890). The planned Phase 1 clinical study, expected to begin in 2026, will focus on third-line (3L) MSS CRC patients, including those with and without liver metastases, a population with particularly poor prognosis. This collaboration highlights the growing importance of combination immunotherapies in overcoming resistance mechanisms and improving patient outcomes in difficult-to-treat cancers.
Promising Mechanisms and Clinical Potential
The scientific rationale behind this collaboration lies in combining complementary immune-modulating mechanisms to enhance anti-tumor responses. Muzastotug, designed using Adagene’s SAFEbody® precision masking technology, selectively activates within the tumor microenvironment, thereby improving safety and tolerability while maintaining efficacy. Previous studies have shown encouraging response rates and durable outcomes when muzastotug was combined with pembrolizumab (KEYTRUDA®) in MSS CRC patients. Meanwhile, INCA33890 has demonstrated promising clinical efficacy and safety as a monotherapy across both immune checkpoint–sensitive and resistant tumors, including MSS CRC.
The combination aims to overcome the limitations of traditional PD-1/PD-L1 therapies, which have shown limited effectiveness in MSS CRC due to its immune-resistant tumor biology. By integrating CTLA-4 inhibition with TGF-β pathway modulation and PD-1 targeting, the study seeks to unlock synergistic immune activation, potentially leading to improved tumor regression and survival outcomes.
Advertisement
Study Design and Strategic Impact
The upcoming trial will be sponsored and conducted by Incyte, with Adagene supplying clinical-grade muzastotug. The study will begin with a dose-escalation phase to evaluate safety and tolerability, followed by an expansion cohort to assess clinical efficacy in chemotherapy-refractory MSS CRC patients. Importantly, this collaboration reinforces muzastotug’s positioning as a potential “backbone therapy” for next-generation immuno-oncology combinations. Adagene’s leadership emphasized that this marks the second major validation of its SAFEbody® platform when paired with advanced PD-1–based bispecific antibodies, further strengthening its role in precision oncology innovation.
Additionally, Incyte’s broader clinical strategy includes a Phase 3 trial evaluating INCA33890 in combination with standard chemotherapy regimens, signaling strong confidence in its therapeutic potential. For patients with MSS CRC—who represent the majority of colorectal cancer cases and have limited treatment options—this collaboration could represent a transformative advancement in care.
Future Outlook for MSS CRC Treatment
This collaboration underscores a broader shift in oncology toward multi-targeted, biomarker-driven therapies that address complex tumor microenvironments. MSS CRC has long been considered a “cold tumor”, with minimal immune infiltration and poor response to checkpoint inhibitors. The integration of SAFEbody® technology, which minimizes off-target toxicity, with a bispecific antibody targeting both TGF-β and PD-1 pathways, could redefine treatment paradigms. If successful, the combination may pave the way for more effective and safer immunotherapy regimens, not only in colorectal cancer but also across other solid tumors with immune resistance profiles.
As clinical trials progress, the oncology community will closely monitor outcomes related to overall response rate, progression-free survival, and tolerability, which will be critical in determining the future role of this combination in standard treatment protocols.
Source: Adagene press release
