Adagene Inc. is advancing its innovative immunotherapy program with a new Phase 2 neoadjuvant trial of ADG126 (muzastotug) in patients with stage II or III colorectal cancer, marking a significant step toward earlier-stage treatment with immune checkpoint inhibition.
Study Design and Objectives
The investigator-initiated trial (NCT06846268), led by Dr. Yong Wei Peng from the National University Cancer Institute, Singapore, will evaluate high doses of ADG126 in combination with KEYTRUDA® (pembrolizumab) before surgery. The study's primary endpoint focuses on Major Pathologic Response (MPR), defined as ≤10% residual viable tumor in the surgical specimen.
Secondary endpoints encompass complete pathological response, disease-free survival, and safety assessments. The trial will also investigate the pharmacodynamic effects of the combination therapy on the tumor microenvironment's immune profile and analyze ADG126's pharmacokinetic characteristics in tumor tissues.
Innovative Technology Platform
ADG126 represents a breakthrough in antibody engineering through Adagene's SAFEbody® technology platform. This masked anti-CTLA-4 antibody specifically targets regulatory T cells within the tumor microenvironment while minimizing off-tumor toxicity in healthy tissues - a common challenge with traditional CTLA-4 inhibitors.
The therapy's design leverages precision masking technology to shield the binding domain until activated within the tumor microenvironment, potentially offering an improved safety profile compared to existing treatments.
Clinical Rationale and Potential Impact
"The foundation for this neoadjuvant study is supported by the compelling combination efficacy and safety profile of ADG126 with pembrolizumab in late-stage MSS CRC patients," explained Peter Luo, Chairman, CEO, and President of R&D at Adagene. "We believe that advancing immunotherapy into the curative neoadjuvant setting holds significant promise."
The combination approach aims to enhance anti-tumor immunity through dual mechanisms: CTLA-4-mediated T regulatory cell depletion and PD-1 blockade to reinvigorate exhausted T cells. This strategy could potentially provide patients with early-stage colorectal cancer a more effective treatment option before surgery.
Development Timeline
The trial is scheduled to begin enrollment in April 2025, with primary completion expected by mid-2027. Up to 20 patients will be recruited to evaluate the therapy's efficacy in the neoadjuvant setting, potentially opening new avenues for immunotherapy in early-stage colorectal cancer treatment.
