SAN DIEGO and SUZHOU, China — September 22, 2026
Adagene announced that China’s National Medical Products Administration (NMPA) has approved the investigational new drug application for ADG138, a double-masked HER2×CD3 bispecific T-cell engager designed using the company’s proprietary SAFEbody® precision masking technology. Adagene expects to initiate a first-in-human Phase 1 study in patients with advanced solid tumors in the fourth quarter of 2026. The program is designed to evaluate a tumor-selective T-cell engagement approach intended to limit systemic toxicity associated with conventional T-cell engagers.
ADG138 Advances Into Phase 1 Clinical Development
The planned Phase 1 study is an open-label, first-in-human clinical trial evaluating the safety and preliminary efficacy of ADG138 in patients with advanced solid tumors. The study will also assess dosing and is intended to determine the recommended dose for subsequent Phase 2 development. ADG138 is designed to simultaneously target HER2 on tumor cells and CD3 on T cells, while masking both binding sites until the molecule reaches the tumor microenvironment. Adagene expects this design to enable activation within tumors and selective engagement of T cells against HER2-expressing cancer cells.
SAFEbody Technology Enables Double-Masked Design
ADG138 uses Adagene’s SAFEbody® precision masking technology to covalently link masking peptides to both the HER2- and CD3-binding arms of the molecule. In its inactive state, the candidate is designed to reduce binding to HER2-expressing cells and T cells, with activation occurring within the tumor microenvironment. Preclinical studies presented at the 2022 AACR Annual Meeting reported approximately 220-fold and greater than 1,000-fold reductions in HER2 and CD3 binding, respectively, while maintaining T-cell-mediated tumor cell killing. ADG138 also demonstrated tumor regression in HER2-high and HER2-low models, including a model reported to be refractory or resistant to Enhertu.
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Preclinical Data Support Further ADG138 Evaluation
Preclinical studies showed ADG138 activity in Enhertu-resistant models and synergistic antitumor effects when combined with anti-CTLA-4, anti-PD-1 or anti-CD137 antibodies. Adagene also reported substantially reduced cytokine release and tolerability at doses more than 300-fold higher than an unmasked T-cell engager in preclinical testing, along with a longer apparent half-life and higher systemic exposure than the parental molecule. These findings are preclinical and will require clinical validation. The ADG138 program expands Adagene’s application of SAFEbody technology to T-cell engagers, complementing the company’s clinical-stage muzastotug (ADG126) program targeting CTLA-4.
Source :Adagene, press release
