China’s National Medical Products Administration has approved an investigational new drug application for Adagene’s ADG138, a double-masked HER2×CD3 bispecific T-cell engager targeting advanced solid tumors.
The clearance permits an open-label clinical study to evaluate safety and preliminary efficacy in patients with advanced solid tumors and to establish the recommended dose for a Phase 2 trial.
Adagene plans to initiate the Phase 1 study in the fourth quarter of 2026, the company said.
ADG138 leverages Adagene’s SAFEbody precision masking technology, which applies masking peptides to both the HER2 and CD3 binding sites to keep the molecule inactive until it reaches the tumor microenvironment, reducing off-target engagement.
Preclinical data presented at the American Association for Cancer Research Annual Meeting in 2022 showed the candidate achieved approximately 220-fold and greater than 1,000-fold reductions in binding to HER2 and CD3, respectively, compared with an unmasked version. ADG138 was tolerated at doses over 300-fold higher than an unmasked T-cell engager, the company noted.
In tumor models, ADG138 drove regression in both HER2-high and HER2-low cancers, including a model refractory or resistant to Enhertu (DS-8201). The candidate also demonstrated synergistic anti-tumor activity when combined with anti-CTLA-4, anti-PD-1, or anti-CD137 antibodies, alongside reduced cytokine release and a longer apparent half-life relative to its parental molecule.
The approval advances Adagene’s bispecific pipeline as it continues development of its lead candidate muzastotug (ADG126), currently in Phase 1b/2 and Phase 2 studies in combination with anti-PD-1 therapy for microsatellite stable metastatic colorectal cancer. Shares of Adagene, listed on NASDAQ under ADAG, will be watched for investor reaction to the China filing milestone.
