China-based Akeso (HKEX: 9926) has received clearance from China's National Medical Products Administration (NMPA) to initiate a Phase I study of AK157D1, a B7-H3-targeting antibody-drug conjugate (ADC), in patients with advanced solid tumors. The clearance makes AK157D1 the third ADC from Akeso's internal platform to enter clinical development.
AK157D1 combines a humanized B7-H3 antibody with a DXd topoisomerase I inhibitor payload using Akeso's site-specific conjugation and MC-AAA linker technology. B7-H3 is highly expressed across multiple solid tumors, including lung, prostate, esophageal, colorectal, and breast cancers, while showing more limited expression in normal tissues, making it an increasingly competitive ADC target.
Akeso said AK157D1 demonstrated antitumor activity across multiple preclinical tumor models and was designed to improve the therapeutic window associated with B7-H3-directed ADCs. The company specifically highlighted hematologic toxicity and interstitial lung disease as safety issues it aims to mitigate through the molecule's antibody, linker, and conjugation design. Whether those characteristics translate into clinical differentiation will be a key focus of the Phase I study.
Akeso also plans to evaluate AK157D1 in combination with its approved bispecific antibodies, including ivonescimab, its PD-1/VEGF bispecific currently under US FDA review for EGFR-mutant non-small cell lung cancer, and cadonilimab (Caitanni), a PD-1/CTLA-4 bispecific approved for multiple indications in China.