HUTCHMED (China) Ltd. has announced the initiation of a global Phase I clinical study for HMPL-A251, a first-in-class PI3K/PIKK-HER2 Antibody-Targeted Therapy Conjugate (ATTC) for patients with solid tumors. The study, which includes sites in both the US and China, began dosing its first patient on December 16, 2025. HMPL-A251 features a selective PI3K/PIKK inhibitor payload conjugated to a humanized anti-HER2 antibody, aiming to deliver targeted pathway inhibition to HER2-expressing tumor cells. The trial consists of a Phase I dose escalation and a Phase IIa dose expansion, with primary endpoints focused on safety, tolerability, and dose determination. Preclinical data supporting HMPL-A251 were presented at the 2025 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. Further study details are available under clinicaltrials.gov identifier NCT07228247.