HUTCHMED Begins Global Clinical Development Of ATTC Candidate HMPL-A251 For Patients With Solid Tumors

HUTCHMED (China) Limited has announced the start of its global Phase I clinical development program for HMPL-A251, a first-in-class antibody-targeted therapy conjugate designed for the treatment of HER2-expressing cancers. HMPL-A251 combines a highly selective and potent PI3K/PIKK inhibitor with a humanized anti-HER2 IgG1 antibody, linked through a cleavable linker that allows the drug payload to be released inside tumor cells. Clinical study sites are located in both the United States and China, and the first patient received the initial dose on December 16, 2025, in China.

The first-in-human Phase I/IIa study is an open-label, multicenter trial evaluating HMPL-A251 as a single-agent treatment in adult patients with unresectable, advanced, or metastatic solid tumors that express HER2. The study is structured in two stages. The Phase I portion focuses on dose escalation to evaluate safety and tolerability and to identify the maximum tolerated dose and recommended doses for expansion. The Phase IIa portion is designed to expand and optimize dosing, further assess safety, and evaluate early signs of efficacy. This phase will also help determine the recommended dose for later-stage Phase II or Phase III studies.

In addition to safety and dosing, the study will assess several secondary outcomes, including preliminary antitumor activity, how the drug behaves in the body over time, and whether it triggers an immune response. Further details about the trial are available on clinicaltrials.gov under the identifier NCT07228247. HMPL-A251 is the first drug candidate to enter clinical development from HUTCHMED’s next-generation antibody-targeted therapy conjugate platform. The initial set of programs using this platform is built around a highly potent and selective PI3K/PIKK inhibitor payload. 

By attaching this payload to an anti-HER2 antibody, the therapy is designed to deliver targeted inhibition directly into HER2-expressing cancer cells. This strategy aims to reduce the systemic toxicity and limited therapeutic window that have historically challenged PI3K/PIKK inhibitor therapies, while enabling stronger and more sustained inhibition of cancer-driving pathways.

Preclinical research supporting HMPL-A251 was presented at the 2025 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. These data highlight the potential of the antibody-targeted therapy conjugate platform, support the global clinical evaluation of HMPL-A251, and demonstrate the broader promise of HUTCHMED’s PI3K/PIKK inhibitor linker-payload technology as the foundation for a future pipeline of targeted cancer therapies.