Highlights

  • HUTCHMED has initiated a global Phase I trial for ATTC candidate HMPL-A251.
  • The first patient was dosed in China, with study sites also active in the US.
  • The program evaluates safety, dosing, and early activity in HER2-expressing solid tumors.

HUTCHMED (China) Limited (NASDAQ:HCM) has announced the start of its global Phase I clinical development program for HMPL-A251, an antibody-targeted therapy conjugate (ATTC). The first patient received the initial dose on December 16, 2025, in China. The study is being conducted across multiple sites in China and the United States, reflecting a coordinated clinical development approach.

Study Design and Patient Population
The ongoing study is a first-in-human, open-label, multicenter Phase I/IIa trial evaluating HMPL-A251 as a monotherapy. It is enrolling adult patients with unresectable, advanced, or metastatic solid tumors that express HER2. The trial is structured in two sequential components to support dose evaluation and further clinical assessment.

The Phase I portion focuses on dose escalation to assess safety and tolerability while identifying the maximum tolerated dose (MTD) and recommended dose for expansion (RDE). The subsequent Phase IIa portion includes dose expansion and optimization to further evaluate safety and preliminary efficacy and to determine the recommended dose for later-stage development, including the recommended Phase II dose (RP2D) or Phase III dose (RP3D).

Endpoints and Evaluation Criteria
Primary outcome measures in the Phase I stage include safety and tolerability parameters, along with dose-limiting toxicities. In the Phase IIa stage, the study continues safety evaluations while also assessing preliminary signals of antitumor activity at selected dose levels.

Secondary outcome measures include pharmacokinetic profiling and immunogenicity assessments, as well as additional analyses of early antitumor effects. Full study details are available on clinicaltrials.gov under the identifier NCT07228247.

ATTC Platform and Candidate Profile
HMPL-A251 consists of a humanized anti-HER2 IgG1 antibody conjugated through a cleavable linker to a selective PI3K/PIKK inhibitor payload. The ATTC platform combines targeted antibody delivery with small-molecule pathway inhibition, differing from cytotoxin-based antibody-drug conjugates.

Preclinical findings related to HMPL-A251 were presented at the 2025 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. These data supported advancement into clinical testing and informed the current global development program.

Share Price Snapshot
HCM closed at USD 13.19 on 16 December 2025, down 1.05% from the previous session. The stock opened at USD 13.44, reaching a high of USD 13.44 and a low of USD 13.06 during the day.