HUTCHMED (00013) initiates global clinical development of the ATTC candidate drug HMPL-A251 for the treatment of solid tumors.

HUTCHMED (00013) announces the initiation of the global Phase I clinical development program for HMPL-A251. HMPL-A251 is a globally pioneering PI3K/PIKK-HER2 antibody-drug conjugate (ATTC), consisting of a highly selective, potent PI3K/PIKK inhibitor as the payload and a humanized anti-HER2 IgG1 antibody linked by a cleavable linker. The study will be conducted in the United States and China. The first patient received their first dose of treatment in China on December 16, 2025. This first-in-human trial is a Phase I/IIa, open-label, multicenter clinical study aiming to evaluate HMPL-A251 as a monotherapy in adult patients with unresectable, HER2-expressing advanced or metastatic solid tumors. The study consists of two stages: a dose escalation stage in Phase I and a dose expansion and optimization stage in Phase IIa. The primary objectives of the study are the safety and tolerability of HMPL-A251, to determine the Maximum Tolerated Dose (MTD) and/or Recommended Dose Expansion (RDE) in the Phase I part, and further evaluate the safety and preliminary efficacy of RDE, as well as determine the Recommended Phase II Dose (RP2D) or Recommended Phase III Dose (RP3D) clinical trial dose in the Phase IIa part. Secondary objectives include preliminary anti-tumor activity, pharmacokinetic characteristics, and immunogenicity of HMPL-A251. HMPL-A251 is the first candidate drug under HUTCHMED's new generation ATTC platform to enter clinical development. The platform's initial candidate drugs use potent and highly selective PI3K/PIKK inhibitors as the payload. By linking this innovative payload with an anti-HER2 antibody, HMPL-A251 is designed to precisely target HER2-expressing tumor cells with the potential to overcome the long-standing limitations of systemic toxicity and narrow therapeutic window of PI3K/PIKK inhibitor drugs. This strategy aims to improve overall tolerability while achieving more effective and sustained pathway inhibition. Preclinical data of HMPL-A251 was presented at the 2025 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. These data support the transformative potential of the ATTC platform, endorse the global clinical assessment of HMPL-A251, and demonstrate the broad potential of HUTCHMED's linker-payload combinations based on PI3K/PIKK inhibitors, promising to derive a future series of ATTC candidate drugs.