HUTCHMED (00013) has announced the commencement of a Phase I/IIa clinical trial for its second antibody-targeted conjugate drug candidate, HMPL-A580, in patients with unresectable advanced or metastatic solid tumors. The study is now underway in both China and the United States. The first patient received the initial dose on March 4, 2026.

HMPL-A580 is a first-in-class ATTC. It consists of a highly selective and potent small-molecule PI3K/PIKK inhibitor as the payload, which is conjugated to an anti-EGFR antibody using a cleavable linker. This candidate represents HUTCHMED's second ATTC developed using its innovative PI3K/PIKK inhibitor payload technology. EGFR is highly expressed in many solid tumors and is widely recognized as a key driver of tumorigenesis and disease progression.

Preclinical data indicate that combining PAM pathway inhibition with anti-EGFR therapy produces a synergistic effect, enhancing antitumor activity. These findings are scheduled for presentation at an upcoming academic conference.

This first-in-human trial is an open-label, multicenter study designed to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary efficacy of HMPL-A580. The trial consists of two phases. During the Phase I dose-escalation stage, patients will receive intravenous HMPL-A580 at predetermined dose levels to determine the maximum tolerated dose and the recommended dose for expansion. The subsequent Phase IIa dose expansion/optimization stage will further assess the safety, tolerability, and initial antitumor activity of HMPL-A580 in selected solid tumor types and establish the recommended dose for further development.