HUTCHMED has initiated a phase-I/II(a) clinical trial of HMPL-A580, HUTCHMED’s second novel Antibody-Targeted Therapy Conjugate (ATTC), in patients with unresectable, advanced or metastatic solid tumours in China and the US. The first patient received the first dose on 4 March, 2026. 

HMPL-A580 is a first-in-class ATTC comprising a highly selective and potent PI3K/PIKK small-molecule inhibitor payload linked to an anti-EGFR antibody via a cleavable linker, HUTCHMED’s second ATTC based on this highly novel PI3K/PIKK inhibitor payload. EGFR is highly expressed in multiple types of solid tumours and is well-recognised as a driving force in tumorigenesis and disease progression. Pre-clinical data have shown that PAM pathway inhibition synergises with anti-EGFR therapy to enhance anti-tumour activity, and will be presented at an upcoming scientific conference. 

This first-in-human phase I/II(a), multi-centre, open-label study evaluates the safety, tolerability, pharmacokinetics, immunogenicity and preliminary efficacy of HMPL-A580. The study consists of two parts. In the phase-I dose escalation part, patients will receive HMPL-A580 intravenously at pre-defined dose levels to determine the maximum tolerated dose and recommended dose for expansion. The subsequent phase-II(a) dose expansion/?optimisation part is to further characterise the safety, tolerability and preliminary anti-tumour activity of HMPL-A580 in selected solid tumours, and to determine the recommended dose for the next phase.