A phase 1, first-in-human, multicenter study of ZW251, a novel glypican-3 (GPC3)–targeted antibody-drug conjugate (ADC), in participants with hepatocellular carcinoma (HCC).

TPS608 Background: GPC3 is highly expressed in HCC and in select solid tumors, with limited expression in normal tissues, making it an attractive therapeutic target. ZW251 is a novel GPC3-targeted ADC composed of a humanized IgG1 antibody covalently linked to ZD06519, a camptothecin derivative topoisomerase-I inhibitor. Preclinical studies demonstrated potent in vivo antitumor activity against a broad panel of HCC xenograft models, with a wide range of GPC3 expressions. ZW251 exhibits a favorable pharmacokinetic (PK) profile, and is well tolerated in non-human primates, suggesting a favorable hepatic safety profile in the setting of concurrent underlying liver dysfunction. Methods: This global, open-label, two-part phase 1 study, (dose escalation [Part 1] and dose optimization [Part 2]) will enroll approximately 100 participants. The study is enrolling adult participants (≥18 years) and adolescents (≥12 to