Phase 1 Trial of ACE723, A Dual-Payload Antibody Drug Conjugate, in Patients With Advanced HCC Who Have Failed or Progressed on Standard Systemic Therapy Containing ICIs

ACE723 is a dual-payload antibody drug conjugate targeting glypican-3 (GPC-3) that is under investigation for the treatment of unresectable or metastatic hepatocellular carcinoma (HCC).

Inclusion Criteria: * Males or females aged 18 to 75 years * HCC that is unresectable or metastatic * Pathologically confirmed HCC * Barcelona Clinic Liver Cancer (BCLC) stage B or C * Presence of at least 1 measurable lesion per RECIST 1.1 * ECOG Performance Score of 0 or 1 * Life expectancy of at least 3 months for the dose escalation portion and of at least 6 months for the dose expansion portion * Adequate bone marrow reserve * Adequate renal function * Adequate hepatic function * Left ventricular ejection fraction (LVEF) ≥50% * Ability to fully understand the investigational nature of this study * Agreement to contraception requirements Exclusion Criteria: * Other types of hepatic malignancies, such as mixed cholangiocarcinoma/HCC, sarcomatoid HCC, or fibrolamellar HCC, * History of another malignancy within the past 5 years * Ascites that requires non-pharmacologic intervention (e.g., paracentesis) * History of hepatic encephalopathy within 12 months * History of (non-infectious) ILD/pneumonitis * History of severe allergic or anaphylactic reactions to humanized monoclonal antibodies or known sensitivity or allergy to any components of ACE723. * History of bleeding events (including hematemesis or melena) * Active CNS metastases * Unresolved toxicities from prior anticancer therapy * Clinically significant active infection * Active syphilis infection and HIV infection * Pregnancy or breast-feeding women * Uncontrolled intercurrent illness * History of known substance abuse or illicit drug use * Poor compliance