The 2026 American Society of Clinical Oncology (ASCO) Annual Meeting will be held from May 29 to June 3 in Chicago, USA. Lepu Biopharma will present the latest data from its Phase 1/2 clinical trial of GPC3 ADC in advanced liver cancer at this conference.
The study, MRG006A-001, is a multicenter, open-label Phase 1/2 trial enrolling patients with advanced liver cancer who have failed standard of care. Only the dose-expansion cohort requires screening for GPC3 expression levels. MRG006A is administered once every three weeks, with a dose escalation range of 1.6–6.4 mg/kg. As of December 19, 2025, the trial has reached the maximum dose cohort of 6.4 mg/kg. In the Phase 1b part, three dose levels (3.2, 4.0, and 4.8 mg/kg) are selected for dose expansion. A total of 26 patients with moderate or high GPC3 expression are enrolled, with a median of 2 prior lines of therapy (range: 1–4). Among them, 25 patients (96.2%) have received prior immune checkpoint inhibitor and anti-angiogenic therapy. Among the 25 evaluable patients, the objective response rate (ORR), disease control rate (DCR), and clinical benefit rate (CBR) are 23.1%, 68.0%, and 32.0%, respectively. For the 12 patients with high GPC3 expression, the ORR, DCR, and CBR are 33.3%, 75.0%, and 50.0%, respectively; median progression-free survival (mPFS) is 7.0 months, and median duration of response (mDOR) is 4.2 months, with follow-up ongoing.
In terms of safety, the incidence of grade ≥3 treatment-emergent adverse events is 42.3%. The most common adverse events include decreased platelet count, elevated plasma bilirubin, elevated AST, decreased white blood cell count, and nausea. Overall, the treatment is well tolerated, with no treatment-related permanent discontinuations or deaths. These clinical data demonstrate that MRG006A has a manageable safety profile and shows promising efficacy in patients with advanced liver cancer who have GPC3 expression and have received extensive prior treatment.
Lepu Biopharma has established a next-generation ADC technology platform called Hi-TOPi, on which the GPC3 ADC novel drug MRG006A is constructed. The key features of Hi-TOPi include: a linker that is highly stable in blood circulation and efficiently releases the toxin in tumor cells; a payload that is a novel TOP1 inhibitor with higher activity; as it is not a substrate of Pgp, it has the potential to overcome drug resistance; and it demonstrates excellent efficacy and safety in various preclinical tumor PDX and CDX models.
