Lepu Biopharma: The world’s first GPC3 ADC to publish clinical results achieves clinical breakthrough in liver cancer
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.
