Safety and Efficacy of Metabolically Armed GPC3 CAR-T Cells Injection (Meta10-GPC3) in Patients With Unresectable Recurrent/Metastatic Hepatocellular Carcinoma

A Study of Metabolically Armed GPC3 CAR-T Cells Injection (Meta10-GPC3) in Patients with Unresectable Recurrent/Metastatic Hepatocellular Carcinoma.

Study Overview

• Status: Not yet recruiting
• Conditions: Hepatocellular Carcinoma (HCC)
• Intervention / Treatment: Drug: Metabolically Armed GPC3 CAR-T cells

Detailed Description

This is an open-label study. This study is indicated for unresectable recurrent/metastatic hepatocellular carcinoma.The selections of dose levels and the number of subjects are based on clinical trials of similar products and the outcomes of our preliminary clinical studies.

1. Main research objectives:

   To evaluate the safety and tolerability of metabolically armed GPC3 CAR-T cells injection (Meta10-GPC3) in patients with unresectable recurrent/metastatic hepatocellular carcinoma.

2. Secondary research objectives:

(1)To evaluate the efficacy of metabolically armed GPC3 CAR-T-cell therapy in unresectable recurrent/metastatic hepatocellular carcinoma.

(2) To assess the in vivo pharmacokinetic (PK) profile, phenotype, and functional activity of infused GPC3 CAR-T cells.

• Study Type: Interventional
• Enrollment (Estimated): 27
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Qihan Fu; Phone Number: 18268173309; Email: ayfuqihan@126.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • The first affiliated hospital of medical college of zhejiang university
      • Contact: Qihan Fu; Phone Number: 18268173309; Email: ayfuqihan@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age >18 years and ≤75 years, male or female.
• Histologically confirmed recurrent or metastatic hepatocellular carcinoma (HCC) that is not amenable to surgical resection.
• At least one measurable target lesion according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
• Tumor tissue must test positive for GPC3 expression by immunohistochemical (IHC), defined as > 25% of tumor cells staining for GPC3 in the pathological specimen. Preferably, the target lesion sample should be used, including freshly obtained tumor tissue or archival tissue samples deemed acceptable by the investigator.
• Expected survival ≥ 12 weeks.
• Child-Pugh class A.
• Eastern Cooperative Oncology Group (ECOG) performance status was 0-1.
• For subjects who are HBsAg or HBcAb positive, HBV-DNA must be < 2 000 IU/mL; HBsAg-positive patients must receive antiviral therapy according to the Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2022 Edition).
• Adequate venous access for leukapheresis or venous blood collection.
• Hematologic parameters: WBC ≥ 2.5 × 10⁹/L, platelets ≥ 60 × 10⁹/L, Hb ≥ 9.0 g/dL, lymphocytes ≥ 0.4 × 10⁹/L.
• Biochemical parameters: Serum albumin ≥ 30 g/L; Lipase and amylase ≤ 1.5 × ULN; serum creatinine ≤ 1.5 × ULN and estimated creatinine clearance ≥ 40 mL/min; ALT and AST ≤ 5 × ULN; serum total bilirubin ≤ 2.5 × ULN; prothrombin time ≤ 4s longer above normal.
• Women or childbearing potential must have a negative serum pregnancy test within 14 days before CAR-T cell infusion and agree to use effective contraception for 12 months after infusion. Male subjects with partners of childbearing potential must having undergone a vasectomy or agree to use reliable contraception during the study period.
• Ability to understand and sign the informed consent form.

Exclusion Criteria:

• Pregnant or breastfeeding women, or women of childbearing potential who test positive on a pregnancy test during the screening period).
• Active hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection; seropositivity for Human Immunodeficiency (HIV) or syphilis.
• Any uncontrolled active infection, including but not limited to active pulmonary tuberculosis.
• Therapeutic doses of corticosteroids must be discontinued at least 2 weeks prior to Meta10-GPC3 infusion; any immunosuppressive medications must be discontinued at least 4 weeks before signing the informed consent form.
• History of hypersensitivity to immunotherapy or related agents, β-lactam antibiotics, or other severe allergic reactions.
• History or presence of hepatic encephalopathy.
• Clinically significant ascites, defined as ascites detectable on physical examination or requiring therapeutic intervention (excluding ascites detected only by imaging that does not require intervention).
• Imaging showing that HCC occupies ≥ 50 % of normal liver volume, or presence of tumor thrombus in the main portal vein or inferior vena cava.
• Clinically significant central-nervous-system (CNS) disorders (excluding subjects with CNS HCC metastases).
• Active or decompensated cardiac illness (requiring hospitalization or surgical intervention within the past 6 months), or poorly pression ≥ 160/100 mmHg uncontrolled with medication. Stable coronary artery disease or well-controlled hypertension is allowed.
• Active autoimmune disease requiring immunosuppressive therapy.
• Prior organ transplantation or currently on an organ transplant waiting list (including but not limited to liver transplantation).
• Any anti-HCC therapy within 2 weeks prior to leukapheresis or blood collection, including but not limited to surgical resection, interventional therapy, radiotherapy, chemotherapy, or immunotherapy.
• History or concurrent presence of other malignancies, except for the following: surgically removed non-melanoma skin cancer, cured cervical carcinoma in situ, localized prostate cancer, low-stage bladder cancer, ductal carcinoma in situ of the breast, or any malignancy without recurrence or treatment within the past 2 years.
• Other severe medical conditions, including but not limit to: poorly controlled diabetes (post-treatment HbA1c > 7 %), severe cardiac dysfunction (LVEF < 45 %), myocardial infarction, unstable angina, or unstable arrhythmia within 6 months, pulmonary embolism, chronic obstructive pulmonary disease, interstitial lung disease, forced expiratory volume in 1 second (FEV1) < 60 %, gastric ulcer, history of gastrointestinal bleeding, documented bleeding diathesis, uncontrolled thrombotic events, major bleeding, or DVT within 12 months prior to informed consent.
• Active neurological autoimmune or inflammatory disorders (e.g., Guillain-Barré syndrome, amyotrophic lateral sclerosis).
• History of QT-interval prolongation or severe cardiac disease.
• Any other condition deemed by the investigator to make the subject unsuitable for participation in the study (e.g., poor compliance).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Administration of Metabolically Armed GPC3 CAR-T Therapy; Patients undergo peripheral blood collection. Patients will receive a lymphodepletion chemotherapy with cyclophosphamide and fludarabine before CAR-T cells infusion. The study will design metabolically armed GPC3 CAR-T cells(Meta10-GPC3) with different structures. A dose of Meta10-GPC3 CAR-T cells will be infused on day 0.	Drug: Metabolically Armed GPC3 CAR-T cells; Each subject receive metabolically armed GPC3 CAR- T cells by intravenous infusion.; Other Names: Meta10-GPC3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (AEs)	To characterize the safety profile of Meta10-GPC3 in patients with unresectable recurrent/metastatic hepatocellular carcinoma as assessed by incidence of adverse events. Adverse events will be graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.	Within 2 years post Meta10-GPC3 infusion.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	To evaluate the proportion of participants who have a confirmed partial response (PR) and complete response (CR) per RECIST v1.1 as assessed by the investigator.	12 week, 20 week, 28 week, 40 week, 52 week, 78 week, 104 week post Meta10-GPC3 infusion.
Duration of Response (DOR)	To evaluate the duration from the time that criteria are met for CR or PR per RECIST v1.1 as assessed by the investigator until disease progression or death due to any cause.	12 week, 20 week, 28 week, 40 week, 52 week, 78 week, 104 week post Meta10-GPC3 infusion.
Progression-free survival (PFS)	The time from the start of Meta10-GPC3 treatment for the subjects to the first disease progression or death for any reason.	12 week, 20 week, 28 week, 40 week, 52 week, 78 week, 104 week post Meta10-GPC3 infusion.
Overall survival (OS)	OS is measured from the date of the infusion of Meta10-GPC3 to the date of the subjects' death.	12 week, 20 week, 28 week, 40 week, 52 week, 78 week, 104 week post Meta10-GPC3 infusion
The maximum concentration (Cmax)	The Cmax of CAR-T cell expansion in peripheral blood	Within 2 years post Meta10-GPC3 infusion.
Tmax	The time to reach the maximum concentration (Tmax)	Within 2 years post Meta10-GPC3 infusion.
AUC1-30d	The area under the curve AUC0-28d at 28 days.	Within 1 month post Meta10-GPC3 infusion.

Collaborators and Investigators

• Sponsor: Zhejiang University
• Collaborators: Leman Biotech Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): March 30, 2026
• Primary Completion (Estimated): December 15, 2028
• Study Completion (Estimated): April 15, 2029

Study Registration Dates

• First Submitted: March 17, 2026
• First Submitted That Met QC Criteria: March 17, 2026
• First Posted (Actual): March 23, 2026

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: April 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: IL-10; Meta10-GPC3; unresectable recurrent/metastatic hepatocellular carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: LM-META10-GPC3-13

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No