Clinical Trial of Autologous GPC3 CAR-T Cells (CBG166) Therapy for Advanced Hepatocellular Carcinoma

NCT06461624 | Recruiting Phase 1

• 1 other identifier: CRKBY-201
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

A phase I clinical study of 4th generation chimeric antigen receptor T Cells targeting glypican-3 ( CAR-GPC3 T Cells) in patients with advanced hepatocellular carcinoma.

Conditions

Advanced Hepatocellular Carcinoma

Keywords

GPC3; Chimeric antigen receptor T cell; Adoptive cell therapy

Outcome Measures

Primary Outcomes (3)

• Dose limiting toxicity (DLT)

  Describe the adverse events of limiting further increases in the dose of CBG166.

  Within 28 days of CAG166 infusion

• Adverse events

  Describe adverse events (AEs) and serious adverse events (SAEs) that are "likely" or "definitely" related to the study treatment that occur at any time of 24 months after treatment.

  Within 24 months after the treatment

• Maximum tolerated dose

  Determine the optimal agent for CBG166 CAR-T at maximum tolerated dose.

  From enrollment of the first subject to completion of follow-up of the last subject (up to 3 years)

Secondary Outcomes (12)

• Effectiveness evaluation

  At weeks 4, 8, and 18 and months 3, 4, 6, 9, 12, 15, 18 and 24 after cell infusion

• Effectiveness evaluation

  The efficacy is evaluated at weeks 4, 8, and 18 and months 3, 4, 6, 9, 12, 15, 18 and 24 after cell infusion

• Effectiveness evaluation

  The efficacy is evaluated at weeks 4, 8, and 18 and months 3, 4, 6, 9, 12, 15, 18 and 24 after cell infusion

• Effectiveness evaluation

  The efficacy is evaluated at weeks 4, 8, and 18 and months 3, 4, 6, 9, 12, 15, 18 and 24 after cell infusion

• Effectiveness evaluation

  The efficacy is evaluated at weeks 4, 8, and 18 and months 3, 4, 6, 9, 12, 15, 18 and 24 after cell infusion

Study Arms (1)

GPC3 CAR-T (CBG166)

EXPERIMENTAL

Biological: anti-GPC3 CAR-T

Interventions

anti-GPC3 CAR-T BIOLOGICAL

All subjects were intravenous administrated with CBG166.

Also known as: CBG166 CAR-T

GPC3 CAR-T (CBG166)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 to 70 years, male or female;
• Subjects voluntarily participated in the research and signed the Informed Consent Form (ICF) by themselves or their guardians;
• Unresectable stage B or C HCC according to the Barcelona Clinic Liver Cancer (BCLC) staging. In case of stage B, the subject must have disease progression following surgery or local treatment, or be unsuitable for surgery or local treatment;
• Subjects have previously received at least one systemic treatment regimen (including but not limited to targeted therapy, immunotherapy or chemotherapy) with disease progression determined by imaging during or after treatment;
• Cirrhosis status Child-Pugh score:≤7;
• Intrahepatic lesions were confirmed by imaging examination (arterial phase enhancement) within 28 days before the start of treatment. According to the RECIST1.1, there was at least one target lesion that could be stably evaluated;
• Expected survival time \> 12 weeks;
• Expression of GPC3 demonstrated by immunohistochemistry (IHC)
• ECOG Performance Status score: 0 to 1 point;
• Subjects should have adequate organ function;
• Subjects should be HBsAg negative. Subjects with positive HBsAg or positive HBcAb are required to have HBV-DNA \<2000 IU/ml;
• The blood pregnancy test of female subjects of childbearing age should be negative within 7 days before cell therapy and not during lactation; Female or male subjects of childbearing age need to take efficient tools or drug contraceptive measures during the whole research process or within one year after CAR-T cell transfusion (What happens later shall prevail);

You may not qualify if:

• Subjects with completely resectable liver tumors or who are eligible for liver transplantation;
• Pregnant or lactating women;
• Active bacterial or fungal infections within 72 hours prior to gonorrhea clearance (excluding subjects who have no evidence of active infections and antibiotics are not on the prohibited drug list, and continue to use prophylactic antibiotics, antifungal drugs, or antiviral drugs);
• Patients who had received systemic steroids equivalent to \> 15 mg/day prednisone within 2 weeks before apheresis, except those who had recently used or are currently using inhaled steroids;
• Before apheresis, Hb \< 80 g/L, ANC \< 1.0 × 109 /L or PLT \< 60 × 109 /L;
• Current clinically significant ascites, which is defined as ascites that are physically positive or require intervention (e.g., puncture or medication) for control (those whose imaging result shows ascites requiring no intervention may be included);
• Imaging results:≥50% of the liver is replaced by tumor or portal vein main tumor thrombus, or tumor thrombus invasion of mesenteric vein / inferior vena cava;
• Previous or present hepatic encephalopathy;
• Active brain metastasis;
• Subjects with a history of organ transplantation or waiting for organ transplantation (including liver transplantation);
• Any of the following situations exist: Hepatitis B core antibody (HBcAb) positive and hepatitis B virus (HBV) DNA in peripheral blood isperipheral blood hepatitis B virus (HBV) DNA ≥ 2000 IU/mL. Hepatitis C virus (HCV) antibody positive and HCV RNA positive. Human immunodeficiency virus (HIV) antibody positive. Syphilis test positive.
• Other serious medical conditions that may limit the patient's participation in this trial;
• Subjects who received anti-tumor therapy within 2 weeks prior to apheresis, or who received any investigational drug or systemic anti-tumor therapy within 28 days (or 5 half-lives of the drug, whichever is more appropriate in the judgment of the investigator) prior to signing the informed consent form;
• Prior treatment with any therapy that is targeted to GPC3;
• At the time of signing the informed consent, toxicity caused by previous PD-1/PD-L1 treatment had not returned to grade 1 or baseline levels, except for hair loss and pigmentation;

Sponsors & Collaborators

• Zhejiang University: lead
• Carbiogene Therapeutics Co. Ltd.: collaborator

Study Sites (2)

First Affiliated Hospital, Medical College of Zhejiang University

Hangzhou, Zhejiang, 310003, China

RECRUITING

the First Affiliated Hospital, School of Medicine, Zhejiang University

Hangzhou, Zhejiang, 310009, China

RECRUITING

Central Study Contacts

Qi Zhang, Associate professor

CONTACT

13819137113; qi.zhang@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 5, 2024
• First Posted: June 17, 2024
• Study Start: July 1, 2024
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): October 31, 2027
• Last Updated: November 6, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)