4th Generation Chimeric Antigen Receptor T Cells Targeting Glypican-3

NCT03980288 | Completed Phase 1 DMC

• 1 other identifier: CISLD-4
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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

Advanced hepatocellular Carcinoma; CAR-T; GPC3

Outcome Measures

Primary Outcomes (1)

• Dose limited toxicity and Maximum Tolerated Dose

  Safety and tolerability

  After 28 days of single infusion

Secondary Outcomes (8)

• Number of cells

  Through week 52 or the second timepoint of cells undetectable

• Number of participants with treatment-related adverse events

  Through study completion, an average of 3 years

• Antitumor efficacy-Progression-free survival (PFS)

  Through study completion, an average of 3 years

• Antitumor efficacy-Duration of response (DOR)

  Through study completion, an average of 3 years

• Antitumor efficacy-Duration of disease control (DDC)

  Through study completion, an average of 3 years

Study Arms (1)

CAR-GPC3 T Cells

EXPERIMENTAL

The subjects enrolled will be sequentially assigned to Part 1 at 3 dose levels via typical 3+3 dose escalation method and then Part 2, cohort expansion stage, 3 cohorts of CAR T therapy combination with currently available treatment for HCC. stage Part 1: Dose escalating: 3 dose level Part 2: 3 cohorts Cohort 1. Combination with tyrosine kinase inhibitors Cohort 2. Combination with PD-1 / PD-L1 monoclonal antibody Cohort 3. Combination with the drugs may benefit for patient at investigator's discretion

Drug: CAR-GPC3 T Cells

Interventions

CAR-GPC3 T Cells DRUG

Pretreatment with fludarabine and cyclophosphamide CAR-GPC3 T Cells infusion

CAR-GPC3 T Cells

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 to 75 years, male or female;
• Patients with advanced hepatocellular carcinoma (HCC) diagnosed by histopathology or cytology who are not suitable for surgery or local treatment, have developed progressive disease or intolerability after standard systemic therapies (including but not limited to systemic chemotherapy, molecular targeted therapy);
• According to BCLC, the patients are classified into Grade C or Grade B unsuitable for local treatment/progressive disease after local treatment;
• In tumor tissue samples GPC3 is detected positive by immunohistochemistry (IHC);
• According to RECIST 1.1, patients have at least one evaluable target lesion, defined as: the longest diameter of non-lymph node lesion ≥ 10 mm, or the shortest diameter of lymph node lesion ≥ 15 mm); hepatic lesions require arterial phase contrast enhancement;
• Expected survival is \> 12 weeks;
• Cirrhosis status Child-Pugh score:≤7;
• ECOG Performance Status score: 0 to 1 point;
• If the patient is HBsAg positive or HBcAb positive, HBV-DNA should be \<200 IU/ml. HBsAg positive patients must receive antiviral treatment according to the 2015 China Edition of Guideline for Chronic Hepatitis B Prevention and Treatment;
• Subjects should have adequate organ functions before screening and pre-treatment (at baseline);
• Have venous accesses for pheresis;
• Subjects of childbearing age must undergo a serum pregnancy test within 14 days before the initiation of the study and the result must be negative. In addition, they should be willing to use a reliable method of contraception during the trial (within 52 weeks after cell infusion); male subjects whose spouses are women of childbearing age should undergo sterilization surgery or agree to use a reliable method of contraception during the trial;
• Understand and sign informed consent.

You may not qualify if:

• Pregnant or breast-feeding women;
• HCV-RNA, HIV antibodies or Syphilis Serological tests are positive;
• Any uncontrollable active infection, including but not limited to active tuberculosis;
• Subjects have clinically significant thyroid dysfunction determined by investigator (serum thyroid hormone assays TT4, TT3, FT3, FT4, and serum thyroid stimulating hormone TSH) which is not suitable for entering into the study;
• Previous or present hepatic encephalopathy;
• 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;
• Patients with known active autoimmune diseases which require to be treated with immunosuppressive agents including biological agents;
• The side effects caused by the previous treatment of the subjects did not return to CTCAE ≤1; except hair loss and other tolerable events determined by investigator;
• Patients who had received systemic steroids or other immunosuppressive agents within 2 weeks before collection of mononuclear cells, except those who had recently used or are currently using inhaled steroids;
• Allergic to immunotherapy and related drugs;
• Subjects have untreated or symptomatic brain metastases;
• Subjects have central or extensively metastases in lung;
• Subjects with unstable or active ulcers and gastrointestinal bleeding currently;
• Patients with a history of organ transplantation or waiting for organ transplantation (including liver transplantation);

Sponsors & Collaborators

• Zhejiang University: lead
• CARsgen Therapeutics Co., Ltd.: collaborator

Study Sites (1)

First affiliated hospital, Zhejiang University

Hangzhou, Zhejiang, 310006, China

Location

Study Officials

• Tingbo Liang

  The First Affiliated Hospital, Zhejiang University

  PRINCIPAL INVESTIGATOR

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 2, 2019
• First Posted: June 10, 2019
• Study Start: July 23, 2019
• Primary Completion: December 30, 2020
• Study Completion: December 30, 2020
• Last Updated: January 31, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)