Chimeric Antigen Receptor T Cells Targeting Glypican-3

NCT03884751 | Completed Phase 1 DMC

• 1 other identifier: CT011-HCC-01
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 6

Brief Summary

A Phase I Clinical Study of Chimeric Antigen Receptor T Cells Targeting Glypican-3 (CAR-GPC3 T Cells) in Patients with Advanced Hepatocellular Carcinoma

Conditions

Hepatocellular Carcinoma

Keywords

Hepatocellular Carcinoma; CAR-T

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicity (DLT)

  Safety

  After 28 days of single infusion

• Maximum tolerated dose (MTD)

  tolerability

  After 28 days of single infusion

Secondary Outcomes (9)

• Pharmacokinetics (the copies of cells in vivo)

  Day0~Week 26

• Pharmacokinetics ( the duration of survival of cells in vivo)

  Day0~Week 26

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  Month 24

• Antitumor efficacy-Progression-free survival (PFS)

  Month 24

• Antitumor efficacy-Duration of response (DOR)

  Month 24

Study Arms (1)

CAR-GPC3 T Cells

EXPERIMENTAL

The subjects are enrolled into 2 dose levels cohorts in sequence

Biological: CAR-GPC3 T Cells

Interventions

CAR-GPC3 T Cells BIOLOGICAL

CAR-GPC3 T Cells injection

Also known as: Chimeric Antigen Receptor T Cells Targeting Glypican-3

CAR-GPC3 T Cells

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;
• Patients with advanced hepatocellular carcinoma (HCC) diagnosed by histopathology or cytology who are not suitable for surgery or local treatment (including ablation, intervention, and radiotherapy), have developed progressive disease or intolerability after standard systemic therapies (including but not limited to systemic chemotherapy, molecular targeted therapy) and have no effective treatment at the time of enrollment;
• 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;
• In tumor tissue samples GPC3 is detected positive by immunohistochemistry (IHC);
• According to Barcelona Clinic Liver Cancer staging(BCLC), the patients are classified into Grade C or Grade B unsuitable for local treatment/progressive disease after local treatment;
• Expected survival is \> 12 weeks;
• Cirrhosis status Child-Pugh score: Grade A;
• Eastern Cooperative Oncology Group(ECOG) Performance Status score: 0 to 1 point;
• Without active hepatitis B and/or Hepatitis C;
• Have venous accesses for pheresis;
• Acceptable routine blood test showing no contraindication to the lymphodepletion pretreatment;
• Adequate liver, renal, cardiovascular, respiratory function;
• 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 24 months (M24) 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(Hepatitis C Virus RNA ), HIV antibodies or Syphilis Serological tests are positive;
• HBV（Hepatitis B） and HCV(Hepatitis C virus ) infection exist simultaneously;
• Any uncontrollable active infection
• Patients who had received systemic steroids or other immunosuppressive agents
• Previous or present hepatic encephalopathy;
• Current clinically significant ascites;
• ≥50% of the liver is replaced by tumor or portal vein main tumor thrombus, or tumor thrombus invasion of mesenteric vein / inferior vena cava;
• Metastases to the central nervous system and clinically significant central nervous system diseases;
• Patients with existing heart disease in need of treatment or hypertension that be poorly controlled
• Patients with known active autoimmune diseases which require to be treated with immunosuppressive agents including biological agents;
• Patients with a history of organ transplantation or waiting for organ transplantation (including liver transplantation);
• Patients with local treatments such as surgical treatment, interventional therapy, radiotherapy, ablation or systemic chemotherapy were performed for the studied disease within 2 weeks prior to apheresis;Or received immunotherapy (PD-1/ PD-L1 monoclonal antibody, see Section 15) or any Chinese herbal or proprietary medicine for the control of liver cancer within 1 week prior to apheresis;Or received sorafenib, regofenib, ramvastinib and other tyrosine kinase inhibitor targeted drugs within 1 week prior to apheresis;Targeted therapy with anti-angiogenic monoclonal antibodies such as bevacizumab or its analogue 4 weeks prior to apheresis;
• Patiens with previous treatment with targeted GPC3, TCR-T or CAR-T;
• Patients who previously received anti-PD-1/ PD-L1 monoclonal antibody therapy within 4 weeks prior to apheresis;

Sponsors & Collaborators

• CARsgen Therapeutics Co., Ltd.: lead
• NanJing PLA 81 Hospital: collaborator
• First Affiliated Hospital of Zhejiang University: collaborator
• RenJi Hospital: collaborator

Study Sites (6)

Nanfang Hospital of Southern Medical University

Guangzhou, Guangdong, 510000, China

Location

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450000, China

Location

The 81st Hospital of Chinese PLA

Nanjing, Jiangsu, 210002, China

Location

Renji Hospital Shang Hai Jiaotong Unversity of Medicine

Shanghai, Shanghai Municipality, 200001, China

Location

Zhongshan Hospital of Fudan University

Shanghai, Shanghai Municipality, 200001, China

Location

The First Affiliated Hospital Zhejiang University

Hangzhou, Zhejiang, 310006, China

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Qin shukui, Pro

  The 81st Hospital of PLA

  PRINCIPAL INVESTIGATOR

• Zhai bo, Pro

  RenJi Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2019
• First Posted: March 21, 2019
• Study Start: August 15, 2019
• Primary Completion: May 28, 2021
• Study Completion: December 3, 2021
• Last Updated: February 24, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (6)