Hepatocellular Carcinoma
Conditions
Brief summary
This study is designed to determine the safety and efficacy of CAR-GPC3 T cells in patients with relapsed or refractory hepatocellular carcinoma. Single or multiple doses of GPC3-targeted CAR T cells will be given to subjects with unmet medical needs for which there are no effective therapies known at this time.
Detailed description
A single arm, open-label pilot study is designed to determine the safety, tolerability and engraftment potential of CAR-GPC3 T cells in patients with GPC3-positive hepatocellular carcinoma. Primary objectives: Determine the safety, tolerability and cytokinetics of the autologous T cells transduced with the anti- GPC3 lentiviral vector in patients with hepatocellular carcinoma. Secondary objectives: Make a preliminary evaluation on the efficacy of CAR-GPC3 T cells in patients with hepatocellular carcinoma by the following parameters: Objective response rate (ORR); Disease Control Rate (DCR); Time of tumor progression (TTP); Overall survival (OS).
Interventions
GENETICCAR-GPC3 T cells
Self-controlled dose escalation will be applied to the first 3 - 6 subjects enrolled. Classical 3+3 dose escalation will be applied to subsequent subjects based on the self-controlled dose escalation study.
Sponsors
CARsgen Therapeutics Co., Ltd.
RenJi Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Age of 18-70 years; 2. Pathologically confirmed advanced hepatocellular carcinoma (HCC); 3. ≥1 measurable target lesion per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1); 4. Tumor tissue positive for GPC3 expression per immunohistochemical staining (IHC) assay; 5. Estimated survival \> 12 weeks; 6. Child-Pugh grade A; 7. ECOG performance score of 0-1; 8. HBV-DNA \< 200 IU/mL if positive for HBsAg or HBcAb. Patients positive for HBsAg shall receive anti-viral treatment per The guideline of prevention and treatment for chronic hepatitis B: a 2015 update; 9. Have adequate venous access for apheresis or venous blood collection; 10. White blood cells ≥ 2.5 x 109/L, platelet ≥ 60×109/L, haemoglobin ≥ 9.0 g/dL, lymphocyte ≥ 0.4×109/L 11. Serum albumin ≥ 30 g/dL, serum lipase and amylase≤1.5 upper limit of normal (ULN), serum creatinine ≤ 1.5 ULN and endogenous creatinine clearance ≥ 40mL/min, ALT and AST ≤ 5 ULN, Serum total bilirubin ≤ 2.5 ULN, Prothrombin Time is less than 4s longer than normal; 12. Negative serum pregnancy test within 14 days before CAR T infusion, and with willingness to use reliable contraceptive methods to avoid pregnancy until 12 months after CAR T infusions for females of childbearing age; Having undergone sterilization procedure or with willingness to use reliable contraceptive methods to avoid pregnancy for males with female partner of childbearing age during the study; 13. Able to understand and sign the informed consent form
Exclusion criteria
If the patient meets any of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerance | 24 weeks | Study related adverse events are defined as signs above CTCAE Grade 3, laboratory toxicities and clinical events occurred at any time from the first day of infusion to week 24 that are possibly, likely, or definitely related to the study, including infusion related toxicity and CAR-GPC3 T cells related toxicity. Include but not limited to: Fever; Chills; Nausea, vomiting and other gastrointestinal symptoms; Fatigue; Hypotension; Respiratory distress; Tumor lysis syndrome; Cytokine release syndrome; Neutropenia, thrombocytopenia; Liver and kidney dysfunction; Other toxicities. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Engraftment | 2 years | Duration of in vivo survival of CAR-GPC3 T cells is defined as engraftment. The primary engraftment endpoint is the number of DNA vector copies per mL blood of CAR-GPC3 T cells at regular intervals through week 4 following the initial infusion. Q-PCR for CAR-GPC3 vector sequences will be performed until any 2 sequential tests are negative, documented as engraftment and persistence of CAR-GPC3 T cells. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Anti-tumor responses to CAR-GPC3 T cell infusions | 2 years | Objective response rate (ORR); Progression-free survival (PFS); Time of tumor progression (TTP); Overall survival (OS). |
Countries
China
Outcome results
None listed