Preliminary Clinical Study of Autologous T Cells Modified Chimeric Antigen Receptor (CAR) Targeting GPC3 for the Treatment of Recurrent or Refractory Lung Squamous Cell Carcinoma
Overview
- Phase
- Phase 1
- Intervention
- CAR-GPC3 T Cells
- Conditions
- Lung Squamous Cell Carcinoma
- Sponsor
- CARsgen Therapeutics Co., Ltd.
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Safety and tolerance: Occurrence of study related adverse events
- Last Updated
- 9 years ago
Overview
Brief Summary
The purpose of this study is to observe and confirm the safety, tolerance and cell pharmacokinetics of lentivirus-transduced CAR-GPC3 T cells (CAR-GPC3 T cells targeting GPC3)
Detailed Description
A single-center, open-label pilot study to determine the safety, tolerance and engraftment potential of CAR-GPC3 T cells in subjects with GPC3+ positive lung squamous cell carcinoma. Primary objectives: Observe and determine the safety and tolerance in escalating dose infusion of CAR-GPC3 T cells (CAR T cells targeting GPC3) transduced with the lentiviral vector, and the survival of the CAT-GPC3 T cells in vivo, referred to as engraftment potential. Secondary objectives: The following indexes are monitored for curative effect of CAR-GPC3 T cells on lung squamous cell carcinoma: 1. Objective response rate (ORR), is defined as the ratio of patients diagnosed as partial remission (PR) to complete remission (CR) according to RECIST 1.1 criteria. 2. Progression free survival (PFS), is defined as the duration from baseline to PD (audited and confirmed by independent imaging), or to the day of any death event. The earlier one shall prevail. 3. Time to tumor progression (TTP), is defined as the duration from baseline to disease starts to get worse or spreads to other parts of the body. 4. Overall survival (OS), is defined as the time period from the 1st day of treatment to the day of death for any reason. For patients who are still alive at the data analysis day, OS data is subject to the last confirmed time of survival patients.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Men or women aged 18\~70 years old
- •Subjects are diagnosed as refractory, recurrent ,metastatic, advanced lung squamous cell carcinoma by histological and cytological methods including specific lesion-targeted brush biopsy, lavage and fine needle aspiration;
- •Have at least one new measurable tumor lesion compared with previous irradiated region
- •Tumor tissues samples confirmed as GPC3-positive
- •Expected survival≥12 weeks
- •ECOG scored as 0-1 or KPS grading \> 80
- •ANC≥1500/nm3
- •PLT≥100000/mm3
- •Serum creatinine≤2.5mg/dL，CCR≥50ml/min (renal malfunction defined as CCR\<50ml/min according to Cockroft-Gault formula)
- •ALT and AST≤2.5ULN; for liver metastasis，ALT and AST ≤5ULN
Exclusion Criteria
- •CAR-T positive rate \< 10%
- •pregnant women or women in lactation
- •active HBV or HCV infection
- •HIV/AIDS infection
- •active infection
- •previously suffered from diseases or concurrent diseases as followed：
- •patients confirmed as severe autoimmune diseases in long-term (over 2 months) need of systemic immune inhibitors (steroid) or as immune-mediated symptomatic diseases including ulcerative colitis, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus (SLE), autoimmune vasculitis (for example, Wegener's granulomatosis)
- •subjects with previous diagnosis as motor neurone disease caused by autoimmunity
- •subjects previously suffered from toxic epidermal necrolysis (TEN)
- •subjects with any mental diseases including dementia, mental status change that may impinge the understanding and performance of informed consent and related questionnaire
Arms & Interventions
CAR-GPC3 T cells
Intravenous infusion with escalating dose is adopted in this study. Total dosage: 1 x 10\^5 - 2 x 10\^9 CAR-GPC3 T cells/kg The next dose and interval depends on the response of the subject to previous dose. Lymphodepletion: Fludarabine: 30 mg/m\^2/day x 4 days; Cyclophosphamide: 500 mg/m\^2/day x 2 days. Adjustment is in discretion of the investigator based on individual response.
Intervention: CAR-GPC3 T Cells
CAR-GPC3 T cells
Intravenous infusion with escalating dose is adopted in this study. Total dosage: 1 x 10\^5 - 2 x 10\^9 CAR-GPC3 T cells/kg The next dose and interval depends on the response of the subject to previous dose. Lymphodepletion: Fludarabine: 30 mg/m\^2/day x 4 days; Cyclophosphamide: 500 mg/m\^2/day x 2 days. Adjustment is in discretion of the investigator based on individual response.
Intervention: Fludarabine
CAR-GPC3 T cells
Intravenous infusion with escalating dose is adopted in this study. Total dosage: 1 x 10\^5 - 2 x 10\^9 CAR-GPC3 T cells/kg The next dose and interval depends on the response of the subject to previous dose. Lymphodepletion: Fludarabine: 30 mg/m\^2/day x 4 days; Cyclophosphamide: 500 mg/m\^2/day x 2 days. Adjustment is in discretion of the investigator based on individual response.
Intervention: Cyclophosphamide
Outcomes
Primary Outcomes
Safety and tolerance: Occurrence of study related adverse events
Time Frame: 24 weeks
Occurrence of study related adverse events, defined as laboratory toxicities and clinical events that are possibly, likely or definitely related to study treatment at any time from the infusion until week 24. This will include infusive toxicity, and any toxicity possibly related to the CAR-GPC3 T cells.
Secondary Outcomes
- Engraftment: the DNA vector copies per mL blood of CAR-GPC3 T cells(2 years)