A Single Arm, Open Label, Dose-escalation Phase I and Dose-expansion Phase IIa Clinical Study to Evaluate the Feasibility, Safety, and Efficacy of Allogeneic Chimeric Antigen Receptor (CAR) Gamma-Delta T Cells CAR001 in Subjects with Relapsed/refractory Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- HLA-G-CAR.BiTE allogeneic γδ T cells
- Conditions
- Solid Tumor
- Sponsor
- Ever Supreme Bio Technology Co., Ltd.
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Objective Response Rate (ORR) of CAR001 for Phase IIa part
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
This study is composed of phase I and IIa parts. The dose-escalation phase I part aims to find the maximum tolerated dose (MTD) and to identify the safety of CAR001 in subjects with relapsed/refractory solid tumor; the dose-expansion phase IIa part aims to evaluate the potential efficacy of CAR001 in subjects with relapsed/refractory non-small cell lung cancer (NSCLC), triple negative breast cancer (TNBC), colorectal cancer (CRC) or Glioblastoma multiforme (GBM).
Detailed Description
Primary Objective: Phase I: To evaluate the safety of CAR001 in subjects. Phase IIa: To provide potential evidence for the clinical efficacy of CAR001 in improving tumor response rate in subjects. Secondary Objectives: To evaluate the safety and potential efficacy of CAR001 in subjects. Exploratory: Level of CAR-positive γδT cells in peripheral blood from baseline to subsequent visits. (Time Frame: 12 months after the last infusion)
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female subjects aged ≥ 18 years
- •For phase I part, subjects with histologically confirmed diagnosis of solid tumor with expression of PD-L1 ≥ 1% and are relapsed/refractory to at least two lines of standard-of-care therapy. For phase IIa part, subjects with histologically confirmed diagnosis of TNBC, NSCLC, CRC or GBM with expression of PD-L1 ≥ 1%, and are relapsed/refractory to at least two lines of standard-of-care therapy.
- •With at least one measurable lesion as defined by RECIST1.1 (for TNBC, NSCLC or CRC) or RANO (for GBM)
- •Able to understand and sign the ICF
- •Have a life expectancy of \> 12 weeks
- •ECOG performance status ≤ 1
- •Recovered from any previous therapy related toxicity to ≤ grade 2 at screening
- •With adequate renal function: serum creatinine ≤ 1.5 X ULN; eGFR \> 50 ml/min
- •With adequate liver function: ALT, AST, and ALP ≤ 3X ULN or ≤ 5 X ULN if liver metastases; and total bilirubin ≤ 1.5X ULN or ≤ 3 X ULN if due to Gilbert's disease
- •With PT and PTT ≤ 1.5X ULN
Exclusion Criteria
- •Has received any allogeneic cell therapy before screening
- •With known or suspected to be hypersensitivity to CAR001 or its excipients, such as DMSO or human serum albumin
- •With more than one kind of active diagnosed primary cancer
- •With active infection requiring systemic medication
- •With medical conditions who are receiving systemic steroid therapy \>10 mg prednisone/day or equivalent dose, or other immune-suppressants in the past 2 weeks
- •Has been diagnosed as HIV positive (confirmed by anti-HIV and nucleic acid test)
- •With acute cardiovascular disease; NYHA classification ≥ 3; or history of myocardial infarction during the past 6 months; or has active uncontrolled arterial hypertension by medical history. Per investigator's judgment, would not make participation appropriate
- •With historical or current auto-immune diseases, such as rheumatoid arthritis, type I diabetes, psoriasis or systemic lupus erythematosus
- •Has uncontrolled psychiatric disorder by medical history
- •Has CNS diseases except GBM or stroke
Arms & Interventions
CAR001
CAR001 cells mixed with normal saline will be administered to patients.
Intervention: HLA-G-CAR.BiTE allogeneic γδ T cells
Outcomes
Primary Outcomes
Objective Response Rate (ORR) of CAR001 for Phase IIa part
Time Frame: from visit 1 to 24-months of safety and efficacy follow-up period
The rate of subjects with CR or PR based on RECIST1.1 in patients with NSCLC, TNBC or CRC; RANO in patients with GBM. Although there is no control group in this study, the ORR after CAR001 administration could be compared to baseline.
Maximum Tolerated Dose (MTD) of CAR001 for Phase I part
Time Frame: 4 weeks after last dosing of CAR001
MTD was determined by testing increasing doses once a week for 4 weeks via IV on dose escalation cohorts 1 to 5 with 3 to 6 participants each. MTD reflects the highest dose of drug that did not cause a Dose-Limiting Toxicity (DLT) in \> 33% of participants. DLTs were defined as any AE ≥ grade 3 (CTCAE v5.0) that is considered to be causally related (possibly, probably, or definitely related) to CAR001 within 4 weeks.
Secondary Outcomes
- Safety - AEs and SAEs incidences over the study period(from visit 1 to 24-months of safety and efficacy follow-up period)
- Safety - Vital signs assessments at each post-treatment(from visit 1 to 24-months of safety and efficacy follow-up period)
- Safety - Physical Examination at each post-treatment(from visit 1 to 24-months of safety and efficacy follow-up period)
- Efficacy - Change of ECOG Performance Status Scale(from visit 1 to 24-months of safety and efficacy follow-up period)
- Safety - Laboratory examinations at each post-treatment(from visit 1 to 24-months of safety and efficacy follow-up period)
- Safety - 12-lead electrocardiogram (ECG) assessments at each post-treatment(from visit 1 to 24-months of safety and efficacy follow-up period)
- Efficacy - Progression Free Survival (PFS) rate(from visit 1 to 24-months of safety and efficacy follow-up period)
- Efficacy - Overall Survival (OS) rate(from visit 1 to 24-months of safety and efficacy follow-up period)
- Efficacy - Change of QoL from baseline(from visit 1 to 24-months of safety and efficacy follow-up period)