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
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
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).
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)
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
With adequate hematopoietic function:
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
Has received any investigational therapy from another clinical study within 4 weeks
Inability to undergo radiological assessment, such as MRI or CT for any reason
Has received radiotherapy or chemotherapy within 2 weeks (but palliative radiation therapy (R/T) for pain control are allowed)
Not suitable to participate the trial as judged by the investigator
Female subject of childbearing potential who:
Male subject with a female spouse/partner who is of childbearing potential refuses to adopt at least two forms of birth control from signing informed consent to 1 year after the last administration of CAR001.
For exclusion criteria #15 and #16, acceptable forms of birth control include:
cthsu@ever-supreme.com.tw+886422052121
rd004@ever-supreme.com.tw+886422052121