A Safety and Efficacy Study of Allogeneic CAR Gamma-Delta T Cells in Subjects with Relapsed/Refractory Solid Tumors

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:

• ANC ≥ 1,000 cells/μl
• Platelets ≥ 75,000 counts/μl
• Total WBC ≥ 2,000 cells/μl
• Hemoglobin ≥ 8 g/dL

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:

• Is lactating; or
• Has a positive pregnancy test result at eligibility checking; or
• Refuses to adopt at least two form of birth control from signing informed consent to 1 year after the last administration of CAR001.
• 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:

• Established use of oral, injected, or implanted hormonal methods of contraception that have comparable efficacy (failure rate < 1 %), for example hormone vaginal ring or transdermal hormone contraception
• Placement of an intrauterine device or intrauterine system
• Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps)