A Safety and Efficacy Study of Allogeneic CAR Gamma-Delta T Cells 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
Ever Supreme Bio Technology Co., Ltd.
60 participants
Sep 1, 2024
INTERVENTIONAL
Conditions
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).
Eligibility
Inclusion Criteria15
- 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 Criteria22
- 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.
- 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)
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Interventions
Phase I is a multiple escalating dose, single arm, open-label and 3+3 design that implemented with five cohorts: low dose for single administration, low dose for twice administrations for 2 weeks, low, middle and high dose for 4 repeated administrations for 4 weeks. Phase IIa is a single-arm, open-label and dose-expansion study and the effective dose of CAR-positive cells will be administered to 27 evaluable subjects with TNBC, NSCLC, CRC or GBM via intravenous infusion weekly for 4 weeks.
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT06150885