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A Safety and Efficacy Study of Allogeneic CAR Gamma-Delta T Cells in Subjects with Relapsed/Refractory Solid Tumors (CAR001)

E

Ever Supreme Bio Technology

Status and phase

Enrolling
Phase 2
Phase 1

Conditions

Solid Tumor

Treatments

Biological: HLA-G-CAR.BiTE allogeneic γδ T cells

Study type

Interventional

Funder types

Industry

Identifiers

NCT06150885
ES-CCAR01-A3301

Details and patient eligibility

About

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).

Full 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)

Enrollment

60 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  1. Male or female subjects aged ≥ 18 years

  2. 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.

  3. With at least one measurable lesion as defined by RECIST1.1 (for TNBC, NSCLC or CRC) or RANO (for GBM)

  4. Able to understand and sign the ICF

  5. Have a life expectancy of > 12 weeks

  6. ECOG performance status ≤ 1

  7. Recovered from any previous therapy related toxicity to ≤ grade 2 at screening

  8. With adequate renal function: serum creatinine ≤ 1.5 X ULN; eGFR > 50 ml/min

  9. 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

  10. With PT and PTT ≤ 1.5X ULN

  11. 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

  1. Has received any allogeneic cell therapy before screening

  2. With known or suspected to be hypersensitivity to CAR001 or its excipients, such as DMSO or human serum albumin

  3. With more than one kind of active diagnosed primary cancer

  4. With active infection requiring systemic medication

  5. 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

  6. Has been diagnosed as HIV positive (confirmed by anti-HIV and nucleic acid test)

  7. 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

  8. With historical or current auto-immune diseases, such as rheumatoid arthritis, type I diabetes, psoriasis or systemic lupus erythematosus

  9. Has uncontrolled psychiatric disorder by medical history

  10. Has CNS diseases except GBM or stroke

  11. Has received any investigational therapy from another clinical study within 4 weeks

  12. Inability to undergo radiological assessment, such as MRI or CT for any reason

  13. Has received radiotherapy or chemotherapy within 2 weeks (but palliative radiation therapy (R/T) for pain control are allowed)

  14. Not suitable to participate the trial as judged by the investigator

  15. 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.
  16. 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)

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

60 participants in 1 patient group

CAR001
Experimental group
Description:
CAR001 cells mixed with normal saline will be administered to patients.
Treatment:
Biological: HLA-G-CAR.BiTE allogeneic γδ T cells

Trial contacts and locations

1

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Central trial contact

Sammi Hsu; Vincent Lee

Data sourced from clinicaltrials.gov

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