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

NCT ID: NCT06150885

Last Updated: 2024-12-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-09-01

Study Completion Date

2027-09-30

Brief Summary

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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

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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)

Conditions

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Solid Tumor

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Single Group Assignment
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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CAR001

CAR001 cells mixed with normal saline will be administered to patients.

Group Type EXPERIMENTAL

HLA-G-CAR.BiTE allogeneic γδ T cells

Intervention Type BIOLOGICAL

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.

Interventions

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HLA-G-CAR.BiTE allogeneic γδ T cells

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.

Intervention Type BIOLOGICAL

Eligibility Criteria

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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.


* 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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ever Supreme Bio Technology Co., Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Wen-Liang Huang, MD

Role: STUDY_CHAIR

Ever Supreme Bio Technology Co., Ltd.

Locations

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China Medical University Hospital

Taichung, Non-US, Taiwan

Site Status RECRUITING

Countries

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Taiwan

Central Contacts

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Sammi Hsu

Role: CONTACT

+886422052121

Vincent Lee

Role: CONTACT

+886422052121

Facility Contacts

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Der-Yang Cho, MD

Role: primary

Tao-Wei Ke, MD

Role: backup

References

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Huang SW, Pan CM, Lin YC, Chen MC, Chen Y, Jan CI, Wu CC, Lin FY, Wang ST, Lin CY, Lin PY, Huang WH, Chiang YT, Tsai WC, Chiu YH, Lin TH, Chiu SC, Cho DY. BiTE-Secreting CAR-gammadeltaT as a Dual Targeting Strategy for the Treatment of Solid Tumors. Adv Sci (Weinh). 2023 Jun;10(17):e2206856. doi: 10.1002/advs.202206856. Epub 2023 Apr 20.

Reference Type BACKGROUND
PMID: 37078788 (View on PubMed)

Other Identifiers

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ES-CCAR01-A3301

Identifier Type: -

Identifier Source: org_study_id