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

NCT06150885 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: ES-CCAR01-A3301
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) of CAR001 for Phase I part

  MTD was determined by testing increasing doses once a week for 4 weeks via IV on dose escalation cohorts 1 to 5 with 3 to 6 participants each. MTD reflects the highest dose of drug that did not cause a Dose-Limiting Toxicity (DLT) in \> 33% of participants. DLTs were defined as any AE ≥ grade 3 (CTCAE v5.0) that is considered to be causally related (possibly, probably, or definitely related) to CAR001 within 4 weeks.

  4 weeks after last dosing of CAR001

• Objective Response Rate (ORR) of CAR001 for Phase IIa part

  The rate of subjects with CR or PR based on RECIST1.1 in patients with NSCLC, TNBC or CRC; RANO in patients with GBM. Although there is no control group in this study, the ORR after CAR001 administration could be compared to baseline.

  from visit 1 to 24-months of safety and efficacy follow-up period

Secondary Outcomes (9)

• Safety - AEs and SAEs incidences over the study period

  from visit 1 to 24-months of safety and efficacy follow-up period

• Safety - Vital signs assessments at each post-treatment

  from visit 1 to 24-months of safety and efficacy follow-up period

• Safety - Laboratory examinations at each post-treatment

  from visit 1 to 24-months of safety and efficacy follow-up period

• Safety - 12-lead electrocardiogram (ECG) assessments at each post-treatment

  from visit 1 to 24-months of safety and efficacy follow-up period

• Safety - Physical Examination at each post-treatment

  from visit 1 to 24-months of safety and efficacy follow-up period

Study Arms (1)

CAR001

EXPERIMENTAL

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

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

Interventions

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

CAR001

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• Ever Supreme Bio Technology Co., Ltd.: lead

Study Sites (1)

China Medical University Hospital

Taichung, Non-US, 404, Taiwan

RECRUITING

Related Publications (1)

• 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.

  PMID: 37078788 BACKGROUND

Study Officials

• Wen-Liang Huang, MD

  Ever Supreme Bio Technology Co., Ltd.

  STUDY CHAIR

Central Study Contacts

Sammi Hsu

CONTACT

+886422052121; cthsu@ever-supreme.com.tw

Vincent Lee

CONTACT

+886422052121; rd004@ever-supreme.com.tw

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single Group Assignment

Study Record Dates

• First Submitted: November 13, 2023
• First Posted: November 29, 2023
• Study Start: September 1, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: December 3, 2024

Record last verified: 2024-09

Locations

TW (1)