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: 2

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 unresectable local advanced or metastatic solid tumor with expression of both PD-L1 and HLA-G positive are relapsed/refractory to at least two lines of standard-of-care therapy, or unwilling to undergo standard therapies.
• Relapse is defined as disease progression after last regimen; refractory is defined as intolerable or progressing disease (PD), or stable disease (SD) to the last regimen.
• For phase IIa part, subjects with histologically confirmed diagnosis of unresectable local advanced or metastatic BC, NSCLC, CRC or GBM with expression of both PD-L1 and HLA-G positive, and are relapsed/refractory to at least two lines of standard-of-care therapy, or unwilling to undergo standard therapies.
• Relapse is defined as disease progression after last regimen; refractory is defined as intolerable or progressing disease (PD) to the last regimen or stable disease (SD) without meaningful clinical benefit as determined by the investigator.
• The standard-of-care therapies of phase IIa for each disease are listed:
• BC: Subject failed to anthracycline-containing (such as Doxorubicin and Epirubicin), taxane-containing (such as Paclitaxel and Docetaxel), antimetabolites (such as Capecitabine, Gemcitabine and Fluorouracil) or platinum-based (such as Cisplatin and Carboplatin) chemotherapy, microtubule dynamic inhibitor (such as Eribulin and Vinorelbine) and/or targeted therapy such as antibody drug conjugate (such as Sacituzumab govitecan-hzi), PARP inhibitor, germline BRCA1/BRCA2 mutation (such as Olaparib and Talazoparib), HER2-targeted therapy for HER2-positive disease and endocrine therapy for hormone receptor-positive disease..
• NSCLC: Subject failed to targeted therapies (according to the genetic testing results), such as Gefitinib and Afatinib and/or platinum-containing, pemetrexed, docetaxel chemotherapy with or without Immune checkpoint inhibitors (such as PD-1 or PD-L1 inhibitor: Atezolizumab, Nivolumab, and Pembrolizumab). For subject with non-squamous cell carcinoma using Immune checkpoint inhibitor, subjects should be with EGFR/ALK/ROS-1 wild type; for subject with squamous cell carcinoma using Immune checkpoint inhibitor, subjects should be with EGFR/ALK wild type.
• CRC: Subject failed to chemotherapies (i.e. Folinicacid/ 5-fluorouracil/oxaliplatin (FOLFOX) and Folinicacid/ 5-fluorouracil/irinotecan (FOLFIRI)) and/or target therapies, including anti-EGFR (K-RAS and N-RAS wild type) (such as Cetuximab and Panitumumab) or anti-VEGF (such as Bevacizumab), Regorafenib and Lonsurf, according to the genetic testing results) GBM: Subject failed to chemotherapy (such as Temozolomide (TMZ)) Carmustine implant (such as Gliadel Wafer) and/or anti-VEGF (such as Bevacizumab) treatment
• With at least one measurable lesion as defined by RECIST1.1 (for BC, NSCLC or CRC) or RANO (for GBM). For subjects with GBM, the maximum longest diameter (or perpendicular diameter for CNS lesions) not exceeding 3.0 cm (≤ 3.0 cm) at screening.
• Able to understand and sign the informed consent form (ICF)
• Have a life expectancy of \> 12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
• Recovered from any previous therapy related toxicity to ≤ grade 2 at screening
• With adequate renal function: serum creatinine ≤ 1.5X upper limit of normal (ULN); estimated glomerular filtration rate (eGFR) \> 50 ml/min

You may not qualify if:

• Has received autologous cell therapy or autologous tissue transplantation within 180 days before CAR001 infusion; or with a history of allogeneic or xenogeneic transplant, gene therapy or BiTE therapy
• 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
• With active infection of hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), or human T-lymphotropic virus (HTLV) at the time of Screening. Suspected SARS-CoV-2 confirmed positive by PCR, or suspected tuberculosis infection.
• Active HBV infection (chronic or acute), defined as having a positive hepatitis B surface antigen (HBsAg) test during Screening. Subjects with a past or resolved HBV infection, defined as having a negative HBsAg test and a positive total hepatitis B core antibody (HBc Ab) test at screening are eligible for the study if HBV deoxyribonucleic acid (DNA) test is ≤ 1000 copies/mL.
• Active HCV infection, defined as having a positive HCV antibody test followed by a positive HCV ribonucleic acid (RNA) test during Screening. The HCV RNA test will be performed only for subjects who have a positive HCV test. Subjects with a history of treated HCV can be enrolled if negative by HCV PCR with investigator approval.
• With acute cardiovascular disease; New York Heart Association (NYHA) classification ≥ 3; or history of myocardial infarction during the past 6 months; or has active uncontrolled arterial hypertension by medical history; Or cardiac LVEF ≤ 40%, evidence of pericardial effusion as determined by echocardiogram (ECHO), and clinically significant pleural effusion; or uncontrolled cardiac arrhythmia; or cardiac enzyme levels including N-terminal -pro B type natriuretic peptide (NT-proBNP) \> 450 pg/ml (age \<50 yrs); \> 900 pg/ml (age 50-75 yrs); \> 1,800 pg/ml (age \>75 yrs) by blood sampling. 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 central nerve system (CNS) diseases except GBM or stroke (acute stroke within 6 months is excluded)
• With treated CNS metastases (by whole brain radiation therapy, surgery or radiosurgery, etc.) are permitted on study if all of the following are met:
• CNS metastases have been clinically stable for at least 4 weeks and baseline scans show no evidence of new or worsening CNS metastases
• With medical conditions who are on a stable dose of ≤10mg/day of prednisone or equivalent for at least 2 weeks

Sponsors & Collaborators

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

Study Sites (2)

China Medical University Hospital

Taichung, Non-US, 404, Taiwan

RECRUITING

National Taiwan University Hospital

Taipei, 100, 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: September 9, 2026

Record last verified: 2026-09

Locations

TW (2)