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Claudin18.2 CAR-T (CT041) in Patients With Gastric, Pancreatic Cancer, or Other Specified Digestive Cancers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04404595
Recruitment Status : Recruiting
First Posted : May 27, 2020
Last Update Posted : May 31, 2023
Sponsor:
Information provided by (Responsible Party):
CARsgen Therapeutics Co., Ltd.

Study Description
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Brief Summary:
A Phase 1b/2, open label, multi-center, clinical study of Chimeric Antigen Receptor T Cells (CAR-T) targeting claudin18.2 in patients with advanced gastric, pancreatic or other specified digestive system cancers

Condition or disease Intervention/treatment Phase
Gastric Cancer Pancreatic Cancer Biological: CT041 Phase 1 Phase 2

Detailed Description:

This is an open label, multi-center, Phase 1b/2 clinical trial to evaluate the safety and efficacy of autologous claudin18.2 chimeric antigen receptor T-cell therapy in patients with advanced gastric, pancreatic or other specified digestive system cancers.

Following consent, patients must have tumor tissue evaluated by CLDN18.2 IHC assay. Patients meeting all eligibility criteria will undergo a leukapheresis procedure to collect autologous mononuclear cells for manufacture of investigational drug product (CT041). Following manufacture of the drug product, subjects will receive preconditioning prior to CT041 infusion. All subjects will be asked to continue to undergo long-term gene safety follow-up.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: 3+3 dose escalation and expansion
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open-label, Multicenter, Phase 1b/2 Clinical Trial to Evaluate the Safety and Efficacy of Autologous Anti-claudin 18.2 Chimeric Antigen Receptor T-cell Therapy in Subjects With Advanced Gastric, Pancreatic, or Other Specified Digestive System Cancers
Actual Study Start Date : October 23, 2020
Estimated Primary Completion Date : June 1, 2025
Estimated Study Completion Date : September 1, 2035

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: anti-claudin18.2 chimeric antigen receptor T-cell therapy
Phase 1b will include two parts, dose escalation phase (Cohort A) followed by a dose expansion phase (Cohort B). Phase 2 (Cohort C) will evaluate the chosen dose in patients with advanced gastric cancer.
 Biological: CT041
treatment with anti-claudin18.2 chimeric antigen receptor T-cell infusion


Outcome Measures
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Primary Outcome Measures :
  1. Phase 1b: Incidence of Treatment Related adverse events (AEs) [ Time Frame: up to 18 mos ]
    Incidence of Treatment Related AEs, AEs of special interest and serious adverse events (SAEs)

  2. Phase 1b: Identification of Maximum Tolerated Dose (MTD) & incidence of Dose-limiting Toxicities (DLTs) [ Time Frame: day 1 - day 28 ]
    Incidence of dose-limiting toxicities (DLTs)

  3. Phase 2: Objective Response Rate (ORR) per independent central read [ Time Frame: up to 18 mos ]
    Rate of subjects experiencing >/= to PR per RECIST 1.1 as determined by IRC assessment


Secondary Outcome Measures :
  1. Phase 1b: Objective Response Rate (ORR) per local assessment [ Time Frame: up to 18 mos ]
    Rate of subjects experiencing >/= to PR per RECIST 1.1 as determined by investigator

  2. Phase 1b/2: Duration of Response [ Time Frame: up to 18 mos ]
    Duration of time from first response to progression of disease as determined by investigator

  3. Phase 1b/2: Disease Control Rate [ Time Frame: up to 18 mos ]
    Percentage of patients response at least 90 days as determined by investigator

  4. Phase 1b/2: Progression free survival [ Time Frame: up to 18 mos ]
    duration time after CT041 treatment that patient lives without worsening of disease as determined by investigator

  5. Phase 1b/2: Overall survival [ Time Frame: up to 18 mos ]
    duration time after CT041 treatment that patient lives as determined by investigator

  6. Phase 1b/2: Utilization of Hospital Resources [ Time Frame: up to 18 mos ]
    Days of hospitalization during & after CT041 infusion; days of hospitalization in ICU

  7. Phase 1b/2: Health-related Quality of Life (HRQoL) [ Time Frame: Baseline - month 18 ]
    Change from baseline in how subjects report the satisfaction with their health as reported on the EORTC QLQ-C30; scoring uses a linear transformation to standardize the raw score such that scores range from 0-100 with a higher score requesting a higher level or function or a higher level of symptoms.

  8. Phase 2: Incidence of Treatment Related adverse events (AEs) [ Time Frame: up to 18 mos ]
    Rate of subjects experiencing >/= to PR per RECIST 1.1 as determined by investigator

  9. Phase 1b/2: PK and bio-distribution of CT041 [ Time Frame: Baseline - month 18 ]
    Persistence of CAR transgene copy number

  10. Phase 1b/2: CLDN18.2 ICH Assay Performance [ Time Frame: Baseline - month 18 ]
    Correlation of CLDN18.2 expression level with tumor response

  11. Phase 1b/2: Anti-CT041 drug antibodies [ Time Frame: day 0 - month 18 ]
    Number of subjects with anit-CT041 drug antibodies

  12. Phase 1b/2: Cytokine expression level in blood after CT041 infusion [ Time Frame: day 0 - month 6 ]
    evaluate cytokine (IL-6 et al) expression levels in patients treated with CT041


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 76 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients are eligible for screening for potential inclusion in the study:

  1. Voluntarily signed the ICF;
  2. Age ≥ 18 and < 76 years with pathologically/histologically confirmed diagnosis of adenocarcinoma of the stomach or gastroesophageal junction, referred to collectively as STAD, or pancreatic adenocarcinoma (PAAD);
  3. Must have CLDN18.2-positive tumor expression as determined by the CLDN18.2 IHC assay;
  4. Failed or been intolerant of prior lines of systemic therapy;
  5. Estimated life expectancy > 4 months;
  6. At least 1 measurable lesion per RECIST 1.1;
  7. ECOG performance status of 0 or 1;
  8. Sufficient venous access for leukapheresis collection and no other contraindications to leukapheresis;
  9. Patients should have reasonable CBC counts, renal and hepatic functions;
  10. Women of childbearing age must undergo a serum pregnancy test with negative results before screening and infusion and be willing to use effective and reliable method of contraception;
  11. Men must be willing to use effective and reliable method of contraception for at least 12-months after T-cell infusion;
  12. Sufficient nutritional status.

Exclusion Criteria:

  1. Pregnant or lactating women;
  2. HIV, active hepatitis C virus (HCV), or active hepatitis B virus (HBV) infusion;
  3. Any uncontrolled active infection;
  4. AEs from previous treatment that have not recovered;
  5. Patients who have clinically significant thyroid dysfunction;
  6. Patients allergic to any drugs of the preconditioning regimen, tocilizumab, dimethyl sulfoxide (DMSO), or CT041 CAR-CLDN18.2 T-cell;
  7. Patients who have received prior cellular therapy such as (CAR T, TCR, tumor-infiltrating lymphocytes) or organ transplantation; Untreated central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression;
  8. Untreated CNS, leptomeningeal disease or cord compression
  9. Patients with heavy tumor burden such as significant lung disease
  10. Unstable/active ulcer or digestive tract bleeding or recent digestive surgery that may have increased risk of bleeding;
  11. Patients who have a history of esophageal or gastric resection with increased risk of bleeding or perforation;
  12. Patients requiring anticoagulant therapy such as warfarin or heparin;
  13. Patients requiring long-term antiplatelet therapy;
  14. Use of prednisone or other equivalent within 14 days before leukapheresis or preconditioning;
  15. Anticancer treatment within approximately 2 weeks prior to leukapheresis or approximately preconditioning;
  16. Major surgery less than 1 week prior to leukapheresis or 3 weeks prior to preconditioning;
  17. Patients have clinical significant cardiac conditions that researchers believe that participating in this clinical trial may endanger the health of the patients;
  18. Patients have clinical significant pulmonary conditions;
  19. Patients known to have active autoimmune diseases;
  20. Patients with second malignancies in addition to STAD or PAAD;
  21. Patients have significant neurologic disorders;
  22. Patients are unable or unwilling to comply with the requirements of clinical trial.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04404595


Contacts
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Contact: Hong Ma, MD Central Phone clinicalUS@carsgen.com

Locations
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United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Joseph Chao       lbatrow@coh.org   
University of Southern California Completed
Los Angeles, California, United States, 90089
UCSD Recruiting
San Diego, California, United States, 92093
Contact: G Botta       gbotta@health.ucsd.edu   
UCSF Recruiting
San Francisco, California, United States, 94143
Contact: Julia Carnevale         
United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: K Sprenger       kimberly.sprenger@moffitt.org   
United States, Kansas
University of Kansas Cancer Center Recruiting
Kansas City, Kansas, United States, 66160
Contact: Kasi Anup Kasi         
United States, Michigan
Karmanos Cancer Center Recruiting
Detroit, Michigan, United States, 48201
Contact: Mohammed Al Hallak         
United States, Minnesota
Mayo Cancer Hospital Recruiting
Rochester, Minnesota, United States, 55905
Contact: A Schimek       schimek.amanda@mayo.edu   
United States, New York
Northwell Cancer Institute Recruiting
New Hyde Park, New York, United States, 11042
Contact: Daniel King         
The Mount Sinai Hospital Recruiting
New York, New York, United States, 10029
Contact: Diedre Cohen         
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Geoffrey Ku         
United States, Ohio
Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: Anne Noonan         
United States, Texas
TX Oncology-Baylor Charles Sammons Cancer Center Recruiting
Dallas, Texas, United States, 75246
Contact: A. Rodriguez       Aimee.Rodriguez@BSWHealth.org   
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: M David       mfdavid@mdanderson.org   
United States, Wisconsin
Froedtert Hospital and the Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Cancer Center Clinical Trials Office    414-805-8900    CCCTO@mcw.edu   
Canada, Ontario
Princess Margaret Hospital Recruiting
Toronto, Ontario, Canada, M5GH 2C1
Contact: Eric Chen         
Sponsors and Collaborators
CARsgen Therapeutics Co., Ltd.
Investigators
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Principal Investigator: Harry H Yoon, MD Mayo
Principal Investigator: Dae Won Kim, MD Moffitt
More Information
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Responsible Party: CARsgen Therapeutics Co., Ltd.
ClinicalTrials.gov Identifier: NCT04404595    
Other Study ID Numbers: CT041-ST-02
First Posted: May 27, 2020    Key Record Dates
Last Update Posted: May 31, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by CARsgen Therapeutics Co., Ltd.:
CAR-T
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
 Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases