Status:

ACTIVE_NOT_RECRUITING

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

Lead Sponsor:

CARsgen Therapeutics Co., Ltd.

Conditions:

Gastric Cancer

Pancreatic Cancer

Eligibility:

All Genders

18-76 years

Phase:

PHASE1

PHASE2

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 sys...

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,...

Eligibility Criteria

Inclusion

  • Inclusion Criteria:
  • Patients are eligible for screening for potential inclusion in the study (\* indicates inclusion criteria at Baseline (for subjects to be eligible for preconditioning)):
  • Voluntarily signed the ICF;
  • 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);or biliary tract cancers (BTCs, including intrahepatic/extrahepatic cholangiocarcinoma and gallbladder cancer but not ampullary carcinoma);
  • Must have CLDN18.2-positive tumor expression as determined by the CLDN18.2 IHC assay;
  • Estimated life expectancy \> 4 months\*;
  • Failed or been intolerant of prior lines of systemic therapy:
  • For screening:
  • Leukapheresis can be performed for subjects with STAD who have progressed or were intolerant of at least 1 prior line of systemic therapy, or,
  • Leukapheresis can be performed for subjects with PAAD who are receiving first-line treatment, or,
  • Leukapheresis can be performed for subjects with BTC who are receiving first-line treatment.
  • Baseline\*:
  • Subjects with STAD who have progressed or were intolerant of at least 2 prior lines of systemic therapy, or,
  • Subjects with PAAD who have progressed or were intolerant of at least 1 prior line of systemic therapy, or,
  • Subjects with BTC who have progressed or were intolerant of at least 1 prior line of systemic therapy. For subjects with CCA with who has FGFR2 fusions or rearrangements, or IDH1-mutant must have received FDA-approved target therapies.
  • At least 1 measurable lesion per RECIST 1.1\*;
  • ECOG performance status of 0 or 1\*;
  • Sufficient venous access for leukapheresis collection and no other contraindications to leukapheresis;
  • Patients should have adequate CBC counts, renal and hepatic functions\*;
  • 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\*;
  • Men must be willing to use effective and reliable method of contraception for at least 12-months after T-cell infusion\*;
  • Sufficient nutritional status.
  • Exclusion Criteria for screening (\* indicates exclusion criteria for baseline as well):
  • Pregnant or lactating women\*;
  • HIV, active hepatitis C virus (HCV), active hepatitis B virus (HBV), or active syphilis infection;
  • Any active infection requiring systemic treatment\*;
  • AEs from previous treatment that have not recovered\*;
  • Patients who have clinically significant thyroid dysfunction;
  • Patients allergic to any drugs of the preconditioning regimen, tocilizumab, dimethyl sulfoxide (DMSO), or CT041 CAR-CLDN18.2 T-cell;
  • Patients who have received:
  • prior cellular therapy such as (CAR T, TCR, tumor-infiltrating lymphocytes) within one year.
  • organ transplantation.
  • previous anti-claudin18.2 CAR T-cell therapy, mRNA-based cancer immunotherapy, or bispecific T cell engager.
  • Untreated central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression;
  • Patients with heavy tumor burdens;
  • Unstable/active ulcer, anastomotic recurrence with full-thickness tumor infiltration or tumor involving any major vessels, digestive tract bleeding, or recent digestive surgery that may have increased risk of bleeding\*;
  • Patients who have a history of esophageal or gastric resection plus current evidence of locally recurrent tumor that involves any major blood vessels or that has evidence of recent bleeding or perforation\*;
  • Patients requiring anticoagulant therapy such as warfarin or heparin;
  • Patients requiring long-term antiplatelet therapy;
  • Use of prednisone \>/= 10mg daily or other equivalent steroids within 14 days before leukapheresis or preconditioning\*;
  • Anticancer treatment within approximately 2 weeks prior to leukapheresis or preconditioning\*;
  • Major surgery less than 1 week prior to leukapheresis or 3 weeks prior to preconditioning\*;
  • Patients who have clinically significant cardiac conditions that researchers believe that participating in this clinical trial may endanger the health of the patients\*;
  • Inadequate pulmonary function\*;
  • Patients known to have active autoimmune diseases;
  • Patients with second malignancies;
  • Patients have significant neurologic disorders;
  • Patients are unable or unwilling to comply with the requirements of clinical trial.
  • Additional exclusion criteria solely for baseline (prior to conditioning regimen):
  • Fever \> 38.0°C;
  • Active illness or existing toxicity that would place the subject at undue risk;
  • Abrupt deterioration of clinical status or condition;
  • Subjects who have received a live attenuated vaccine 4 weeks before preconditioning.
  • Inclusion Criteria Before Infusion: There are no inclusion criteria at this timepoint.
  • Exclusion Criteria Before Infusion:
  • Patients who have clinically significant cardiac conditions that researchers believe that participating in this clinical trial may endanger the health of the patients;
  • Inadequate pulmonary function;
  • Active infection requiring systemic therapy or causing fever within 7 days prior to investigational infusion;
  • Active illness or toxicity that would place the subject at undue risk;
  • Abrupt deterioration of clinical status or condition;
  • New or worsening Grade ≥ 3 non-hematologic toxicities.

Exclusion

    Key Trial Info

    Start Date :

    October 23 2020

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ESTIMATED

    End Date :

    September 1 2035

    Estimated Enrollment :

    110 Patients enrolled

    Trial Details

    Trial ID

    NCT04404595

    Start Date

    October 23 2020

    End Date

    September 1 2035

    Last Update

    January 8 2025

    Active Locations (16)

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    Page 1 of 4 (16 locations)

    1

    City of Hope

    Duarte, California, United States, 91010

    2

    University of Southern California

    Los Angeles, California, United States, 90089

    3

    UCSD

    San Diego, California, United States, 92093

    4

    UCSF

    San Francisco, California, United States, 94143

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