Clinical Trials /

Claudin18.2 CAR-T (CT041) in Patients With Gastric or Pancreatic Cancer

NCT04404595

Description:

A Phase 1b, open label, multi-center, clinical study of Chimeric Antigen Receptor T Cells (CAR-T) targeting claudin18.2 in patients with advanced gastric or pancreatic adenocarcinoma

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Adenocarcinoma
  • Pancreatic Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Claudin18.2 CAR-T (CT041) in Patients With Gastric or Pancreatic Cancer
  • Official Title: Open-label, Multicenter, Phase 1b Clinical Trial to Evaluate the Safety and Efficacy of Autologous Claudin 18.2 Chimeric Antigen Receptor T-cell Therapy in Patients With Advanced Gastric or Pancreatic Adenocarcinoma

Clinical Trial IDs

  • ORG STUDY ID: CT041-ST-02
  • NCT ID: NCT04404595

Conditions

  • Gastric Cancer
  • Pancreatic Cancer

Interventions

DrugSynonymsArms
CT041anti-claudin18.2 chimeric antigen receptor T-cell therapy

Purpose

A Phase 1b, open label, multi-center, clinical study of Chimeric Antigen Receptor T Cells (CAR-T) targeting claudin18.2 in patients with advanced gastric or pancreatic adenocarcinoma

Detailed Description

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

      Part A of the study will be Dose Escalation followed by Part B, an expansion cohort.
      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.
    

Trial Arms

NameTypeDescriptionInterventions
anti-claudin18.2 chimeric antigen receptor T-cell therapyExperimentalPhase 1 will include two parts, a dose escalation part to determine the recommended dose for the expansion part. During expansion patients will be treated with the recommended dose determined in the expansion part.
  • CT041

Eligibility Criteria

        Inclusion Criteria:

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

          1. Voluntarily signed the ICF;

          2. Age ≥ 18 and ≤ 80 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. Age ≥ 18 and ≤ 80 years with pathologically/histologically confirmed diagnosis of
             STAD, or PAAD who have failed or been intolerant of prior lines of systemic therapy;

          5. Estimated life expectancy > 12 weeks;

          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
             6 months after T-cell infusion;

        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. Patients with heavy tumor burden such as significant lung disease

          9. Unstable/active ulcer or digestive tract bleeding or recent digestive surgery that may
             have increased risk of bleeding;

         10. Patients who have a history of esophageal or gastric resection with increased risk of
             bleeding or perforation;

         11. Patients requiring anticoagulant therapy such as warfarin or heparin;

         12. Patients requiring long-term antiplatelet therapy;

         13. Use of prednisone or other equivalent within 14 days before leukapheresis or
             preconditioning;

         14. Anticancer treatment within approximately 2 weeks prior to leukapheresis or
             approximately 3 weeks before preconditioning;

         15. Major surgery less than 1 week prior to leukapheresis or 3 weeks prior to
             preconditioning;

         16. Patients have clinical significant cardiac conditions that researchers believe that
             participating in this clinical trial may endanger the health of the patients;

         17. Patients have clinical significant pulmonary conditions;

         18. Patients known to have active autoimmune diseases;

         19. Patients with second malignancies in addition to STAD or PAAD;

         20. Patients have significant neurologic disorders;

         21. Patients are unable or unwilling to comply with the requirements of clinical trial.
      
Maximum Eligible Age:80 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Treatment Related adverse events (AEs)
Time Frame:day 1 - month 12
Safety Issue:
Description:Incidence of Treatment Related AEs, AEs of special interest and serious adverse events (SAEs)

Secondary Outcome Measures

Measure:Evaluate the clinical efficacy of CT041 in patients with advanced gastric or pancreatic cancer after treatment with CT041
Time Frame:day 1 - month 12
Safety Issue:
Description:Time to progression by objective response evaluation criteria RECIST 1.1
Measure:Evaluate the clinical efficacy of CT041 in patients with advanced gastric or pancreatic
Time Frame:day 1 - month 12
Safety Issue:
Description:Duration of response by objective response evaluation criteria RECIST 1.1
Measure:Evaluate the clinical efficacy of CT041 in patients with advanced gastric or pancreatic
Time Frame:day 1 - month 12
Safety Issue:
Description:Disease control rate by objective response evaluation criteria RECIST 1.1
Measure:Evaluate the clinical efficacy of CT041 in patients with advanced gastric or pancreatic
Time Frame:day 1 - month 12
Safety Issue:
Description:Progression free survival by objective response evaluation criteria RECIST 1.1
Measure:Evaluate the clinical efficacy of CT041 in patients with advanced gastric or pancreatic
Time Frame:day 1 - month 12
Safety Issue:
Description:Overall survival

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Carsgen Therapeutics, Ltd.

Trial Keywords

  • CAR-T

Last Updated

May 26, 2020