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

CARsgen Therapeutics

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Gastric Cancer; Pancreatic Cancer

Treatments: Biological: CT041

Study type: Interventional

Funder types: Industry

Identifiers

NCT04404595

CT041-ST-02

Details and patient eligibility

About

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

Full 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.

Enrollment: 110 estimated patients

Sex: All

Ages: 18 to 76 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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110 participants in 1 patient group

anti-claudin18.2 chimeric antigen receptor T-cell therapy

Experimental group

Description:

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.

Treatment:

Biological: CT041