Open-Label, Multicenter, Phase 1b /2 Clinical Trial to Evaluate the Safety and Efficacy of Autologous Anti-claudin18.2 Chimeric Antigen Receptor T-cell Therapy in Subjects with Advanced Gastric, Pancreatic, or Other Specified Digestive System Cancers
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.
Cohort A Primary -Evaluate the safety and tolerability of CAR-CLDN18.2 T-cell therapy (CT041) in patients with advanced STAD or PAAD -Identify the MTD and a RP2D of CT041 therapy in patients with STAD or PAAD Secondary: -Evaluate clinical efficacy outcomes with CAR-CLDN18.2 T-cell therapy (CT041) in patients with advanced STAD or PAAD Exploratory: -Evaluate PK and biodistribution of CAR-CLDN18.2 T-cell therapy (CT041) in patients with STAD or PAAD -Evaluate the performance of CLDN18.2 IHC assay in patients with STAD or PAAD -Evaluate anti-CAR-CLDN18.2 T-cell therapy (CT041) drug antibodies in patients with STAD or PAAD Cohort B Primary: -Determine the efficacy of CAR-CLDN18.2 T-cell therapy (CT041), in terms of ORR in patients with PAAD Secondary -Evaluate the safety and tolerability of CAR-CLDN18.2 T-cell therapy (CT041) in patients with PAAD -Evaluate additional clinical efficacy outcomes with CAR-CLDN18.2 T-cell therapy (CT041) in patients with PAAD Exploratory -Evaluate PK and biodistribution of CAR-CLDN18.2 T-cell therapy (CT041) in patients with PAAD -Evaluate the performance of CLDN18.2 IHC assay in patients with PAAD -Evaluate anti-CAR-CLDN18.2 T-cell therapy (CT041) drug antibodies in patients with PAAD
CT041 (); Nab-paclitaxel (Abraxane); cyclophosphamide (); cytoxan (cyclophosphamide); fludarabine (Fludarabine phosphate)
- Voluntarily signed the ICF
- Age >18 and > Cohort A and B: Patients with STAD, PAAD or BTC
- Cohort C: Patients with STAD
- Must have CLDN18.2-positive tumor expression from a tumor sample collected > Life expectancy > 4 months
- Must have prior lines of therapy defined by protocol
- 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 reasonable 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 for at least 12 months after T-cell infusion.
- Men must be willing to use effective and reliable method of contraception for at least 12 months after T-cell infusion
- Sufficient nutritional status: Must must weigh >/= 38kg and females must weight >/= 34 kg. Patients must have > Additional criteria will apply
- Pregnant or lactating women
- HIV, active hepatitis C virus (HCV), active hepatitis B virus (HBV) or active syphilis infection. History of treated hepatitis B or C is permitted if the viral load is undetectable per qPCR and/or nucleic acid testing.
- Any uncontrolled active infection
- 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) or organ transplantation; Untreated central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression
- Patients with heavy tumor burden such as significant lung disease
- Unstable/active ulcer or digestive tract bleeding or recent digestive surgery that may have increased risk of bleeding
- Patients who have a history of esophageal or gastric resection with increased risk of bleeding or perforation
- Patients requiring anticoagulant therapy such as warfarin or heparin
- Patients requiring long-term antiplatelet therapy
- Use of prednisone or other equivalent within 14 days before leukapheresis or preconditioning
- Anticancer treatment within approximately 2 weeks prior to leukapheresis or approximately 3 weeks before preconditioning
- Major surgery less than 1 week prior to leukapheresis or 3 weeks prior to preconditioning
- Patients have clinical significant cardiac conditions that researchers believe that participating in this clinical trial may endanger the health of the patients
- Patients have clinical significant pulmonary conditions
- Patients known to have active autoimmune diseases
- Patients with second malignancies in addition to STAD or PAAD
- Patients have significant neurologic disorders
- Patients are unable or unwilling to comply with the requirements of clinical trial.
- Additional criteria will apply
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