Mesothelin and Claudin 18.2 Dual-Target CAR-T Therapy in Advanced Pancreatic Cancer

NCT07066995 | Recruiting Phase 1 DMC

• 1 other identifier: ESBI202571-102
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Autologous T-cells engineered to express CARs targeting Mesothelin and Claudin18.2, for Unresectable locally advanced or metastatic pancreatic adenocarcinoma (Pancreatic Ductal Adenocarcinoma, PDAC), administered as two separate sequential infusions following lymphodepleting chemotherapy

Conditions

Pancreatic Cancer; Pancreatic Carcinoma; Pancreatic Cancer Non-resectable; Pancreatic Cancer Stage IV

Keywords

Pancreatic Cancer; claudin 18.2; Pancreatic Carcinoma; CAR-T; Mesothelin

Outcome Measures

Primary Outcomes (1)

• Incidence and severity of dose-limiting toxicities (DLTs) following chemotherapy preparative regimen and infusion of CD19/BCMA chimeric antigen receptor (CAR) T cells

  Will be recorded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 at three dose levels until the maximum tolerated dose (MTD) is determined.

  28 days

Secondary Outcomes (1)

• Rate of successful manufacture and expansion of the Mesothelin and Claudin 18.2 chimeric antigen receptor (CAR) T cells

  60 days

Study Arms (1)

Mesothelin and Claudin 18.2 CAR T cells, chemotherapy

EXPERIMENTAL

Patients will be administered fludarabine phosphate intravenously (IV) over a 30-minute period on days -4 to -2. Additionally, cyclophosphamide will be administered intravenously (IV) over 60 minutes on day -2. Subsequently, patients will receive Mesothelin and Claudin 18.2 CAR T cells intravenously (IV) over a duration of 10-20 minutes on day 0. Patients who exhibit positive responses to the initial dose of Mesothelin and Claudin 18.2 CAR T cells, do not experience unacceptable side effects, and have a sufficient quantity of cells available may be eligible to receive 2 or 3 additional doses of Mesothelin and Claudin 18.2 CAR T cells.

Biological: Mesothelin and Claudin 18.2 CAR-T cells

Interventions

Mesothelin and Claudin 18.2 CAR-T cells BIOLOGICAL

The intervention in this clinical trial involves a novel approach using Mesothelin and Claudin 18.2 Chimeric Antigen Receptor T (CAR T) cells combined with chemotherapy. The goal is to assess safety and efficacy in patients with specific hematologic malignancies. Treatment Regimen: Fludarabine Phosphate (Days -4 to -2): IV administration of fludarabine phosphate over 30 minutes on days -4 to -2. It's part of the preparatory regimen to enhance the body's response to CAR T-cell therapy. Cyclophosphamide (Day -2): IV cyclophosphamide over 60 minutes on day -2. Mesothelin and Claudin 18.2 Chimeric Antigen Receptor T Cells (Day 0): IV administration of investigational therapy, Mesothelin and Claudin 18.2 CAR T cells, over 10-20 minutes on day 0. Additional Doses: Eligible patients responding well to the initial Mesothelin and Claudin 18.2 CAR-T cell infusion without unacceptable side effects and sufficient CAR-T cell availability may receive 2 or 3 additional doses.

Mesothelin and Claudin 18.2 CAR T cells, chemotherapy

Eligibility Criteria

• Age: 21 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Expected survival time ≥3 months;
• Histologically or cytologically confirmed pancreatic adenocarcinoma that is advanced (unresectable or metastatic). Patients should have received, or be intolerant of, standard first-line therapy (e.g., gemcitabine/nab-paclitaxel, FOLFIRINOX) for advanced disease. A short course of current first-line therapy is allowed for the purpose of bridging to manufacturing, but evidence of disease progression on or after at least one line is required prior to infusion (for the dose-expansion phase, patients must have progressed on ≥1 prior systemic regimen).
• ECOG Performance Status: 0 or 1 (fully active or restricted in strenuous activity but ambulatory).
• Liver and kidney function, cardiopulmonary function meet the following requirements:
• Creatinine ≤1.5×ULN; (2) Electrocardiogram showed no clinically significant abnormal bands;
• Blood oxygen saturation \>91% in non-oxygen state;
• Total bilirubin ≤2×ULN; ALT and AST≤2.5 x ULN; ALT and AST abnormalities due to disease, such as liver infiltration or bile duct obstruction, were determined to be less than 5×ULN. If Gilbert syndrome is diagnosed, the total bilirubin index can be relaxed to ≤3.0×ULN and the direct bilirubin ≤1.5×ULN.
• No serious mental disorders;
• Can understand this test and has signed the informed consent.

You may not qualify if:

• Hepatitis B surface antigen (HBsAg) positive; Hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer detection is not within the normal reference value range; Hepatitis C virus (HCV) Antibody positive and peripheral blood hepatitis C virus (HCV) RNA positive; Human immunodeficiency virus (HIV) Antibody positive; Syphilis positive;
• Serious heart disease, including but not limited to unstable angina, myocardial infarction or bypass or stent surgery (within 6 months prior to screening), congestive heart failure (NYHA classification ≥III), and severe arrhythmia;
• Systemic diseases that are deemed unstable by researchers: including but not limited to severe liver, kidney, or metabolic diseases that require drug treatment;
• Active or uncontrollable infections (except mild genitourinary and upper respiratory tract infections) that require systemic treatment within 7 days prior to administration;
• Pregnant or lactating women, and female subjects who plan pregnancy within 2 years after cell transfusion or male subjects whose partners plan pregnancy within 2 years after cell transfusion;
• Patients who received CAR-T therapy or other gene-modified cell therapy before screening;
• Participated in other clinical studies 1 month before screening;
• Evidence of central nervous system invasion during subject screening;
• Mental patients with depression or suicidal thoughts;

Sponsors & Collaborators

• Essen Biotech: lead

Study Sites (1)

District One Hospital

Beijing, Beijing Municipality, 086-373, China

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Mesothelin

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

GPI-Linked Proteins; Membrane Glycoproteins; Glycoproteins; Glycoconjugates; Carbohydrates; Intracellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Lipid-Linked Proteins; Membrane Proteins; Antigens, Surface; Antigens; Biological Factors

Central Study Contacts

Rhoda M Smith, Phd

CONTACT

+12077706670; clinical-trials@essen-biotech.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Open-label clinical trials are a category of clinical research where the masking is minimal or nonexistent. In such trials, both the participants and the researchers are fully aware of the treatment assignments, which means participants know the treatment they are receiving, and researchers are aware of each participant's treatment group.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a Phase 1/2, first-in-human, open-label, non-randomized trial of sequential dual-target CAR-T cell therapy in subjects with advanced pancreatic cancer

Study Record Dates

• First Submitted: July 4, 2025
• First Posted: July 15, 2025
• Study Start: April 29, 2025
• Primary Completion (Estimated): December 10, 2027
• Study Completion (Estimated): December 28, 2028
• Last Updated: July 15, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)