Dual-target CAR-T therapy targeting mesothelin and CLDN18.2 for advanced pancreatic cancer

Dual-Target Chimeric Antigen Receptor (CAR) T-Cell Therapy Directed Against Mesothelin and Claudin 18.2 in Patients With Advanced or Metastatic Pancreatic Cancer

This treatment will try sequential CAR‑T cell infusions that target mesothelin and CLDN18.2 in people with unresectable or metastatic pancreatic adenocarcinoma who have received prior systemic therapy.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 21 Years to 90 Years
• Sex: All
• Sponsor: Essen Biotech (Academic / other)
• Drugs / interventions: CAR-T, chemotherapy, CAR T, immunotherapy
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT07066995 on ClinicalTrials.gov

What this trial studies

This phase 1/2 effort uses patients' own T cells that are engineered into two separate CAR‑T products—one targeting mesothelin and one targeting CLDN18.2—and gives them sequentially after lymphodepleting chemotherapy. Patients undergo leukapheresis for autologous cell manufacturing followed by a planned lymphodepletion regimen before the CAR‑T infusions. The trial enrolls adults with unresectable or metastatic pancreatic ductal adenocarcinoma who have progressed on prior systemic therapy and have ECOG 0–1 and adequate organ function. Safety, manufacturing feasibility, and anti‑tumor activity will be monitored, with attention to cytokine release syndrome and potential CLDN18.2‑related gastric toxicity.

Who should consider this trial

Good fit: Ideal candidates are adults with histologically confirmed unresectable or metastatic pancreatic ductal adenocarcinoma who have progressed after at least one systemic regimen, have ECOG performance status 0–1, expected survival ≥3 months, and meet required organ‑function criteria.

Not a fit: Patients whose tumors lack mesothelin or CLDN18.2 expression, who have poor performance status (ECOG ≥2) or significant organ dysfunction, or whose disease is resectable are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, the dual‑target approach could improve tumor control and produce deeper or more durable responses than single‑target therapies in advanced pancreatic cancer.

How similar studies have performed: Early‑phase studies of single‑antigen CAR‑T cells against mesothelin or CLDN18.2 have shown occasional remissions and disease control, but dual‑target CAR‑T in pancreatic cancer is a newer strategy with limited prior data.

Eligibility criteria

Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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;
* Situations considered unsuitable for inclusion by other researchers.

Where this trial is running

Beijing, Beijing Municipality

• District One Hospital — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Study coordinator: Rhoda M Smith, Phd

Conditions Pancreatic Cancer; Pancreatic Carcinoma; Pancreatic Cancer Non-resectable; Pancreatic Cancer Stage IV; claudin 18.2; CAR-T; Mesothelin