Dual-Target CAR-NK Cells Targeting Mesothelin (MSLN) and MUC1 in Advanced Pancreatic Ductal Adenocarcinoma

Summary

This example study evaluates the safety, tolerability, and preliminary anti-tumor activity of investigational, dual-targeting chimeric antigen receptor natural killer (CAR-NK) cell products for patients with advanced pancreatic ductal adenocarcinoma (PDAC). Participants are assigned to one of two biomarker-defined cohorts based on tumor antigen expression: (A) Mesothelin (MSLN) and/or MUC1, or (B) Claudin 18.2 (CLDN18.2) and/or MUC1. The study uses a dose-escalation followed by dose-expansion design to define a recommended Phase 2 dose (RP2D) and to estimate response rates in each cohort.

Eligibility

Inclusion Criteria:

* Age 18 to 75 years at the time of consent.
* Histologically or cytologically confirmed pancreatic ductal adenocarcinoma (PDAC).
* Unresectable locally advanced or metastatic disease with progression after at least 1 prior standard systemic therapy regimen, or intolerance/ineligibility for standard therapy.
* At least 1 measurable lesion per RECIST v1.1.
* Tumor antigen expression by central IHC (archival or fresh biopsy): • Arm A eligibility: MSLN positive and/or MUC1 positive. • Arm B eligibility: CLDN18.2 positive and/or MUC1 positive. (Example threshold: IHC 2+ or 3+ staining in \>=50% of tumor cells, or H-score above protocol-defined cutoff.)
* ECOG performance status 0-1.
* Adequate organ function (example): ANC \>= 1.0 x 10\^9/L; platelets \>= 75 x 10\^9/L; hemoglobin \>= 8 g/dL; AST/ALT \<= 3x ULN (\<= 5x ULN with liver metastases); total bilirubin \<= 1.5x ULN; creatinine clearance \>= 50 mL/min.
* Life expectancy \>= 12 weeks.
* Negative pregnancy test for individuals of childbearing potential; agreement to use effective contraception during study participation and for a protocol-defined follow-up period.
* Ability to understand and willingness to sign written informed consent.

Exclusion Criteria:

* Active or untreated CNS metastases or carcinomatous meningitis.
* Clinically significant uncontrolled infection (including uncontrolled bacterial, fungal, or viral infection).
* Known active hepatitis B or hepatitis C with detectable viral load; known uncontrolled HIV infection.
* Prior allogeneic hematopoietic stem cell transplant or solid organ transplant.
* Prior gene-modified cellular therapy (e.g., CAR-T/CAR-NK) within 6 months or prior therapy targeting the same antigen(s) Ongoing requirement for systemic immunosuppressive therapy (e.g., chronic corticosteroids above physiologic replacement).
* Clinically significant cardiovascular disease (e.g., recent myocardial infarction, uncontrolled arrhythmia, or NYHA class III/IV heart failure) within a protocol-defined period.
* Active autoimmune disease requiring systemic treatment in the past 2 years (replacement therapy allowed).
* Pregnant or breastfeeding.
* Any medical, psychiatric, or social condition that, in the investigator's opinion, would interfere with safe participation or interpretation of results.

Conditions4

Interventions3

Related trials

• Dual-Targeting CAR-NK Cells Targeting Mesothelin (MSLN) and MUC1 in Advanced Pancreatic Ductal Adenocarcinoma — Beijing Biotech

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