Clinical trial · Interventional
Dual-Target CAR-NK Cells Targeting Mesothelin (MSLN) and MUC1 in Advanced Pancreatic Ductal Adenocarcinoma
A Phase 1/2, Open-label, Biomarker-guided, Dose-escalation and Expansion Study of Dual-targeting CAR-NK Cells Directed Against Mesothelin (MSLN) and MUC1, With an Exploratory CLDN18.2/MUC1 Dual-target Cohort, in Patients With Unresectable or Metastatic Pancreatic Ductal Adenocarcinoma (PDAC)
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (3)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Metastatic Disease | Pancreatic Neoplasm | PROBABILISTIC | 0.70 |
| Pancreatic Ductal Adenocarcinoma (PDAC) | Pancreatic Ductal Adenocarcinoma | ONTOLOGY_EXACT | 0.85 |
| Unresectable Locally Advanced | — | UNRESOLVED | — |
Interventions
Interventions (3)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| EB-DNK101 dual-targeting CAR-NK cells (MSLN + MUC1) | Biological | — | UNRESOLVED |
| EB-DNK102 dual-targeting CAR-NK cells (CLDN18.2 + MUC1) | Biological | — | UNRESOLVED |
| Lymphodepleting chemotherapy (Flu/Cy) | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Arm A: EB-DNK101 (MSLN/MUC1 Dual-CAR NK)
- description
- Participants with PDAC whose tumors express MSLN and/or MUC1 per central IHC are assigned to Arm A.
- interventionNames
- Biological: EB-DNK101 dual-targeting CAR-NK cells (MSLN + MUC1)
- Biological: EB-DNK102 dual-targeting CAR-NK cells (CLDN18.2 + MUC1)
- Drug: Lymphodepleting chemotherapy (Flu/Cy)
- type
- EXPERIMENTAL
- label
- Arm B: EB-DNK102 (CLDN18.2/MUC1 Dual-CAR NK)
- description
- Participants with PDAC whose tumors express CLDN18.2 and/or MUC1 per central IHC are assigned to Arm B.
- interventionNames
- Biological: EB-DNK101 dual-targeting CAR-NK cells (MSLN + MUC1)
- Biological: EB-DNK102 dual-targeting CAR-NK cells (CLDN18.2 + MUC1)
- Drug: Lymphodepleting chemotherapy (Flu/Cy)
Primary outcomes (3)
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
- Maximum age
- 75 Years
Show eligibility criteria text
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.
References
Publications (0)
Data not yet available