Dual-Targeting CAR-NK Cells Targeting Mesothelin (MSLN) and MUC1 in Advanced Pancreatic Ductal Adenocarcinoma
DUAL-NK-PDAC
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)
1 other identifier
interventional
42
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Feb 2026
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 2, 2026
CompletedFirst Submitted
Initial submission to the registry
March 14, 2026
CompletedFirst Posted
Study publicly available on registry
March 18, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 14, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 26, 2028
March 18, 2026
March 1, 2026
1 year
March 14, 2026
March 14, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Incidence of dose-limiting toxicities (DLTs)
28 Days
Incidence and severity of treatment-emergent adverse events (TEAEs)
12 months
Maximum tolerated dose (MTD)
12 months
Secondary Outcomes (5)
Objective response rate (ORR) per RECIST v1.1
12 months
Disease control rate (DCR)
12 months
Duration of response (DOR)
24 months
Progression-free survival (PFS)
24 months
Overall survival (OS)
24 months
Study Arms (2)
EB-DNK101 (MSLN/MUC1 Dual-CAR NK)
EXPERIMENTALParticipants with PDAC whose tumors express MSLN and/or MUC1 per central IHC are assigned to Arm A. Interventions: Biological: EB-DNK101 dual-targeting CAR-NK cells (MSLN + MUC1); Drug: lymphodepleting chemotherapy (fludarabine + cyclophosphamide)
EB-DNK102 (CLDN18.2/MUC1 Dual-CAR NK)
EXPERIMENTALParticipants with PDAC whose tumors express CLDN18.2 and/or MUC1 per central IHC are assigned to Arm B.
Interventions
Allogeneic CAR-NK cells engineered with a dual-recognition CAR targeting MSLN and MUC1. Administered as an IV infusion on Day 0 (dose level dependent).
Allogeneic CAR-NK cells engineered with a dual-recognition CAR targeting CLDN18.2 and MUC1. Administered as an IV infusion on Day 0 (dose level dependent)
Example regimen: fludarabine (Days -5 to -3) and cyclophosphamide (Days -5 to -4) prior to CAR-NK infusion.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Beijing Biotechlead
Study Sites (1)
Peking University Shenzhen Hospital
Shenzhen, Guangdong, 518036, China
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Masking Details
- Open-label design due to the nature of cellular infusion and required safety monitoring.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 14, 2026
First Posted
March 18, 2026
Study Start
February 2, 2026
Primary Completion (Estimated)
February 14, 2027
Study Completion (Estimated)
June 26, 2028
Last Updated
March 18, 2026
Record last verified: 2026-03