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

May 31, 2026 updated by: Beijing Biotech

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)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

  • Rationale: PDAC is characterized by aggressive biology, antigen heterogeneity, and an immunosuppressive tumor microenvironment. Dual-targeting CAR designs aim to reduce antigen-escape by enabling recognition of either target antigen on tumor cells.
  • Investigational products: Two off-the-shelf (allogeneic) CAR-NK products are evaluated. EB-DNK101 targets MSLN and MUC1. EB-DNK102 targets CLDN18.2 and MUC1. Both products are engineered to enhance persistence and incorporate an inducible safety switch .
  • Target assessment and cohort assignment: Tumor tissue (archival or fresh biopsy) is tested centrally by immunohistochemistry (IHC) for MSLN, MUC1, and CLDN18.2. Participants are assigned to Arm A (MSLN/MUC1) or Arm B (CLDN18.2/MUC1) based on predefined positivity thresholds. If more than one cohort is eligible, assignment prioritizes the strongest antigen expression and product availability.
  • Conditioning and administration: Participants receive lymphodepleting chemotherapy followed by intravenous infusion of the assigned CAR-NK product.

Repeat infusions (up to 3 total) may be permitted in the absence of prohibitive toxicity and with at least stable disease. Safety monitoring: Participants are monitored closely for cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), infusion reactions, and other adverse events.

Dose-limiting toxicities (DLTs) are assessed during the first 28 days after first infusion.

  • Efficacy and biomarker assessments: Tumor response is assessed by imaging (RECIST v1.1) at regular intervals (every 8 weeks). Exploratory endpoints include CAR-NK expansion/persistence, cytokine profiling, and association of antigen density with response.
  • Target down-selection plan: After completion of Part 1 and an initial subset of Part 2 expansion participants, an internal scientific review compares antigen prevalence, manufacturability, safety, and preliminary activity across cohorts to prioritize the lead dual-target construct for subsequent confirmatory development.

Study Type

Interventional

Enrollment (Estimated)

42

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Shenzhen, Guangdong, China, 518036

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A: EB-DNK101 (MSLN/MUC1 Dual-CAR NK)
Participants with PDAC whose tumors express MSLN and/or MUC1 per central IHC are assigned to Arm A.
Biological: EB-DNK101 dual-targeting CAR-NK cells (MSLN + MUC1)
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).
Other Names:
  • MSLN/MUC1 Dual-CAR NK, Dual-target CAR-NK (MSLN/MUC1)
Biological: EB-DNK102 dual-targeting CAR-NK cells (CLDN18.2 + MUC1)
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).
Other Names:
  • CLDN18.2/MUC1 Dual-CAR NK, Dual-target CAR-NK (CLDN18.2/MUC1)
Drug: Lymphodepleting chemotherapy (Flu/Cy)

fludarabine (Days -5 to -3) and cyclophosphamide (Days -5 to

-4) prior to CAR-NK infusion.

Other Names:
  • Fludarabine + Cyclophosphamide, Conditioning regimen
Experimental: Arm B: EB-DNK102 (CLDN18.2/MUC1 Dual-CAR NK)
Participants with PDAC whose tumors express CLDN18.2 and/or MUC1 per central IHC are assigned to Arm B.
Biological: EB-DNK101 dual-targeting CAR-NK cells (MSLN + MUC1)
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).
Other Names:
  • MSLN/MUC1 Dual-CAR NK, Dual-target CAR-NK (MSLN/MUC1)
Biological: EB-DNK102 dual-targeting CAR-NK cells (CLDN18.2 + MUC1)
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).
Other Names:
  • CLDN18.2/MUC1 Dual-CAR NK, Dual-target CAR-NK (CLDN18.2/MUC1)
Drug: Lymphodepleting chemotherapy (Flu/Cy)

fludarabine (Days -5 to -3) and cyclophosphamide (Days -5 to

-4) prior to CAR-NK infusion.

Other Names:
  • Fludarabine + Cyclophosphamide, Conditioning regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum tolerated dose (MTD)
Time Frame: 12 months
12 months
Incidence of dose-limiting toxicities (DLTs)
Time Frame: 28 Days
28 Days
Incidence and severity of treatment-emergent adverse events (TEAEs)
Time Frame: 12 months
12 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Disease control rate (DCR)
Time Frame: 12 months
12 months
Objective response rate (ORR) per RECIST v1.1
Time Frame: 12 months
12 months
Duration of response (DOR)
Time Frame: 24 months
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing Biotech

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 2, 2026

Primary Completion (Estimated)

April 14, 2027

Study Completion (Estimated)

March 17, 2028

Study Registration Dates

First Submitted

May 31, 2026

First Submitted That Met QC Criteria

May 31, 2026

First Posted (Actual)

June 4, 2026

Study Record Updates

Last Update Posted (Actual)

June 4, 2026

Last Update Submitted That Met QC Criteria

May 31, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ESSEN-PDAC-DNK-008

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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