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

NCT07627711 | Recruiting Phase 1 DMC

• 1 other identifier: ESSEN-PDAC-DNK-008
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 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.

Conditions

Pancreatic Ductal Adenocarcinoma (PDAC); Unresectable Locally Advanced; Metastatic Disease

Keywords

Pancreatic cancer; PDAC; CAR-NK; Natural killer cells; Mesothelin; MSLN; MUC1; Claudin 18.2; CLDN18.2; Adoptive cell therapy; Immunotherapy; Biomarker-guided

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 (3)

• Objective response rate (ORR) per RECIST v1.1

  12 months

• Disease control rate (DCR)

  12 months

• Duration of response (DOR)

  24 months

Study Arms (2)

Arm A: EB-DNK101 (MSLN/MUC1 Dual-CAR NK)

EXPERIMENTAL

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); Biological: EB-DNK102 dual-targeting CAR-NK cells (CLDN18.2 + MUC1); Drug: Lymphodepleting chemotherapy (Flu/Cy)

Arm B: EB-DNK102 (CLDN18.2/MUC1 Dual-CAR NK)

EXPERIMENTAL

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); Biological: EB-DNK102 dual-targeting CAR-NK cells (CLDN18.2 + MUC1); Drug: Lymphodepleting chemotherapy (Flu/Cy)

Interventions

EB-DNK101 dual-targeting CAR-NK cells (MSLN + MUC1) BIOLOGICAL

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).

Also known as: MSLN/MUC1 Dual-CAR NK, Dual-target CAR-NK (MSLN/MUC1)

Arm A: EB-DNK101 (MSLN/MUC1 Dual-CAR NK); Arm B: EB-DNK102 (CLDN18.2/MUC1 Dual-CAR NK)

EB-DNK102 dual-targeting CAR-NK cells (CLDN18.2 + MUC1) BIOLOGICAL

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).

Also known as: CLDN18.2/MUC1 Dual-CAR NK, Dual-target CAR-NK (CLDN18.2/MUC1)

Arm A: EB-DNK101 (MSLN/MUC1 Dual-CAR NK); Arm B: EB-DNK102 (CLDN18.2/MUC1 Dual-CAR NK)

Lymphodepleting chemotherapy (Flu/Cy) DRUG

fludarabine (Days -5 to -3) and cyclophosphamide (Days -5 to -4) prior to CAR-NK infusion.

Also known as: Fludarabine + Cyclophosphamide, Conditioning regimen

Arm A: EB-DNK101 (MSLN/MUC1 Dual-CAR NK); Arm B: EB-DNK102 (CLDN18.2/MUC1 Dual-CAR NK)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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) 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.

Sponsors & Collaborators

• Beijing Biotech: lead

Study Sites (1)

Peking University Shenzhen Hospital

Shenzhen, Guangdong, 518036, China

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis; Pancreatic Neoplasms

Interventions

fludarabine; Cyclophosphamide; Transplantation Conditioning

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Immunosuppression Therapy; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Central Study Contacts

Seni S Lu, Phd

CONTACT

+86 13076790030; Seni-Lu@beijing-biotech.com

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

Model Details: Biomarker-guided, multi-cohort study with a dose-escalation (Part 1) followed by dose-expansion (Part 2) within each cohort/arm.

Study Record Dates

• First Submitted: May 31, 2026
• First Posted: June 4, 2026
• Study Start: March 2, 2026
• Primary Completion (Estimated): April 14, 2027
• Study Completion (Estimated): March 17, 2028
• Last Updated: June 4, 2026

Record last verified: 2026-05

Locations

CN (1)