Dual-target CAR-NK therapy targeting mesothelin and MUC1 for advanced pancreatic cancer

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 study will test whether two off-the-shelf CAR-NK cell therapies that target mesothelin or MUC1 are safe and can shrink tumors in people with advanced pancreatic cancer whose tumors express those proteins.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 42 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Beijing Biotech (industry)
• Drugs / interventions: CAR-T, chimeric antigen receptor, chemotherapy, cyclophosphamide, fludarabine
• Locations: 1 site (Shenzhen, Guangdong)
• Trial ID: NCT07480928 on ClinicalTrials.gov

What this trial studies

This Phase 1/2, open-label study uses a dose-escalation followed by dose-expansion design to define a recommended Phase 2 dose and estimate response rates in biomarker-defined cohorts. Two allogeneic CAR-NK products are tested: EB-DNK101 targeting MSLN and MUC1, and EB-DNK102 targeting CLDN18.2 and MUC1, both engineered for enhanced persistence and an inducible safety switch. Central immunohistochemistry on archival or fresh tumor tissue assigns participants to Arm A (MSLN/MUC1) or Arm B (CLDN18.2/MUC1), with lymphodepleting chemotherapy (fludarabine + cyclophosphamide) administered before intravenous CAR-NK infusion. Repeat infusions (up to three) may be permitted in the absence of prohibitive toxicity, with close monitoring for cytokine release syndrome, neurotoxicity, infusion reactions, and other adverse events while tumor response is assessed per RECIST.

Who should consider this trial

Good fit: Adults 18–75 with histologically confirmed unresectable locally advanced or metastatic PDAC who progressed after at least one prior systemic therapy, have measurable disease, ECOG 0–1, adequate organ function, and tumor expression of the target antigens by central IHC are ideal candidates.

Not a fit: Patients whose tumors lack the target antigen expression, who have poor performance status, inadequate organ function, or cannot tolerate lymphodepletion are unlikely to benefit from these therapies.

Why it matters

Potential benefit: If successful, this approach could provide an off-the-shelf cell therapy option that controls tumor growth and prolongs survival for patients with antigen-positive advanced pancreatic cancer.

How similar studies have performed: Prior CAR-T and early CAR-NK work against mesothelin and other solid tumor antigens have produced occasional responses, but dual-target, off-the-shelf CAR-NK therapy in PDAC remains largely experimental.

Eligibility criteria

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)

Where this trial is running

Shenzhen, Guangdong

• Peking University Shenzhen Hospital — Shenzhen, Guangdong, China (RECRUITING)

Study contacts

• Study coordinator: Seni S Lu, Phd

Conditions: Pancreatic Ductal Adenocarcinoma, Unresectable Locally Advanced or Metastatic Disease, Pancreatic cancer, PDAC, CAR-NK, Natural killer cells, Mesothelin, MSLN