Trials / Recruiting
RecruitingNCT07480928
Dual-Targeting 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)
- Status
- Recruiting
- Phase
- Phase 1 / Phase 2
- Study type
- Interventional
- Enrollment
- 42 (estimated)
- Sponsor
- Beijing Biotech · Industry
- Sex
- All
- Age
- 18 Years – 75 Years
- Healthy volunteers
- Not accepted
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.
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 (e.g., membrane-bound or secreted IL-15; example) and incorporate an inducible safety switch (e.g., iCasp9; example). * 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 (fludarabine + cyclophosphamide; example regimen) 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 (e.g., 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.
Conditions
Interventions
| Type | Name | Description |
|---|---|---|
| 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). |
| 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) |
| DRUG | Lymphodepleting chemotherapy (Flu/Cy) | Example regimen: fludarabine (Days -5 to -3) and cyclophosphamide (Days -5 to -4) prior to CAR-NK infusion. |
Timeline
- Start date
- 2026-02-02
- Primary completion
- 2027-02-14
- Completion
- 2028-06-26
- First posted
- 2026-03-18
- Last updated
- 2026-03-18
Locations
1 site across 1 country: China
Source: ClinicalTrials.gov record NCT07480928. Inclusion in this directory is not an endorsement.