Dual-Target MSLN/FAP CAR-NK Cells for Pleural and Peritoneal Mesothelioma (DUAL-MESO-NK)

March 31, 2026 updated by: Beijing Biotech

A Phase 1/2, Open-Label, Nonrandomized, Biomarker-Guided Study of Locoregional Allogeneic Dual-Target Mesothelin (MSLN) / Fibroblast Activation Protein (FAP) Chimeric Antigen Receptor Natural Killer Cells in Adults With Unresectable, Recurrent, or Refractory Pleural or Peritoneal Mesothelioma

This example study evaluates locoregional allogeneic dual-target mesothelin/FAP CAR-NK cells in adults with unresectable, recurrent, or refractory pleural or peritoneal mesothelioma.

Eligible participants must have central confirmation of MSLN-positive tumor cells and FAP-positive tumorassociated stroma. The phase 1 portion defines the recommended phase 2 dose and schedule, and the phase 2 expansion explores preliminary antitumor activity, persistence, and biomarker response in pleural and peritoneal disease cohorts.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Mesothelioma remains a difficult serosal malignancy with limited curative options in recurrent or refractory disease. Mesothelin (MSLN) is a well-established tumor-associated antigen in malignant pleural mesothelioma and other serosal tumors, while fibroblast activation protein (FAP) is relevant in the dense, immunosuppressive stromal compartment that can limit immune-cell trafficking and persistence. For this example, MSLN is retained as the anchor target and FAP is selected as the preferred second target after assessment.

Screening includes central pathology review using archival or fresh tissue and, where available, complementary liquid-biopsy profiling. Participants enter this dual-target study only if both MSLN and FAP meet pre-specified positivity thresholds. If only one actionable target is confirmed, the participant should be considered for a companion single-target protocol rather than this draft dual target protocol.

The study is designed as an open-label, biomarker-guided phase 1/2 trial with two nonrandomized parallel cohorts defined by disease site: pleural mesothelioma and peritoneal mesothelioma.

Part 1uses staggered locoregional dose escalation to determine the recommended phase 2 dose and schedule.

Part 2 expands each cohort at the selected dose. Participants receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide before CAR-NK infusion. Delivery is intrapleural for pleural mesothelioma and intraperitoneal for peritoneal mesothelioma. A repeat infusion may be permitted between Day 21 and Day 35 if there is no dose-limiting toxicity and no radiographic progression.

Key objectives are to characterize safety, define the recommended dose and schedule, estimate preliminary antitumor activity, and study pharmacodynamic effects including CAR-NK persistence in blood and serosal fluid, changes in soluble mesothelin-related peptide (SMRP), ctDNA dynamics, and cytokine modulation within pleural or peritoneal compartments.

Study Type

Interventional

Enrollment (Estimated)

36

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 confirmed malignant pleural mesothelioma or malignant peritoneal mesothelioma; unresectable, recurrent, metastatic, or refractory disease.
  • Prior receipt of at least one standard systemic regimen for mesothelioma, or documented ineligibility, intolerance, or refusal of standard therapy considered reasonable by the investigator.
  • Central biomarker confirmation of MSLN-positive tumor cells and FAP-positive tumorassociated stroma at protocol-defined thresholds.
  • At least one measurable or evaluable lesion by cohort-appropriate imaging criteria.
  • ECOG performance status 0 to 1.
  • Adequate bone marrow, renal, hepatic, coagulation, cardiac, and pulmonary function to undergo lymphodepletion and locoregional cell infusion.
  • Safe procedural access for intrapleural or intraperitoneal administration, as applicable.
  • Recovery to Grade 1 or better from prior anticancer therapy toxicities, except alopecia, stable neuropathy, or controlled endocrine replacement.
  • Life expectancy of at least 12 weeks.
  • Negative pregnancy test for participants of childbearing potential and agreement to use protocoldefined contraception.
  • Ability to understand and sign informed consent

Exclusion Criteria:

  • Active or untreated CNS metastases, leptomeningeal disease, or uncontrolled seizures.
  • Uncontrolled bacterial, fungal, viral, or mycobacterial infection, including empyema, active pleural space infection, peritonitis, or uncontrolled HBV, HCV, or HIV infection.
  • Autoimmune disease requiring systemic immunosuppression within 14 days before lymphodepletion, or prednisone equivalent greater than 10 mg/day.
  • Clinically significant cardiovascular disease, uncontrolled arrhythmia, unstable angina, recent myocardial infarction, or other condition judged to increase infusion risk.
  • Severe interstitial lung disease, baseline oxygen requirement, or other pulmonary compromise making pleural therapy unsafe.
  • Bowel perforation risk, uncontrolled bowel obstruction, uncontrolled ascites, or any abdominal condition that makes intraperitoneal infusion unsafe in the peritoneal cohort.
  • Prior gene-modified cell therapy directed against MSLN or FAP within the protocol washout period, or active graft-versus-host disease after prior transplant.
  • Need for concurrent systemic anticancer therapy other than protocol-permitted supportive care.
  • Pregnancy or breastfeeding.
  • Any medical, psychiatric, social, or logistical condition that, in the investigator's judgment, could compromise safety, compliance, or interpretability of study 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: Pleural Mesothelioma Cohort
Participants with malignant pleural mesothelioma receive lymphodepleting chemotherapy followed by locoregional intrapleural infusion of the dual-target allogeneic CAR-NK product.
Biological: EB-MF-CAR-NK-01
Example investigational product: donor-derived allogeneic NK cells engineered to recognize both MSLN-positive tumor cells and FAPpositive stromal elements, manufactured under GMP
Other Names:
  • Mesothelin/FAP Dual-Target CAR-NK Cells
Drug: Fludarabine
Lymphodepleting chemotherapy administered before CAR-NK infusion
Other Names:
  • Flu
Drug: Cyclophosphamide
Lymphodepleting chemotherapy administered before CAR-NK infusion.
Other Names:
  • Cy
Experimental: Peritoneal Mesothelioma Cohort
Participants with malignant peritoneal mesothelioma receive the same conditioning backbone and product platform, but the CAR-NK cells are delivered by locoregional intraperitoneal administration.
Biological: EB-MF-CAR-NK-01
Example investigational product: donor-derived allogeneic NK cells engineered to recognize both MSLN-positive tumor cells and FAPpositive stromal elements, manufactured under GMP
Other Names:
  • Mesothelin/FAP Dual-Target CAR-NK Cells
Drug: Fludarabine
Lymphodepleting chemotherapy administered before CAR-NK infusion
Other Names:
  • Flu
Drug: Cyclophosphamide
Lymphodepleting chemotherapy administered before CAR-NK infusion.
Other Names:
  • Cy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of dose-limiting toxicities (DLTs) after first CAR-NK infusion
Time Frame: 28 days
28 days
ncidence and severity of treatment-emergent adverse events (TEAEs)
Time Frame: 12 months
ncidence and severity of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), cytokine release syndrome, neurotoxicity, pleuritis/peritonitis, infusion reactions, and on-target/off-tumor toxicities graded by CTCAE v5.0 and ASTCT crit
12 months
Determination of recommended phase 2 dose and schedule (RP2D/RP2S)
Time Frame: 6 months
6 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival (OS)
Time Frame: 24 months
24 months
Progression-free survival (PFS)
Time Frame: 24 months
24 months
Duration of response (DOR)
Time Frame: 24 months
24 months
Objective response rate (ORR) by modified RECIST for the pleural cohort and RECIST 1.1 for the peritoneal cohort
Time Frame: 12 months
12 months
Disease control rate (DCR) at 12 weeks
Time Frame: 12 weeks
12 weeks

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)

March 14, 2027

Study Completion (Estimated)

April 17, 2028

Study Registration Dates

First Submitted

March 17, 2026

First Submitted That Met QC Criteria

March 31, 2026

First Posted (Actual)

April 6, 2026

Study Record Updates

Last Update Posted (Actual)

April 6, 2026

Last Update Submitted That Met QC Criteria

March 31, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EB-CARNK-CRC-102

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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