NCT07510815

Dual-Target MSLN/FAP CAR-NK Cells for Pleural and Peritoneal Mesothelioma

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

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 36 (estimated)
• Sponsor: Beijing Biotech · Industry
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

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.

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.

Conditions

• Malignant Pleural Mesotheliomas

Interventions

Type	Name	Description
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
DRUG	Fludarabine	Lymphodepleting chemotherapy administered before CAR-NK infusion
DRUG	Cyclophosphamide	Lymphodepleting chemotherapy administered before CAR-NK infusion.

Timeline

• Start date: 2026-03-02
• Primary completion: 2027-03-14
• Completion: 2028-04-17
• First posted: 2026-04-06
• Last updated: 2026-04-06

Locations

1 site across 1 country: China