Dual-target mesothelin and FAP CAR-NK therapy for pleural and peritoneal mesothelioma
Official title: 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
Run by Beijing Biotech · NCT07510815 · Data updated 2026-11-12
This trial will try locoregional dual-target CAR-NK cells that attack mesothelin on tumor cells and FAP in the tumor stroma in adults with unresectable, recurrent, or refractory pleural or peritoneal mesothelioma who test positive for both markers.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Enrollment | 36 (estimated) |
| Sponsor | Beijing Biotech Industry-sponsored |
| Drugs / interventions | prednisone, chemotherapy, cyclophosphamide, fludarabine |
| Locations | 1 site (Shenzhen, Guangdong) |
| Status | Recruiting |
| Started | March 2, 2026 |
| Main results expected | March 14, 2027 |
| Study ends | April 17, 2028 |
| Registry record updated | April 6, 2026 |
| Trial ID | NCT07510815 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a good fit
Adults 18–75 years with unresectable, recurrent, metastatic, or refractory pleural or peritoneal mesothelioma, ECOG 0–1, who have received at least one prior systemic regimen (or are ineligible) and have central confirmation of MSLN-positive tumor cells and FAP-positive stroma are ideal candidates.
✕Probably not a fit
Patients whose tumors lack MSLN or whose stroma lacks FAP, those unable to tolerate lymphodepletion, or those without safe intrapleural/intraperitoneal access are unlikely to benefit from this protocol.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
What this trial studies
This open-label phase 1/2 trial uses centrally confirmed biomarkers to enroll adults with pleural or peritoneal mesothelioma whose tumor cells express mesothelin (MSLN) and whose stromal tissue expresses fibroblast activation protein (FAP). Part 1 uses staggered intrapleural or intraperitoneal dose escalation to find the recommended phase 2 dose and schedule following lymphodepleting chemotherapy with fludarabine and cyclophosphamide. Part 2 expands separate pleural and peritoneal cohorts at the selected dose to explore preliminary antitumor activity, cellular persistence, and biomarker responses. All participants undergo central pathology confirmation of MSLN and FAP using archival or fresh tissue, with optional complementary liquid biopsy profiling where available.
Why it matters
Potential benefit: If successful, the therapy could improve local tumor control and prolong benefit by targeting both tumor cells and the supportive, immunosuppressive stroma.
How similar studies have gone: MSLN-targeted therapies have shown some promising but limited activity in mesothelioma, while combining a stromal target like FAP with locally delivered CAR-NK cells is a relatively new approach with limited clinical precedent.
Who can join: the full rules
Show full inclusion / exclusion criteria
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.
Where it's running
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Peking University Shenzhen Hospital
Shenzhen, Guangdong, China Recruiting
Study contacts
- Study coordinator: Seni S Lu, Phd
- Email: Seni-Lu@beijing-biotech.com
- Phone: +86 13076790030
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How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.