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RECRUITINGPhase 1 / Phase 2INTERVENTIONAL

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

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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.

Who May Be Eligible (Plain English)

Who May Qualify: - Age 18 to 75 years at the time of consent. - diagnosed by tissue sample (biopsy-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. - You should be able to carry out daily activities with 0 level of ability (ECOG 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. - expected to live at least 12 weeks. - Negative pregnancy test for participants of childbearing potential and agreement to use protocoldefined contraception. - Ability to understand and sign willing to sign a consent form Who Should NOT Join This Trial: - Active or untreated cancer that has spread to the brain, 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 conditions (where your immune system attacks your own body) requiring systemic immunosuppression within 14 days before lymphodepletion, or prednisone equivalent greater than 10 mg/day. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
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.

Treatments Being Tested

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.

Locations (1)

Peking University Shenzhen Hospital
Shenzhen, Guangdong, China