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.
• 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