An Open-label, Single-arm Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Profile, and Preliminary Efficacy of KT032 Cell Injection in Patients With Mesothelin-positive Advanced Solid Tumors.

1. Aged 18 to 75 years (inclusive), any gender;

2. Histopathologically confirmed diagnosis of advanced solid tumors (including but not limited to ovarian cancer, mesothelioma, colon cancer, etc.), with peritoneal or intraperitoneal metastasis as the primary disease manifestation;

3. Progression or intolerance to prior systemic standard-of-care treatment according to guidelines (systemic therapy includes but is not limited to systemic chemotherapy, molecular targeted therapy, etc.), and unsuitable for surgery or local treatment (including ablation therapy, interventional therapy, and radiotherapy); specifically: Ovarian cancer: Recurrence during or within 6 months after second-line or later platinum-based chemotherapy; Mesothelioma: Failure of, intolerance to, or ineligibility for at least first-line therapy; Colon cancer: Failure of, intolerance to, or ineligibility for at least third-line therapy;

1. Ovarian cancer: Progression, intolerance, or ineligibility after second-line standard therapy including carboplatin ± paclitaxel/albumin-bound paclitaxel/docetaxel/pegylated liposomal doxorubicin;

2. Advanced colon cancer: Progression, intolerance, or ineligibility after third-line standard therapy including cetuximab ± irinotecan/regorafenib/fruquintinib/trifluridine/tipiracil;

3. Mesothelioma: Progression, intolerance, or ineligibility after first-line standard therapy with pemetrexed combined with cisplatin/carboplatin;

4. Presence of at least one measurable lesion per RECIST 1.1 criteria;

5. MSLN expression positivity in tumor tissue detected by immunohistochemistry (IHC), defined as IHC ≥2+ (i.e., ≥26% positive tumor cells stained); subjects must undergo fresh tumor tissue biopsy; if biopsy is not feasible, at least 5 archived tumor tissue slides collected within one year must be provided (if multiple tumor tissue collections exist, the most recent sample is preferred);

6. ECOG performance status 0-1 (see Appendix 1) and estimated life expectancy \>12 weeks;

7. Adequate organ function with all following laboratory results prior to enrollment:

Hematology: Absolute neutrophil count (ANC) ≥1.5×10⁹/L (growth factor support allowed, but must not have received within 7 days prior to laboratory testing); Absolute lymphocyte count (ALC) ≥0.7×10⁹/L; Platelets ≥100×10⁹/L (no transfusion support within 7 days prior to laboratory testing); Hemoglobin ≥90 g/L (no RBC transfusion within 7 days prior to laboratory testing; recombinant human erythropoietin allowed); Hepatic function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×upper limit of normal (ULN); Total serum bilirubin ≤2×ULN; ALT and AST may be extended to ≤5×ULN if abnormalities are determined by the investigator to be due to disease (e.g., hepatic metastases or biliary obstruction) or Gilbert's syndrome; Renal function: Creatinine clearance (CrCl) ≥50 mL/min calculated by Cockcroft-Gault formula; Coagulation function: Fibrinogen ≥1.0 g/L; Activated partial thromboplastin time ≤1.5×ULN; Prothrombin time (PT) ≤1.5×ULN; Oxygen saturation \>91% (on room air); Left ventricular ejection fraction (LVEF) ≥50%;

8. Recovery from all toxicities related to prior treatment to acceptable baseline status, or recovery to normal or Grade 1 per NCI CTCAE 5.0, as determined by the investigator; except for toxicities not expected to increase safety risk of subsequent investigational product infusion, such as alopecia, vitiligo, etc.;

9. Agreement by subjects and their partners to use effective contraceptive methods (excluding rhythm method) from the time of informed consent signature until one year after CAR-T cell infusion;

10. Written informed consent on IRB/IEC-approved consent form obtained personally from the subject prior to initiation of any screening procedures.

What this study is about