Inclusion Criteria:
1. Asian ethnicity, aged 18-75, ECOG 0-1;
2. Histologically confirmed malignant pleural mesothelioma;
3. Progression after ≥1 and ≤2 prior systemic therapies (platinum-based chemotherapy, immunotherapy combinations, or anti-angiogenic therapy);
4. ≥1 measurable lesion (modified RECIST 1.1);
5. Adequate organ function (hemoglobin ≥90g/L, neutrophils ≥1.5×10⁹/L, creatinine clearance ≥50ml/min).
Exclusion Criteria:
1. History of other malignancies within 5 years prior to enrollment, except cured basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma in situ with radical resection. Patients diagnosed with other malignancies or lung cancer more than 5 years prior to enrollment require pathological/cytological confirmation of recurrent lesions.
2. Radiologically confirmed tumor encasement of major blood vessels, necrosis, or cavitation with significant bleeding risk as judged by the investigator.
Tumor invasion of adjacent critical organs/vessels (e.g., heart/pericardium, trachea, esophagus, aorta, superior vena cava) or risk of esophageal-tracheal/pleural fistula.
3. Current participation in other interventional clinical trials or receipt of investigational drugs/devices within 4 weeks prior to the first dose.
4. Palliative local therapy for non-target lesions within 2 weeks prior to the first dose; non-specific immunomodulatory therapy (e.g., interleukin, interferon, thymosin, TNF-α, excluding IL-11 for thrombocytopenia) within 2 weeks; or herbal/Chinese patent medicines with anticancer indications within 1 week.
5. Prior systemic anti-angiogenic therapy combined with PD-1/PD-L1 inhibitors, including bevacizumab (and biosimilars), endostatin, small-molecule TKIs, ramucirumab, etc.
6. Bleeding history ≥ Grade 3 (CTCAE v5.0) within 4 weeks prior to screening. History of solid organ or hematopoietic stem cell transplantation.
7. Uncontrolled active infections (e.g., acute pneumonia) or acute exacerbation of chronic obstructive pulmonary disease within 1 month; active tuberculosis (TB) requiring clinical exclusion.
8. Idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), or drug-induced pneumonitis.
9. Major surgery or severe trauma within 30 days prior to the first dose, or planned major surgery within 30 days after the first dose; minor procedures (excluding PICC/port placement) within 3 days.
10. History of myocarditis, cardiomyopathy, or malignant arrhythmia; acute myocardial infarction, unstable angina, or NYHA Class III-IV heart failure within 12 months.
11. Uncontrolled hypertension (≥150/100 mmHg despite medication) or hypertensive crisis/encephalopathy.
12. Active central nervous system (CNS) metastases or carcinomatous meningitis, except asymptomatic brain metastases.
13. Active gastrointestinal bleeding, ulcers, or perforation risk (e.g., hematemesis ≥5 mL/day, melena, or hematochezia).
14. Active autoimmune diseases requiring systemic treatment (e.g., immunosuppressants/corticosteroids) within 2 years. Replacement therapies (e.g., thyroid hormone, insulin) are allowed.
15. Chronic corticosteroid use (\>10 mg/day prednisone equivalent). Inhaled corticosteroids for asthma/COPD or topical steroids are permitted.
16. Non-healing wounds or unhealed fractures.
17. Known hypersensitivity to any study drug component or severe hypersensitivity to monoclonal antibodies.
18. Reproductive criteria:
Female: Non-sterilized, non-menopausal, or unwilling to use contraception during and for 6 months post-treatment; positive pregnancy test or lactation.
Male: Non-sterilized or unwilling to use contraception during and for 6 months post-treatment.
19. HIV infection (positive HIV1/2 antibodies).
20. Untreated active hepatitis B (HBV DNA ≥1000 copies/mL). Patients with HBV DNA \<1000 copies/mL must receive antiviral therapy throughout the study.
21. Active HCV infection (positive HCV antibody with detectable HCV-RNA). Substance abuse or psychiatric disorders affecting compliance.
22. Live vaccination within 30 days prior to the first dose (inactivated vaccines allowed).
23. Other conditions that may interfere with study results, preclude full participation, or are deemed by the investigator to conflict with the subject's best interest.
