Multicenter Single-Arm Study of Ivonescimab (AK112) Combined with Chemotherapy in Pretreated Pleural Mesothelioma

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, creatinineclearance ≥50ml/min).

Exclusion Criteria:

1. History of other malignancies within 5 years prior to enrollment, except cured basalcell carcinoma, squamous cell carcinoma of the skin, or carcinoma in situ withradical resection. Patients diagnosed with other malignancies or lung cancer morethan 5 years prior to enrollment require pathological/cytological confirmation ofrecurrent lesions.

2. Radiologically confirmed tumor encasement of major blood vessels, necrosis, orcavitation 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 ofesophageal-tracheal/pleural fistula.

3. Current participation in other interventional clinical trials or receipt ofinvestigational drugs/devices within 4 weeks prior to the first dose.

4. Palliative local therapy for non-target lesions within 2 weeks prior to the firstdose; non-specific immunomodulatory therapy (e.g., interleukin, interferon,thymosin, TNF-α, excluding IL-11 for thrombocytopenia) within 2 weeks; orherbal/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. Historyof solid organ or hematopoietic stem cell transplantation.

7. Uncontrolled active infections (e.g., acute pneumonia) or acute exacerbation ofchronic obstructive pulmonary disease within 1 month; active tuberculosis (TB)requiring clinical exclusion.

8. Idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitisobliterans), or drug-induced pneumonitis.

9. Major surgery or severe trauma within 30 days prior to the first dose, or plannedmajor surgery within 30 days after the first dose; minor procedures (excludingPICC/port placement) within 3 days.

10. History of myocarditis, cardiomyopathy, or malignant arrhythmia; acute myocardialinfarction, unstable angina, or NYHA Class III-IV heart failure within 12 months.

11. Uncontrolled hypertension (≥150/100 mmHg despite medication) or hypertensivecrisis/encephalopathy.

12. Active central nervous system (CNS) metastases or carcinomatous meningitis, exceptasymptomatic brain metastases.

13. Active gastrointestinal bleeding, ulcers, or perforation risk (e.g., hematemesis ≥5mL/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). Inhaledcorticosteroids 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 tomonoclonal antibodies.

18. Reproductive criteria: Female: Non-sterilized, non-menopausal, or unwilling to use contraception during andfor 6 months post-treatment; positive pregnancy test or lactation. Male: Non-sterilized or unwilling to use contraception during and for 6 monthspost-treatment.

19. HIV infection (positive HIV1/2 antibodies).

20. Untreated active hepatitis B (HBV DNA ≥1000 copies/mL). Patients with HBV DNA <1000copies/mL must receive antiviral therapy throughout the study.

21. Active HCV infection (positive HCV antibody with detectable HCV-RNA). Substanceabuse or psychiatric disorders affecting compliance.

22. Live vaccination within 30 days prior to the first dose (inactivated vaccinesallowed).

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.