Combining Ivonescimab with Chemotherapy for Mesothelioma Treatment

Efficacy and Safety of Ivonescimab (AK112) in Combination with Chemotherapy for the Treatment of Pretreated Pleural Mesothelioma: a Phase II Multicenter, Single-Arm Clinical Trial

This study is testing if adding a new drug called ivonescimab to chemotherapy can help people with pleural mesothelioma who haven't had success with other treatments.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 18 Months to 75 Months
• Sex: All
• Sponsor: The First Hospital of Jilin University (other)
• Drugs / interventions: bevacizumab, ramucirumab, chemotherapy, immunotherapy, prednisone, ivonescimab
• Locations: 1 site (Changchun, Jilin)
• Trial ID: NCT06875076 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness and safety of ivonescimab (AK112) in combination with chemotherapy for patients with pleural mesothelioma who have previously undergone treatment without success. The study follows a multicenter, single-arm design and aims to enroll 25 participants. Patients will receive ivonescimab alongside chemotherapy agents for four cycles, followed by maintenance therapy with ivonescimab alone. The primary goal is to assess the objective response rate, while secondary goals include progression-free survival and overall survival metrics.

Who should consider this trial

Good fit: Ideal candidates are Asian individuals aged 18-75 with histologically confirmed malignant pleural mesothelioma who have experienced disease progression after one to two prior systemic therapies.

Not a fit: Patients with a history of other malignancies within the past five years or those with significant tumor encasement of major blood vessels may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new therapeutic option for patients with advanced pleural mesothelioma who have limited treatment choices.

How similar studies have performed: While this approach is novel in the context of pleural mesothelioma, similar combinations of immunotherapy and chemotherapy have shown promise in other cancer types.

Eligibility criteria

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.

Where this trial is running

Changchun, Jilin

• Cancer center, First Hospital of Jilin University — Changchun, Jilin, China (RECRUITING)

Study contacts

• Study coordinator: Kewei Ma

Conditions: Pretreated Pleural Mesothelioma