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

NCT06875076 | Recruiting Phase 2

• 1 other identifier: 24K353-001
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a prospective, multicenter, single-arm, Phase II clinical trial evaluating the efficacy and safety of ivonescimab (AK112) combined with chemotherapy in patients with pleural mesothelioma who failed prior immunotherapy, anti-angiogenic therapy, or chemotherapy. The regimen consists of a treatment phase (ivonescimab 20mg/kg combined with pemetrexed 500mg/m²/gemcitabine 1000mg/m²/vinorelbine 25mg/m² every 21 days for 4 cycles) followed by a maintenance phase (ivonescimab monotherapy 20mg/kg every 21 days until disease progression, intolerance, or up to 2 years).The trial plans to enroll 25 patients, with the primary endpoint being objective response rate (ORR). Secondary endpoints include progression-free survival (PFS), overall survival (OS), and safety profiles. Exploratory endpoints investigate biomarkers such as tertiary lymphoid structures, tumor-infiltrating lymphocytes, and macrophage polarization within the tumor microenvironment.

Conditions

Pretreated Pleural Mesothelioma

Outcome Measures

Primary Outcomes (1)

• objective response rate (ORR)

  From enrollment to the end of treatment at 3 months

Secondary Outcomes (3)

• progression-free survival (PFS)

  From enrollment to the end of treatment at 3 years

• overall survival (OS)

  From enrollment to the end of treatment at 5 years

• adverse effect

  From enrollment to the end of treatment at 3 years

Study Arms (1)

treatment

EXPERIMENTAL

ivonescimab 20mg/kg combined with pemetrexed 500mg/m²/gemcitabine 1000mg/m²/vinorelbine 25mg/m² every 21 days for 4 cycles followed by a maintenance phase (ivonescimab monotherapy 20mg/kg every 21 days until disease progression, intolerance, or up to 2 years).

Drug: Ivonescimab Combined With Chemotherapy

Interventions

Ivonescimab Combined With Chemotherapy DRUG

ivonescimab 20mg/kg combined with pemetrexed 500mg/m²/gemcitabine 1000mg/m²/vinorelbine 25mg/m² every 21 days for 4 cycles followed by a maintenance phase (ivonescimab monotherapy 20mg/kg every 21 days until disease progression, intolerance, or up to 2 years)

treatment

Eligibility Criteria

• Age: 18 Months - 75 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Asian ethnicity, aged 18-75, ECOG 0-1;
• Histologically confirmed malignant pleural mesothelioma;
• Progression after ≥1 and ≤2 prior systemic therapies (platinum-based chemotherapy, immunotherapy combinations, or anti-angiogenic therapy);
• ≥1 measurable lesion (modified RECIST 1.1);
• Adequate organ function (hemoglobin ≥90g/L, neutrophils ≥1.5×10⁹/L, creatinine clearance ≥50ml/min).

You may not qualify if:

• 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.
• 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.
• Current participation in other interventional clinical trials or receipt of investigational drugs/devices within 4 weeks prior to the first dose.
• 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.
• Prior systemic anti-angiogenic therapy combined with PD-1/PD-L1 inhibitors, including bevacizumab (and biosimilars), endostatin, small-molecule TKIs, ramucirumab, etc.
• Bleeding history ≥ Grade 3 (CTCAE v5.0) within 4 weeks prior to screening. History of solid organ or hematopoietic stem cell transplantation.
• Idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), or drug-induced pneumonitis.
• 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.
• History of myocarditis, cardiomyopathy, or malignant arrhythmia; acute myocardial infarction, unstable angina, or NYHA Class III-IV heart failure within 12 months.
• Uncontrolled hypertension (≥150/100 mmHg despite medication) or hypertensive crisis/encephalopathy.
• Active central nervous system (CNS) metastases or carcinomatous meningitis, except asymptomatic brain metastases.
• Active gastrointestinal bleeding, ulcers, or perforation risk (e.g., hematemesis ≥5 mL/day, melena, or hematochezia).
• Active autoimmune diseases requiring systemic treatment (e.g., immunosuppressants/corticosteroids) within 2 years. Replacement therapies (e.g., thyroid hormone, insulin) are allowed.
• Chronic corticosteroid use (\>10 mg/day prednisone equivalent). Inhaled corticosteroids for asthma/COPD or topical steroids are permitted.

Sponsors & Collaborators

• The First Hospital of Jilin University: lead

Study Sites (1)

Cancer center, First Hospital of Jilin University

Changchun, Jilin, 130000, China

RECRUITING

MeSH Terms

Interventions

Drug Therapy

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Ma

  The First Hospital of Jilin University

  STUDY CHAIR

Central Study Contacts

Kewei Ma

CONTACT

+86043188782222; makw@jlu.edu.cn

Ma, Professor

CONTACT

+86043188782222

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 8, 2025
• First Posted: March 13, 2025
• Study Start: March 8, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): December 1, 2029
• Last Updated: March 13, 2025

Record last verified: 2025-03

Locations

CN (1)