Pretreated Pleural MesotheliomaPhase 2NCT06875076
Multicenter Single-Arm Study of Ivonescimab (AK112) Combined with Chemotherapy in Pretreated Pleural Mesothelioma
A Phase 2 study testing Ivonescimab Combined With Chemotherapy in people with Pretreated Pleural Mesothelioma, run by The First Hospital of Jilin University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 months
- Conditions the study is for
- Pretreated Pleural Mesothelioma
- What is being tested?
- Ivonescimab Combined With Chemotherapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteChina
- Study dates
- 8 Mar 2025to Dec 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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).
Who cannot join
- 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.
Show all 26Show fewer
- Bleeding history ≥ Grade 3 (CTCAE v5.0) within 4 weeks prior to screening. History of solid organ or hematopoietic stem cell transplantation.
- Uncontrolled active infections (e.g., acute pneumonia) or acute exacerbation of chronic obstructive pulmonary disease within 1 month; active tuberculosis (TB) requiring clinical exclusion.
- 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.
- Non-healing wounds or unhealed fractures.
- Known hypersensitivity to any study drug component or severe hypersensitivity to monoclonal antibodies.
- 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.
- HIV infection (positive HIV1/2 antibodies).
- Untreated active hepatitis B (HBV DNA ≥1000 copies/mL). Patients with HBV DNA <1000 copies/mL must receive antiviral therapy throughout the study.
- Active HCV infection (positive HCV antibody with detectable HCV-RNA). Substance abuse or psychiatric disorders affecting compliance.
- Live vaccination within 30 days prior to the first dose (inactivated vaccines allowed).
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Ma, Professor contact
China1 site, 1 recruiting
- Recruiting
Cancer center, First Hospital of Jilin University
Changchun, Jilin, 130000
Kewei Ma, +86043188782222, makw@jlu.edu.cn
About this study
Official title: 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 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.
Read the detailed description
Study Protocol Overview This is a prospective, multicenter, single-arm Phase II clinical trial evaluating the efficacy and safety of ivonescimab (AK112) combined with chemotherapy in pretreated pleural mesothelioma patients who failed prior immunotherapy, anti-angiogenic therapy, or chemotherapy. Utilizing a Simon two-stage design, the study plans to enroll 25 participants. The primary endpoint is objective response rate (ORR), with secondary endpoints including 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 in the tumor microenvironment.
Treatment Regimen Treatment Phase: Ivonescimab (20mg/kg, Q3W) combined with chemotherapy (pemetrexed 500mg/m², gemcitabine 1000mg/m², or vinorelbine 25mg/m²) for 4 cycles.
Maintenance Phase: Ivonescimab monotherapy (20mg/kg, Q3W) until disease progression, intolerance, or up to 2 years.
Inclusion Criteria 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).
Exclusion Criteria History of other malignancies within 5 years (except cured skin carcinoma or in situ cancer); Tumor encasing critical vasculature or with necrosis/cavitation posing bleeding risks; Active hepatitis B (untreated HBV DNA≥1000 copies/ml), HIV, or HCV infection; Active autoimmune disease requiring systemic treatment within 2 years; Participation in other interventional studies within 4 weeks prior to enrollment.
Sample Size Calculation Based on Simon's two-stage design, assuming ORR improvement from 6% to 25% (α=0.05, power=80%). Stage 1 enrolls 9 patients; if ≤2 responses occur, the trial stops. Otherwise, Stage 2 proceeds, totaling 25 participants.
Study Endpoints Primary: Objective response rate (ORR); Secondary: PFS, OS, disease control rate (DCR), duration of response (DoR), safety; Exploratory: Tertiary lymphoid structures (CD3/CD20/CD21), tumor-infiltrating lymphocytes (CD4/FOXP3), macrophage polarization (M1:M2).
- Conditions
- Pretreated Pleural Mesothelioma
- Being tested
- Ivonescimab Combined With Chemotherapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ivonescimab Combined With ChemotherapyDrug
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)
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: Ivonescimab Combined With Chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
objective response rate (ORR)
Measured: From enrollment to the end of treatment at 3 months
Secondary outcomes (3)
progression-free survival (PFS)
Measured: From enrollment to the end of treatment at 3 years
overall survival (OS)
Measured: From enrollment to the end of treatment at 5 years
adverse effect
Measured: From enrollment to the end of treatment at 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2025
- Study start8 Mar 2025 (estimated)
- Primary completionJan 2028 (estimated)
- Study completionDec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pretreated Pleural MesotheliomaStudies of the same condition, open and under way.
- More trials run by The First Hospital of Jilin UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The First Hospital of Jilin University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kewei Ma, The First Hospital of Jilin University
- Investigators
- Ma, Study chair, The First Hospital of Jilin University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06875076
- Sponsor's protocol ID
- 24K353-001
- Status last verified
- Mar 2025
- First submitted
- 8 Mar 2025
- Last updated
- 13 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06875076
- Acronym / sponsor ID
- 24K353-001
- Conditions
- Pretreated Pleural Mesothelioma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- The First Hospital of Jilin UniversityUniversity, hospital or other
- Study start
- 8 Mar 2025 (estimated)
- Primary completion
- Jan 2028 (estimated)
- Study completion
- Dec 2029 (estimated)
- First posted
- 13 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Study Protocol Overview This is a prospective, multicenter, single-arm Phase II clinical trial evaluating the efficacy and safety of ivonescimab (AK112) combined with chemotherapy in pretreated pleural mesothelioma patients who failed prior immunotherapy, anti-angiogenic therapy, or chemotherapy. Utilizing a Simon two-stage design, the study plans to enroll 25 participants. The primary endpoint is objective response rate (ORR), with secondary endpoints including 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 in the tumor microenvironment.
Treatment Regimen Treatment Phase: Ivonescimab (20mg/kg, Q3W) combined with chemotherapy (pemetrexed 500mg/m², gemcitabine 1000mg/m², or vinorelbine 25mg/m²) for 4 cycles.
Maintenance Phase: Ivonescimab monotherapy (20mg/kg, Q3W) until disease progression, intolerance, or up to 2 years.
Inclusion Criteria 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).
Exclusion Criteria History of other malignancies within 5 years (except cured skin carcinoma or in situ cancer); Tumor encasing critical vasculature or with necrosis/cavitation posing bleeding risks; Active hepatitis B (untreated HBV DNA≥1000 copies/ml), HIV, or HCV infection; Active autoimmune disease requiring systemic treatment within 2 years; Participation in other interventional studies within 4 weeks prior to enrollment.
Sample Size Calculation Based on Simon's two-stage design, assuming ORR improvement from 6% to 25% (α=0.05, power=80%). Stage 1 enrolls 9 patients; if ≤2 responses occur, the trial stops. Otherwise, Stage 2 proceeds, totaling 25 participants.
Study Endpoints Primary: Objective response rate (ORR); Secondary: PFS, OS, disease control rate (DCR), duration of response (DoR), safety; Exploratory: Tertiary lymphoid structures (CD3/CD20/CD21), tumor-infiltrating lymphocytes (CD4/FOXP3), macrophage polarization (M1:M2).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| treatment | Experimental | Drug: Ivonescimab Combined With Chemotherapyivonescimab 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). |
Who may qualify
- Ages
- 18 to 75 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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).
Key exclusion criteria (26 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ivonescimab Combined With Chemotherapyivonescimab 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 | treatment |
Primary outcome
objective response rate (ORR)
Time frame: From enrollment to the end of treatment at 3 months
3 secondary outcomes
progression-free survival (PFS)
Time frame: From enrollment to the end of treatment at 3 years
overall survival (OS)
Time frame: From enrollment to the end of treatment at 5 years
adverse effect
Time frame: From enrollment to the end of treatment at 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2025.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ma, Professor contact
Ma study chair
The First Hospital of Jilin University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ivonescimab Combined With Chemotherapy in people with Pretreated Pleural Mesothelioma, run by The First Hospital of Jilin University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kewei Ma (+86043188782222, makw@jlu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
objective response rate (ORR) (time frame: From enrollment to the end of treatment at 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2025.