Mesothelioma
Conditions
Brief summary
This is a prospective, single-arm, multicenter, phase II clinical trial designed to evaluate the efficacy and safety of iparomlimab and tuvoraleimab in combination with bevacizumab and chemotherapy as first-line treatment for advanced mesothelioma.
Interventions
DRUGIparomlimab and Tuvoraleimab injection+Bevacizumab+Pemetrexed+Cisplatin
Iparomlimab and Tuvoraleimab: 5 mg/kg each, on Day 1, intravenous injection, every 3 weeks (Q3W); Bevacizumab: 7.5 mg/kg, on Day 1, intravenous infusion, Q3W; Pemetrexed: 500 mg/m², on Day 1, intravenous infusion, Q3W; Platinum-based agent: either Cisplatin 75 mg/m² on Day 1, intravenous infusion, Q3W, or Carboplatin AUC = 5 on Day 1, intravenous infusion, Q3W; the specific agent is at the investigator's discretion.
Sponsors
Fudan University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Both male and female patients aged 18 to 75 years (inclusive). * Histopathologically confirmed advanced mesothelioma. * No prior systemic therapy. * At least one measurable lesion according to mRECIST 1.1 and RECIST 1.1 criteria. * Life expectancy ≥ 3 months. * Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2. * Adequate major organ function, meeting the following laboratory criteria: Hemoglobin (Hb) ≥ 90 g/L.White blood cell count ≥ 3.0 × 10⁹/L.Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L.Platelet count (PLT) ≥ 100 × 10⁹/L.Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN).Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN.Serum creatinine clearance (CrCl) ≥ 50 mL/min (calculated by the Cockcroft-Gault formula). Coagulation function: international normalized ratio (INR) ≤ 1.5 × ULN, and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN. * Subjects agree to use effective contraceptive methods from the time of signing informed consent until 120 days after the last dose of study drug. Female subjects of childbearing potential must have a negative urine pregnancy test within 7 days before the start of treatment and must be non-lactating. A female patient is considered to have childbearing potential if she has experienced menarche, has not reached a postmenopausal state (≥12 consecutive months of amenorrhea with no identified cause other than menopause), and has not undergone sterilization surgery (e.g., hysterectomy, bilateral tubal ligation, or bilateral oophorectomy). * Subjects voluntarily participate in this study, sign the informed consent form, demonstrate good compliance, and agree to cooperate with follow-up.
Exclusion criteria
* Prior systemic anti-tumor therapy, except for patients who relapsed more than six months after completion of adjuvant chemotherapy. * Known history of hypersensitivity to macromolecular protein preparations, or contraindication or allergy to any component of iparomlimab and tuvoraleimab, bevacizumab, pemetrexed, or platinum-based agents. * Major surgery (excluding diagnostic laparoscopy; local surgical treatment of isolated lesions is acceptable) within 28 days before the first dose. * History of allogeneic tissue/solid organ transplantation. * Presence of any condition requiring systemic corticosteroids (\>10 mg daily prednisone or equivalent) or other immunosuppressive agents (e.g., cyclophosphamide, azathioprine, methotrexate, thalidomide, TNF-α inhibitors) within 2 weeks before the first dose. Topical corticosteroids, nasal sprays, and inhaled steroids are permitted. Systemic corticosteroids for prophylaxis of contrast allergy are allowed. * Active or potentially relapsing autoimmune disease, with the following exceptions: vitiligo, alopecia, psoriasis, or eczema not requiring systemic treatment; hypothyroidism due to autoimmune thyroiditis requiring only stable dose of hormone replacement therapy; type I diabetes mellitus requiring only stable dose of insulin replacement therapy. * Other active malignancy within the past 5 years, except for cured locally treatable cancers (e.g., basal or squamous cell skin cancer, superficial bladder cancer, or in situ cervical or breast cancer) and breast cancer that has not recurred for \>3 years after radical surgery. * History of interstitial lung disease and/or pneumonitis, or pulmonary hypertension. * Symptomatic, untreated, or clinically unstable brain metastases or leptomeningeal metastases. * Poorly controlled hypertension (systolic blood pressure \>150 mmHg and/or diastolic blood pressure \>100 mmHg) or poorly controlled diabetes despite standard treatment, or uncontrolled symptomatic arrhythmia. * Thromboembolic events (e.g., cerebrovascular accident including transient ischemic attack, cerebral hemorrhage, cerebral infarction, or pulmonary embolism) within 6 months before the start of study treatment. * Myocardial infarction, severe/unstable angina, or symptomatic congestive heart failure (New York Heart Association \[NYHA\] class III or IV) within the past 12 months. * Participation in another clinical trial within the past 60 days or during the study treatment period. * Known active HIV, HBV, or HCV infection. * Any other condition that, in the investigator's judgment, may interfere with the conduct of the study or the interpretation of the results, or renders the patient unsuitable for enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | up to 2 years | Defined as the percentage of subjects achieving complete response (CR) or partial response (PR). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease control rate (DCR) | up to 2 years | Defined as the percentage of participants in the analysis population who achieved Complete Response, Partial Response, or Stable Disease. |
| Duration of Response (DoR) | up to 2 years | Defined as the time from the first tumor assessment showing response (complete response \[CR\] or partial response \[PR\]) to disease progression or death, whichever occurs first, in patients who achieve CR or PR. |
| Progression-Free Survival (PFS) | up to 2 years | Defined as the time from enrollment to the date of first documented tumor progression (as assessed per mRECIST 1.1 and RECIST v1.1 criteria, regardless of whether treatment is continued) or death from any cause, whichever occurs first. |
| Overall Survival (OS) | up to 2 years | Defined as the time from the initiation of treatment until death from any cause. |
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | up to 2 years | Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 |
Countries
China
Contacts
CONTACTxin Liu
Outcome results
None listed