Peritoneal Mesothelioma, First-line Therapy
Conditions
Keywords
MPeM, Immunotherapy, CTLA4 inhibitor
Brief summary
This is a prospective, multicenter, single-arm, Phase II clinical study evaluating the efficacy and safety of sintilimab in combination with ipilimumab N01 and bevacizumab as first-line treatment in patients with unresectable malignant peritoneal mesothelioma. Eligible patients will receive sintilimab plus ipilimumab N01 and bevacizumab until disease progression, death, unacceptable toxicity, withdrawal of informed consent, initiation of a new anti-tumor therapy, or other protocol-defined reasons, with a maximum treatment duration of 24 months. The primary endpoint is progression-free survival (PFS).
Interventions
DRUGSintilimab
Sintilimab: 200 mg IV, D1 and D22, Q3W (Day 1 of every 3 weeks) Treatment continues until disease progression, death, unacceptable toxicity, withdrawal of informed consent, initiation of a new anti-tumor therapy, or other protocol-defined reasons; maximum treatment duration is 24 months.
DRUGIpilimumab N01
Ipilimumab N01: 1 mg/kg IV, D1, Q6W (Day 1 of every 6 weeks) Treatment continues until disease progression, death, unacceptable toxicity, withdrawal of informed consent, initiation of a new anti-tumor therapy, or other protocol-defined reasons; maximum treatment duration is 24 months.
DRUGBevacizumab
Bevacizumab: 15 mg/kg IV, D1 and D22, Q3W (Day 1 of every 3 weeks) Treatment continues until disease progression, death, unacceptable toxicity, withdrawal of informed consent, initiation of a new anti-tumor therapy, or other protocol-defined reasons; maximum treatment duration is 24 months.
Sponsors
Fudan University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have fully understood the study and voluntarily signed the informed consent; * Age≥ 18 years, gender not restricted; * Eastern Cooperative Oncology Group (ECOG) performance status (PS) score 0-1, with an expected survival period of more than 3 months; * Metastatic or locally advanced unresectable peritoneal mesothelioma confirmed by pathology or histology; * At least one evaluable lesion (according to RECIST 1.1 criteria); * Thyroid function, thyroid stimulating hormone (TSH) ≤ upper limit of normal (ULN), subjects with asymptomatic abnormalities of T3, FT3, or FT4 are eligible. * Adequately controlled blood pressure. * Have not received any anti-tumor therapy (including chemotherapy, targeted therapy, immunotherapy, etc.) for unresectable advanced or metastatic peritoneal mesothelioma; * Laboratory test data within 7 days before screening (including 7 days) should meet the following requirements: neutrophil count ≥ 1.5×109/L, platelet count ≥ 75×109/L, hemoglobin ≥ 9g/dL, total serum bilirubin ≤ 3 times the upper limit of normal (ULN); ALT and AST ≤ 5 x ULN; albumin ≥ 28g/L; serum creatinine (Cr) ≤ 1.5 x ULN or creatinine clearance rate (CCr) ≥ 50ml/min; INR≤1.5 x ULN, APTT≤1.5 x ULN; urinalysis showing urine protein \< 2+, for subjects with urine protein ≥ 2+ at baseline, a 24-hour urine collection must be performed and the 24-hour urine protein must be \< 1 g. * Fertile female must have a negative serum pregnancy test within 3 days before first dose. * Fertile female and male patients with female partners of childbearing potential must use a highly effective contraceptive method (annual failure rate \< 1 %) from 7 days before first dose until 120 days after the last dose.
Exclusion criteria
* Pregnant or lactating women, and women of childbearing age who have not taken adequate contraceptive measures; * Patients with a history of other malignant tumors within 5 years, except for those with a history of cured cervical carcinoma in situ or non-melanoma skin cancer; * Patients with the following severe or uncontrolled diseases: severe heart disease, unstable condition despite treatment, myocardial infarction, congestive heart failure, unstable angina pectoris, significant pericardial effusion or unstable arrhythmia within 6 months before enrollment; definite neurological or psychiatric disorders, including dementia or epileptic seizures; severe or uncontrolled infections; active disseminated intravascular coagulation, or patients with obvious bleeding tendencies; * Participants who received live vaccines (including live attenuated vaccines) within 28 days before first dose. * Presence of any active autoimmune disease or history of autoimmune disease. * History of allogeneic haematopoietic stem-cell or solid-organ transplantation. * Hypertension uncontrolled by medication before enrollment, defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg. * Other conditions where the investigator deems the patient unsuitable for participation in this trial;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PFS | From date of enrollment until the end of treatment or the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 24 months | Progression-free survival |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR | The proportion of subjects achieving complete response (CR) or partial response (PR) among all enrolled subjects; assessed per RECIST 1.1 every 6 weeks until disease progression or death, assessed up to approximately 12 months | Objective response rate |
| DCR | The proportion of subjects achieving CR, PR, or stable disease (SD) among all enrolled subjects; assessed per RECIST 1.1 every 6 weeks until disease progression or death, assessed up to approximately 12 weeks | disease control rate |
| OS | From date of enrollment until the date of death from any cause, assessed up to approximately 36 months | overall survival |
Countries
China
Contacts
CONTACTXiaodong Zhu
Outcome results
None listed