Ipilimumab and Nivolumab in the Treatment of Malignant Pleural Mesothelioma

Inclusion Criteria

• •Signed informed consent form
• •Age ≥ 18 years
• •WHO-ECOG performance status 0 or 1
• •Able to comply with the study protocol, in the investigator's judgment
• •Patients with histologically confirmed diagnosis of the recurrence of MPM. Any pleural MPM subtype is permitted for inclusion in the study
• •Progressive disease after at least one prior systemic treatment with a platinum-based doublet (both cisplatin and carboplatin are allowed) for unresectable MPM. All prior cytotoxic toxicities must have resolved to grade ≤ 1 prior to registration
• •Measurable disease on CT scan, according to modified RECIST Criteria for Mesothelioma (Byrne MJ, 2004)
• •Life expectancy ≥ 12 weeks
• •Adequate hematologic and organ function, defined by the following laboratory results, obtained within 14 days prior to the first study treatment:
• •* Absolute neutrophil count (ANC) ≥ 1500 cells/µL (without granulocyte colony-stimulating factor support within 2 weeks prior to Cycle 1, Day 1)
• •* WBC count ≥ 3000 cells/µL
• •* Lymphocyte count ≥ 250 cells/µL
• •* Platelet count ≥ 100.000/µL (without transfusion within 2 weeks prior to Cycle 1, Day 1)
• •* Hemoglobin ≥ 5.6 mmol/L
• •* Serum albumin ≥ 25 gr/L
• •* AST, ALT and alkaline phosphatase ≤ 2.5 x ULN, with the following exceptions: patients with documented liver or bone metastases: alkaline phosphatase ≤ 5 x ULN
• •* Serum bilirubin ≤ 1.5 x ULN Patients with known Gilbert disease who have serum bilirubin level ≤ 3 x ULN may be enrolled
• •* INR and aPTT ≤ 1.5 x ULN Patients receiving therapeutic anticoagulation should be on a stable dose Creatinine clearance ≥ 45 mL/min Cockcroft-Gault, Chronic Kidney Disease Epidemiology Collaboration or Modification of Diet in Renal Disease formulae may be used; 24-hour urine collection is not required
• •Women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus) and men with partners of childbearing potential, must agree to use adequate contraception (double barrier birth control) for the whole duration of study treatment and for 3 months after the last dose of therapy
• •Women of childbearing potential must have a negative serum or urine pregnancy test within 48 hours prior the first dose of treatment
• •Other serious concomitant disease, including:
• •Active tuberculosis Severe infections within 4 weeks prior to Cycle 1, Day 1 Significant cardiovascular disease (NYHA class III or IV), myocardial infarction within the previous 6 months, unstable angina, or unstable arrhythmias Significant pulmonary (asthma or COPD) or hepatic disease or other illness considered by the investigator to constitute an unwarranted high risk for investigational treatment
• •Major surgical procedures within 28 days prior to Cycle 1, Day 1
• •Concurrent medications Treatment with systemic immunosuppressive medications, including but not limited to prednisone (with specific exceptions; see below), cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[anti-TNF\] agents) within 2 weeks prior to Cycle 1, Day 1.
• •The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) is allowed.
• •The use of systemic prednisone at the dosage of 10 mg/day or lower (or equivalent) is allowed.
• •Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1