Clinical trial NCT03048474 (phase 2, status: completed)
Conditions: malignant pleural mesothelioma
ICD codes: C45.9, C45.0, C45.1, C45.2, C45.7
Drugs: nivolumab and ipilimumab
SMILES: [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1
Eligibility criteria:

        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

        Exclusion Criteria:

          -  Medical or psychological impediment to comply with the protocol

          -  Patients with only peritoneal MPM

          -  Prior malignancy except adequately treated basal cell or squamous cell skin cancer,
             superficial or in-situ cancer of the bladder or other cancer for which the patient has
             been disease-free for at least five years

          -  Concomitant participation in another clinical trial (by the investigator's judgment)

          -  Uncontrolled pleural/peritoneal effusion, pericardial effusion or ascites requiring
             recurrent drainage procedures (once monthly or more frequently)

          -  Uncontrolled tumor-related pain Patients requiring pain medication must be on a stable
             regimen at study entry. Symptomatic lesions amenable to palliative radiotherapy should
             be treated prior to enrolment.

          -  Previous treatment with any checkpoint inhibitor

          -  Pregnant or lactating women

          -  Patients with brain metastases

          -  History of or active autoimmune disease (e.g. pneumonitis; rheumatoid arthritis;
             severe form of psoriasis; uncontrolled type I diabetes or hypothyroidism)

          -  History of idiopathic pulmonary fibrosis (including pneumonitis) or unresolved
             drug-induced pneumonitis, organizing pneumonia, or active pneumonitis on screening
             chest CT scan

          -  History of relevant gastrointestinal disease, including, but not limited to, Crohn's
             disease, ulcerative colitis, recurrent diverticulitis

          -  Prior allogenic bone marrow transplantation or prior solid organ transplantation

          -  History of HIV

          -  Patients with history of HBV infection are eligible if serological profile is
             compatible with past/resolved infection (defined as negative HBsAg test and positive
             antibody to HBV core antigen [anti-HBc] antibody test) and HBsAg test and HBV-DNA are
             both negative prior to Cycle 1, Day 1

          -  Patients with history of HCV infection must be screened for HCV-RNA PCR test prior to
             Cycle 1, Day 1, and are eligible if the test turns negative

          -  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