A single arm phase II study of Nivolumab in patients with progressive malignant pleural mesothelioma: interim biopsy analysis to determine efficacy. Acronym: NivoMes Study

* Patients with proven malignant pleural mesothelioma, who have progressive disease after chemotherapy in first or second line.
* Patients with histological or cytological diagnosed malignant pleural mesothelioma and age > 18 years.
* Progressive disease after at least one course of chemotherapy.
* Previous chemotherapy or experimental therapy * 4 weeks ago
* Medically suitable for limited surgical intervention (pleural biopsies up to limited pleurectomy).
* Not considered candidates for trimodality treatment (as part of a study).
* Measurable or evaluable disease (see tumor response assessment).
* Ability to understand the study and give signed informed consent prior to beginning of protocol specific procedures including the approval of a second thoracoscopy or transthoracic pleural biopsy after the third course.
* Radiotherapy is allowed when this is given for palliation of painful sites, the interval is > 12 weeks and not all tumor is within the irradiation field.
* WHO performance status 0 or 1 (see appendix 1).
* Adequate organ function as evidenced by the following peripheral blood counts or serum chemistries at study entry:
* Hematology: Neutrophil count * 1.5 x 109/l, Platelets * 150 x 109/l, Hemoglobin * 6,0 mmol/l.
* Chemistry: Total serum bilirubin * 1.5 times within the upper limits of normal (ULN); ASAT and ALAT * 2.5 x ULN, AP (alkaline phosphatases) < 5x ULN (unless bone metastases are present in the absence of any liver disease).
* Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception to avoid pregnancy during treatment and for 23 weeks after the last dose of investigational drug.
* Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the first startdose of nivolumab.
* Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year during treatment and for a period of 31 weeks after the last dose of investigational drug.
* Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile) as well as azoospermic men do not require contraception.

* Active uncontrolled infection, severe cardiac dysfunction or uncorrectable bleeding tendency.
* Inability to perform biopsies of the pleural lesions.
* Symptomatic peripheral neuropathy * grade 2 according to NCI CTC, version 4.0.
* Presence of symptomatic CNS metastases.
* Unstable peptic ulcer, unstable diabetes mellitus or other serious disabling condition.
* Impaired renal function: creatinine clearance less than 50ml/min.
* Concomitant administration to any other experimental drugs under investigation.
* Patients are excluded if they have an active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
* Patients are excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immuno-suppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses < 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
* Patients are excluded if they have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.