Pembrolizumab and Hypofractionated Stereotactic Radiotherapy in Patients With Malignant Pleural Mesothelioma

Inclusion Criteria: 1. Patients should be ≥18 years old on the day of signing the informed consent. 2. Patients must have a histological or cytological diagnosis of MPM. 3. Patients should have non-radically treatable MPM (i.e. not being considered for extrapleural pneumonectomy or pleurectomy and decortication). 4. Patients must have measurable disease as assessed by mRECIST (i.e. at least a 1 cm rind of MPM at 2 sites on 3 different levels). 5. Patients must have had disease progression or be intolerant of standard first-line palliative chemotherapy for MPM. Patients who have declined first-line palliative chemotherapy must have been suitable for platinum-doublet combination chemotherapy. 6. Patient should have an ECOG performance status 0-1. 7. Patients should be able to tolerate a course of stereotactic radiotherapy as assessed by the investigator. 8. Patients should have pleural based disease, away from critical structures, and suitable for treatment to part of lesion with SBRT for pleural mesothelioma. 9. Patients must have adequate organ function including MRC dyspnoea score \<3 and adequate baseline lung function tests, with an FEV1 \> 0.8L or \>30% of predicted and a TLCO \> 30%. 10. Demonstrate adequate organ function (based on bloods within 10 days of C1D1). 11. Have provided tissue from an archival tissue sample or newly obtained tissue sample. 12. Female patient of childbearing potential should have a negative serum pregnancy within 72 hours prior to receiving the first dose of study medication (C1D1). Female patients of childbearing potential should be willing to use highly effective methods of contraception for the course of the study through 120 days after the last dose of study medication. Female of childbearing potential is defined as women following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. 13. Male patients should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. 14. Be willing to provide informed consent for the trial. Exclusion criteria 1. Patients who have taken any investigational medicinal product or have used an investigational device within 4 weeks of the first dose of pembrolizumab. Patients are allowed to participate in additional observational studies. 2. Patients who have received prior chemotherapy, targeted small molecule therapy or radiotherapy within 4 weeks prior to the first dose of pembrolizumab. 3. Patients with a diagnosis of immunodeficiency or be receiving systemic steroid therapy (\>7.5 mg of prednisone / \>1 mg of dexamethasone or their equivalent dose) or any other form of immunosuppressive therapy within 7 days prior to the first dose. 4. Patients with evidence of active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents or an autoimmune disease that is currently quiescent off any treatment, but deemed at risk of a significant flare if treated on this protocol. 5. Patients who have received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). 6. Patients with evidence of active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided the brain metastases are stable and there is no evidence of new or enlarging brain metastases. 7. Patients who have had previous radiotherapy to the thorax or other neighbouring region that would preclude the safe administration of SBRT for MPM. 8. Patients with evidence of interstitial lung disease or active, non-infectious pneumonitis. 9. Patients with evidence of additional malignancy that is progressing or requires active treatment. 10. Patients with a history or current evidence of any condition, therapy, or laboratory abnormality that might confound trial results, interfere with the patient's participation or is not in the best interest of the patient. 11. Patients with psychiatric or substance abuse disorders that would interfere with patients participation. 12. Patients who are pregnant / breastfeeding or expecting to conceive within the duration of the trial, starting with the screening visit through 120 days after the last dose. 13. Patients with a history of HIV, HIV 1/2 antibodies, Hepatitis B or Hepatitis C. 14. Patients with any active infection requiring systemic treatment 15. Patients who have received a live vaccine within 30 days prior to the first dose of trial treatment. 16. Patients with known hypersensitivity to the active substance pembrolizumab or to any of the excipients listed in the IB.