A Randomised Phase II Open-label Study With a Phase Ib Safety lead-in Cohort of ONCOS-102, an Immune-priming GM-CSF Coding Oncolytic Adenovirus, and Pemetrexed/Cisplatin in Patients With Unresectable Malignant Pleural Mesothelioma

Inclusion Criteria: * Written informed consent. * Male or female, ≥18 years of age. * Histologically confirmed unresectable (advanced) malignant pleural mesothelioma in patients who are not candidates for curative surgery and for whom therapy with pemetrexed in combination with cisplatin or carboplatin is considered appropriate. This include: * patients who are naïve to chemotherapy, * and those who have already received pemetrexed in combination with cisplatin or carboplatin to which their tumour initially responded, but they have relapsed after at least 6 months. The patient may be evaluated by a multidisciplinary consultation (according to hospital procedure), however the final decision about the inclusion of a patient is made by the principal investigator. * Measurable disease according to Response Evaluation in Solid Tumour (RECIST 1.1). * Tumour must be accessible to intratumoural (i.t.) injections and to tumour core needle biopsy or thoracoscopy for tissue sampling and immunohistochemistry analysis. * The patients must be eligible to receive the study specific chemotherapies, including cyclophosphamide, according to the SPCs and local practice. * Eastern Cooperative Oncology Group (ECOG)/World Health Organization (WHO) performance score 0 to 1. * Acceptable liver, renal, and haematological functions. * All women of childbearing potential must have a negative urine or serum pregnancy test at screening and all patients must agree to use barrier contraception (i.e. condom) during study treatment and for 2 months after the last virus treatment, 6 months after the last dose of pemetrexed/cisplatin/carboplatin and 12 months after the dose of cyclophosphamide. Exclusion Criteria: * Receipt of oncolytic virus treatment, or vaccination with a vaccine containing live virus within 4 weeks before Day 1. * Use of significant immunosuppressive medication, including high dose corticosteroid (defined as the equivalent of \>10 mg/day prednisone) within 4 weeks before Day 1. * Patients who participated in a study with an investigational drug or device within 4 weeks prior to Day 1. * Active bacterial, viral, or fungal infections, requiring systemic therapy. * Severe arrhythmia, heart failure, previous cardiac infarction, or acute inflammatory heart disease. * Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the patient, if included in this study. * Known infection with HIV, hepatitis B, or hepatitis C. * Known brain metastases. * History of organ transplant. * Females who are pregnant or breast feeding. * Unwillingness or inability to comply with the study protocol for any reason. * Patients with pre-existing hearing loss or neuropathy that may worsen due to potential neurotoxicity from cisplatin. * Patients with a history of hypersensitivity to cisplatin or carboplatin or pemetrexed or cyclophosphamide (or any of its metabolites). * Patients who are taking phenytoin for prophylactic use. * History of malignant tumour, unless the patient has been without evidence of disease for at least 3 years, or the tumour was a non-melanoma skin tumour, cervical carcinoma in situ, or prostatic carcinoma in situ.