Australia has the second highest incidence and death rate from malignant pleural mesothelioma (MPM) worldwide, after the United Kingdom. DREAM is an open-label, single arm, multi-centre, phase II trial designed to determine the activity, safety and tolerability of durvalumab combined with first-line chemotherapy in MPM. ACTRN12616001170415. Key eligibility criteria included all histological subtypes of MPM planned for first-line cisplatin and pemetrexed, unsuitability for radical surgery, no prior radiotherapy to measurement sites, and ECOG performance status of 0-1. Response was assessed using the mRECIST (modified Response Evaluation Criteria in Solid Tumors for MPM). Patients received durvalumab (1125mg), cisplatin (75mg/m2) and pemetrexed (500mg/m2) 3-weekly for a maximum of 6 cycles, followed by durvalumab alone (1125 mg 3-weekly) up to 12 months or until progression or unacceptable toxicity. The primary endpoint was progression-free survival at 6 months (PFS6). Between Dec 2016 and Sep 2017, 54 patients were recruited. The median age was 68 (42-82) with 82% male and 60% ECOG 0. Forty-five patients (82%) had epithelioid subtype MPM. 31/54 (57%) of patients met primary endpoint of PFS6 with a median PFS of 6.8 months (95% CI: 5.4-9.0), at a median follow up time of 12 months, successfully rejecting the null hypothesis. The objective response rate (ORR) was 48% using mRECIST and 50% using iRECIST. The median duration of response was 6.5 months. 36 patients experienced grade 3-5 adverse events. Of four deaths on study, none were considered related to durvalumab treatment. Seventeen patients had irAEs of any grade, including 8 with G3-5 irAEs. Overall survival is maturing and will be presented at the meeting. Combination durvalumab with first-line chemotherapy for unresectable MPM showed promising activity and acceptable tolerability, with expected immune toxicities. Further evaluation to compare with chemotherapy alone will be generated through a phase 3 randomised controlled trial.