DREAM: A phase II study of durvalumab with first line chemotherapy in mesothelioma-First results

Background: DREAM is an open-label, single arm, multi-centre, phase II trial with a safety run in designed to determine the activity, safety and tolerability of durvalumab combined with cisplatin and pemetrexed as first line therapy in malignant pleural mesothelioma (MPM). ANZ Clinical trial registry number: ACTRN12616001170415. Methods: Chemotherapy-naïve patients with MPM of all histological subtypes, planned for first-line cisplatin and pemetrexed who had not received prior radiotherapy and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 were eligible. 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) until progression or to 12 months total therapy. Primary endpoint was progression-free survival at 6 months (PFS6). The design provides >90% power if the true PFS6 rate is 65%, with 5% type I error using an expected PFS6 from standard treatment of 45%. Matching tissue and bloods were collected for translational research. Results: Between Dec 2016 to Sep 2017 54 participants were recruited. The median age was 68 (42-82) with 82% male and 60% ECOG 0. They received a median of 6 cycles of chemotherapy (range 1-6) and 7 of durvalumab (given with and without chemotherapy) (range 1-18). The 6-patient safety run in confirmed the tolerability of chemoimmunotherapy. In the first 31 evaluable patients (pre-specified primary interim analysis), PFS6 based on modified RECIST (mRECIST) for MPM was 71%. The objective response rate (ORR) was 61% using mRECIST and 53% using iRECIST. Thirty-one patients (57%) experienced adverse events (AEs) that were grade ≥3. Nineteen patients (35%) had immune-related (ir) AEs including 2 grade 3 irAEs. Conclusions: In MPM, adding durvalumab to first line treatment with cisplatin and pemetrexed had higher rates of PFS6 and ORR than expected for chemotherapy alone, with acceptable tolerability. The final result of PFS6 for all 54 patients will be reported in late 2018