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Purpose/Objective(s): • Platinum-based chemotherapy with pemetrexed is an appropriate first line treatment option for unresectable malignant pleural mesothelioma (MPM) • The DREAM¹ and PrE0505² Phase II trials combined durvalumab (PD-L1 inhibitor) with a platinum and pemetrexed both exceeding pre-specified response with acceptable toxicity • CheckMate 7433 recently reported an overall survival benefit with ipilimumab plus nivolumab vs. chemotherapy (HR 0.74, 95% CI 0.50 to 0.91). However, this benefit was less apparent in the 75% of patients with epithelioid histology (HR 0.86, 95% CI 0.69 to 1.08) • Clinical trials to further explore optimal first line treatment for MPM with immunotherapy are needed Materials/Methods International, open label, randomised (2:1), multi-centre, phase 3 trial • 480 patients (320 durvalumab and chemotherapy, 160 chemotherapy) to be recruited over 27 months and followed for another 24 months • This provides over 85% power if the true hazard ratio for overall survival is 0.70 with 2-sided alpha of 0.05, assuming a median survival of 15 months in the chemotherapy group, 21.4 months in the durvalumab and chemotherapy group, with an allowance for crossover Results TBD Conclusion TBD

Background: Durvalumab monotherapy has demonstrated promising objective tumour response (OTR) and safety in advanced endometrial cancer with deficient MMR. We report here updated OTR, progression-free survival (PFS) and overall survival (OS) results based on central pathology MMR review from the PHAEDRA trial. Method(s): Participants (pts) had MMR-proficient (pMMR)or -deficient (dMMR) AEC progressing after 0-3 lines of chemotherapy and were treated with durvalumab 1500mg IV Q4W. The primary endpoint was OTR (complete response [CR] or partial response [PR] byiRECIST). Secondary endpoints included PFS, OS, OTRby RECIST 1.1, adverse events, quality of life, and tertiary translational objectives to determine associations between molecular biomarkers and OTR. Result(s): 71 pts with AEC were recruited from Feb 2017toSep 2018: 36 dMMR and 35 pMMR based oncentral MMR review. Median follow-up forOS were16 vs 21 months in dMMR vspMMR pts. Median age: 67 (range 36-81); ECOG PS: 0-1in 96%, and 2in 4%. Pathology: endometrioid in 94% and 57%; serous in 0%and 31%; grade3 (most recent histology): 41% and 85% (dMMR and pMMR respectively). Durvalumab was the 1st, 2nd and subsequent line of non-hormonal therapy in 58%, 39%, and 3% pts with dMMR and 9%, 63%, and 29% pts with pMMR. Among dMMR pts, the OTR rate was 47% (17/36, 95% CI 32-63%): 6 CR,11 PRand 6stable disease (SD).OTR rate was 57% as 1st line and 38%as 2nd line. Among pMMR pts, the OTR rate was 3%(1/35, 95% CI 1-15%):1 PR and 10SD. Median PFS was 5.5 vs1.8 monthsin dMMR vs pMMR pts. 12-month OSwas 71% vs51% in dMMR vs pMMR, with median OS not reached for dMMR vs11.5 months for pMMR participants. Conclusion(s): Durvalumab monotherapy showed promising activity and safety in AEC with dMMR regardless of prior lines of chemotherapy, but there was limited evidence of activity inAEC with pMMR.