TY - JOUR T1 - Clinical activity of durvalumab for patients with advanced mismatch repair-deficient and repair-proficient endometrial cancer. A nonrandomized phase 2 clinical trial JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1136/jitc-2020-002255 VL - 9 IS - 6 SP - e002255 AU - Yoland Antill AU - Peey-Sei Kok AU - Kristy Robledo AU - Sonia Yip AU - Michelle Cummins AU - Deborah Smith AU - Amanda Spurdle AU - Elizabeth Barnes AU - Yeh Chen Lee AU - Michael Friedlander AU - Sally Baron-Hay AU - Catherine Shannon AU - Jermaine Coward AU - Philip Beale AU - Geraldine Goss AU - Tarek Meniawy AU - Janine Lombard AU - John Andrews AU - Martin R Stockler AU - Linda Mileshkin A2 - , Y1 - 2021/06/01 UR - http://jitc.bmj.com/content/9/6/e002255.abstract N2 - Background In this study, we assessed the activity of durvalumab, an antibody to programmed death ligand-1, in two cohorts of women with advanced endometrial cancers (AEC)—mismatch repair proficient (pMMR) and mismatch repair deficient (dMMR).Methods A multicenter phase two study was performed in women with AEC with pMMR tumor progressing after one to three lines of chemotherapy and women with AEC with dMMR tumor progressing after zero to three lines of chemotherapy. Mismatch repair status was based on immunohistochemistry expression. All women received durvalumab 1500 mg given every 4 weeks until progression or unacceptable toxicity. The primary endpoint was objective tumor response by RECIST V.1.1 modified for immune-based therapeutics.Results Seventy-one women were recruited: 35 dMMR and 36 pMMR. Median follow-up was 19 vs 21 months in dMMR versus pMMR, respectively. Median age was 67 years. Histology in dMMR versus pMMR included endometrioid (94% vs 57%) and serous (0% vs 31%) and was high grade in 26% vs 74%. The objective tumor response rate (OTRR) in the dMMR cohort was 47% (17/36, 95% CI 32 to 63), including 6 complete responses and 11 partial responses (PRs)) vs 3% in the pMMR cohort (1/35, 95% CI 1 to 15, PR). In the dMMR cohort, durvalumab was the first-line therapy in 58% (OTRR 57%) and the second-line therapy in 39% (OTRR 38%). Median progression-free survival was 8.3 months in the dMMR cohort vs 1.8 months in the pMMR cohort. The 12-month overall survival (OS) rate was 71% in dMMR vs 51% in pMMR, with median OS not reached for dMMR vs 12 months for pMMR. Immune-related adverse events occurred in 14 women, mostly grades 1–2.Conclusion Durvalumab monotherapy showed promising activity and acceptable safety in AEC with dMMR regardless of prior lines of chemotherapy, but activity was limited in AEC with pMMR.Trial registration numbers ANZGOG1601, ACTRN12617000106336, and NCT03015129.Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplemental information. Individual deidentified subject data that underlie the results reported in this article will be shared upon reasonable request. Study protocol has been shared. Additional related documents will be available (eg, s statistical analysis plan) upon reasonable request. ER -