Abstract LB105: Translational analyses from the randomized phase 3 DREAM3R trial: DuRvalumab with chEmotherapy as first line treAtment in advanced pleural Mesothelioma

作者：Valsamo Anagnostou, Anna K. Nowak, Chris Brown, Brett G. Hughes, Noushin Niknafs, Tracy Hoang, Jaime Wehr, Connull Leslie, Qiong Meng, Asimina Zoitou, Kennet J. O’Byrne, Wee L. Chin, Thomas John, Peter Illei, Sonia Yip, Nick Pavlakis, Julie Brahmer, Martin R. Stockler, Patrick M. Forde, A. J. Cook · 发表于：Cancer Research · 年份：2026 · DOI：10.1158/1538-7445.am2026-lb105 · 研究领域：Occupational and environmental lung diseases、Cancer Immunotherapy and Biomarkers、Myasthenia Gravis and Thymoma

Abstract Introduction: The phase 3 randomized DREAM3R clinical trial evaluated durvalumab + chemotherapy (D+Ch) compared to chemotherapy alone (Ch) for patients with pleural mesothelioma (PM) and showed an improvement in overall response rate (ORR) with D+Ch (Clinical trial identifier: NCT04334759). The study enrolment was terminated early due to slow accrual, and the primary endpoint of overall survival (OS) was not met. Here, we report translational analyses of genomic landscapes and PD-L1 expression and their association with clinical endpoints in the DREAM3R trial. Methods: Between February 2021 and November 2023, 173 participants with unresectable PM were randomized to D+Ch (n=113) vs Ch (n=60); most (94%) had epithelioid PM. Overall survival (OS) was the primary endpoint; secondary endpoints included progression-free survival (PFS) and objective response rate (ORR; by modified RECIST for PM). Pre-treatment tumor PD-L1 expression was evaluated by immunohistochemistry (pharmDx 22C3) in participants with available tissue. Tumor-positive score (TPS) was recorded, and PD-L1+ vs PD-L1- cohorts (≥1% vs <1%) were compared for OS, PFS, and ORR. Tumor mutational burden (TMB) estimates were derived by counting sequence alterations in coding regions using whole exome sequencing (n=91 in the D+Ch and n=35 in the Ch arm). Mutations were characterized by recurrence and functional consequence, and enrichment analyses were performed for individual mutations and for mutations that...