Abstract CT094: Durvalumab (D) vs placebo (P) after concurrent chemoradiotherapy (cCRT) in limited-stage small-cell lung cancer (LS-SCLC): Outcomes by PD-L1 expression in ADRIATIC

Abstract Background: At the first planned interim analysis of the phase 3 ADRIATIC study (NCT03703297), consolidation D significantly improved the dual primary endpoints of overall survival (OS; HR 0.73; 95% CI 0.57-0.93; p=0.0104) and progression-free survival (PFS; HR 0.76; 95% CI 0.61-0.95; p=0.0161) vs P in patients (pts) with LS-SCLC with no progression after cCRT. Although PD-L1 is not currently a validated immunotherapy biomarker in SCLC (unlike NSCLC) and is generally expressed at low levels in this setting, PD-L1 was evaluated as a potential biomarker in ADRIATIC. Methods: Pts with stage I-III LS-SCLC (stage I/II inoperable), WHO performance status 0/1, and no progression after cCRT, were randomized 1-42 days post cCRT to D (n=264), D + tremelimumab (n=200; arm remains blinded), or P (n=266). The VENTANA PD-L1 (SP263) immunohistochemistry assay was used for central retrospective testing of pre-cCRT tissue samples. OS and PFS were assessed in the PD-L1-evaluable population and in subgroups with PD-L1 expression ≥1% on tumor cells (TC) and/or immune cells (IC) (secondary endpoint) and <1% on TC and IC (data cutoff: Jan 15, 2024). Results: Among 162 (61.4%) and 171 (64.3%) pts in the D and P arms who were evaluable for PD-L1, improvements in OS (HR [D vs P] 0.73 [95% CI 0.53-0.99]) and PFS (HR 0.80 [0.60-1.06]) were of similar magnitude to those in the ITT population. Of the PD-L1-evaluable pts, 51.9% (84/162) in the D arm and 57.3% (98/171) in the P arm had PD-L1 TC or IC ≥1%. D appeared to improve OS and PFS vs P in subgroups with TC or IC ≥1% and with TC and IC <1% (Table), consistent with the ITT population. Conclusions: Among the PD-L1-evaluable population in ADRIATIC, 54.7% (182/333) of pts had PD-L1 TC or IC ≥1%. Consolidation D appeared to improve OS and PFS vs P irrespective of PD-L1 expression based on a cutoff of 1% on TC and/or IC, further supporting consolidation D as the new standard of care in pts with LS-SCLC with no progression after cCRT. Citation Format: Christine Hann, Ying Cheng, David Spigel, Byoung Chul Cho, Jian Fang, Yuanbin Chen, Yoshitaka Zenke, Qiming Wang, Reyes Bernabe, John Wen-Cheng Chang, Sema Sezgin Goksu, Lin Wu, Gyeong-Won Lee, Michael Thomas, Yuichiro Ohe, Frank Griesinger, Leah Szadkowski, Hema Gowda, Yashaswi Shrestha, Suresh Senan. Durvalumab (D) vs placebo (P) after concurrent chemoradiotherapy (cCRT) in limited-stage small-cell lung cancer (LS-SCLC): Outcomes by PD-L1 expression in ADRIATIC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT094.