Cho, Byoung ChulByoung ChulChoAhn, Myung-JuMyung-JuAhnNishio, MakotoMakotoNishioMurakami, HaruyasuHaruyasuMurakamiWan-Kim, DongDongWan-KimKim, Sang-WeSang-WeKimKaram, Sana DSana DKaramEstival, AnaAnaEstivalCHIA-CHI LINTrigo, Jose ManuelJose ManuelTrigoAlvarez, RosaRosaAlvarezWang, Chih LiangChih LiangWangXie, MingchaoMingchaoXieIyer, SoniaSoniaIyerArmstrong, JonJonArmstrongChugh, PritiPritiChughJiang, HaiyiHaiyiJiangBauman, Julie EJulie EBauman2026-01-292026-01-292025-10https://scholars.lib.ntu.edu.tw/handle/123456789/735662The phase 1 CLOVER study (NCT03509012) evaluated durvalumab with or without tremelimumab in combination with concurrent chemoradiotherapy (cCRT) in patients with advanced solid tumors; here, we report findings from the limited-stage SCLC (LS-SCLC) cohort. Patients with pathologically confirmed LS-SCLC whose disease could be encompassed within a radical radiation portal received durvalumab (arms 1 and 2) or durvalumab plus tremelimumab (arms 3 and 4) in combination with cCRT (cisplatin-etoposide and either standard radiotherapy [arms 1 and 3] or hyperfractionated radiotherapy [arms 2 and 4]). The primary end point was safety and tolerability. Preliminary efficacy and candidate biomarkers of response were assessed. Overall, 33 patients were enrolled: 12 in arm 1, 12 in arm 2, six in arm 3, and three in arm 4. No patients had dose-limiting toxicity. Grade 3 or 4 adverse events occurred in 79.2% of patients from arms 1 and 2 and 88.9% from arms 3 and 4; the most common were hematologic events. In arms 1, 2, 3, and 4, objective response rate was 66.7%, 66.7%, 83.3%, and 100.0%, disease control rate was 90.9%, 100.0%, 100.0%, and 100.0% at 18 weeks and 72.7%, 83.3%, 100.0%, and 100.0% at 48 weeks, and the median progression-free survival (PFS) (95% confidence interval) was 9.2 months (5.3‒not estimable [NE]), 16.6 months (8.4-NE), not reached (16.6-NE), and 9.3 months (6.3-NE), respectively. In exploratory biomarker analyses, no difference in PFS by programmed cell death-ligand 1 expression level was observed; median PFS was numerically greater in high versus low tumor inflammation signature and expression subgroups. Durvalumab in combination with cCRT, with or without tremelimumab, was tolerable and active in patients with LS-SCLC.enCLOVERChemoradiotherapyDurvalumabLimited-stage SCLCTremelimumab[SDGs]SDG2journal article10.1016/j.jtocrr.2025.10088441069379