Durvalumab With or Without Tremelimumab in Combination With Chemoradiotherapy in Patients With Limited-Stage SCLC: Results from the Phase 1 CLOVER Study.
Journal
JTO clinical and research reports
Journal Volume
6
Journal Issue
10
ISSN
2666-3643
Date Issued
2025-10
Author(s)
Cho, Byoung Chul
Ahn, Myung-Ju
Nishio, Makoto
Murakami, Haruyasu
Wan-Kim, Dong
Kim, Sang-We
Karam, Sana D
Estival, Ana
Trigo, Jose Manuel
Alvarez, Rosa
Wang, Chih Liang
Xie, Mingchao
Iyer, Sonia
Armstrong, Jon
Chugh, Priti
Jiang, Haiyi
Bauman, Julie E
Abstract
The 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.
Subjects
CLOVER
Chemoradiotherapy
Durvalumab
Limited-stage SCLC
Tremelimumab
SDGs
Type
journal article