Durvalumab联合或不联合Tremelimumab联合放化疗治疗有限期SCLC患者：来自1期CLOVER研究的结果

IF 3.5 Q2 ONCOLOGY

JTO Clinical and Research Reports Pub Date : 2025-08-05 DOI:10.1016/j.jtocrr.2025.100884

Byoung Chul Cho MD, PhD , Myung-Ju Ahn MD , Makoto Nishio MD , Haruyasu Murakami MD , Dong Wan-Kim MD , Sang-We Kim MD , Sana D. Karam MD , Ana Estival PhD , Chia-Chi Lin MD, PhD , Jose Manuel Trigo MD , Rosa Alvarez MD , Chih Liang Wang MD , Mingchao Xie PhD , Sonia Iyer PhD , Jon Armstrong MSc , Priti Chugh PhD , Haiyi Jiang MD , Julie E. Bauman MD

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引用次数: 0

摘要

1期CLOVER研究（NCT03509012）评估了durvalumab联合或不联合tremelimumab联合同步放化疗（cCRT）治疗晚期实体瘤患者；在这里，我们报告了来自有限期SCLC （LS-SCLC）队列的研究结果。方法病理证实的LS-SCLC患者接受durvalumab（第1组和第2组）或durvalumab + tremelimumab（第3组和第4组）联合cCRT（顺铂- etopo苷加标准放疗[第1组和第3组]或超分割放疗[第2组和第4组]）治疗。主要终点是安全性和耐受性。评估初步疗效和候选生物标志物。结果共纳入33例患者：1组12例，2组12例，3组6例，4组3例。没有患者出现剂量限制性毒性。3级或4级不良事件发生在第1组和第2组的79.2%和第3组和第4组的88.9%；最常见的是血液学事件。在1、2、3和4组中，客观缓解率分别为66.7%、66.7%、83.3%和100.0%，18周时疾病控制率分别为90.9%、100.0%、100.0%和100.0%，48周时疾病控制率分别为72.7%、83.3%、100.0%和100.0%，中位无进展生存期（PFS）（95%置信区间）分别为9.2个月（5.3 -不可估计[NE]）、16.6个月（8.4-NE）、未达到（16.6 - NE）和9.3个月（6.3-NE）。在探索性生物标志物分析中，程序性细胞死亡配体1表达水平与PFS无差异；肿瘤炎症特征和CD8A表达高亚组与低亚组的中位PFS数值更高。结论durvalumab联合cCRT，无论是否联合tremelimumab，在LS-SCLC患者中是可耐受的和有效的。

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Durvalumab With or Without Tremelimumab in Combination With Chemoradiotherapy in Patients With Limited-Stage SCLC: Results from the Phase 1 CLOVER Study

Introduction

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.

Methods

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.

Results

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 CD8A expression subgroups.