简要报告：在预先接受程序性死亡受体-配体 1 单药治疗的晚期 NSCLC 患者中，度伐利尤单抗联合替西木单抗的安全性和抗肿瘤活性：来自 1b 期临床试验的结果。
Brief Report: Safety and Antitumor Activity of Durvalumab Plus Tremelimumab in Programmed Cell Death-(Ligand)1-Monotherapy Pretreated, Advanced NSCLC: Results From a Phase 1b Clinical Trial.
机构信息
Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.
Co-Director, Virginia Cancer Specialists Research Institute and NEXT Oncology, Fairfax, Virginia.
出版信息
J Thorac Oncol. 2023 Aug;18(8):1094-1102. doi: 10.1016/j.jtho.2023.04.020. Epub 2023 May 4.
INTRODUCTION
Although first-line immunotherapy approaches are standard, in patients with non-small cell lung cancer (NSCLC) previously treated with programmed cell death protein-1 or programmed death-(ligand)1 (PD-[L]1) inhibitors, the activity of combined CTLA-4 plus PD-(L)1 inhibition is unknown. This phase 1b study evaluated the safety and efficacy of durvalumab plus tremelimumab in adults with advanced NSCLC who received anti-PD-(L)1 monotherapy as their most recent line of therapy.
METHODS
Patients with PD-(L)1-relapsed or refractory NSCLC were enrolled between October 25, 2013, and September 17, 2019. Durvalumab 20 mg/kg plus tremelimumab 1 mg/kg was administered intravenously every 4 weeks for four doses, followed by up to nine doses of durvalumab monotherapy every 4 weeks for up to 12 months of treatment or disease progression. Primary end points included safety and objective response rate (ORR) on the basis of Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) per blinded independent central review; secondary end points were ORR on the basis of RECIST v1.1 per investigator; duration of response, disease control, and progression-free survival on the basis of RECIST v1.1 per blinded independent central review and investigator; and overall survival.
CLINICALTRIALS
gov identifier: NCT02000947.
RESULTS
PD-(L)1-refractory (n = 38) and PD-(L)1-relapsed (n = 40) patients were treated. The most common treatment-related adverse events were fatigue (26.3%, PD-(L)1-refractory patients) and diarrhea (27.5%, PD-(L)1-relapsed patients). Grade 3 to 4 treatment-related adverse events occurred in 22 patients. Median follow-up duration was 43.6 months for PD-(L)1-refractory patients and 41.2 months for PD-(L)1-relapsed patients. The ORR was 5.3% for PD-(L)1-refractory patients (one complete response, one partial response) and 0% for PD-(L)1-relapsed patients.
CONCLUSIONS
Durvalumab plus tremelimumab had a manageable safety profile, but the combination did not have efficacy after PD-(L)1 treatment failure.
简介
尽管一线免疫治疗方法是标准的，但对于先前接受程序性死亡蛋白-1 或程序性死亡配体-1（PD-[L]1）抑制剂治疗的非小细胞肺癌（NSCLC）患者，联合 CTLA-4 加 PD-[L]1 抑制的活性尚不清楚。这项 1b 期研究评估了在接受 PD-[L]1 单药治疗作为最近一线治疗的晚期 NSCLC 成人中，durvalumab 联合 tremelimumab 的安全性和疗效。
方法
2013 年 10 月 25 日至 2019 年 9 月 17 日期间，招募了 PD-[L]1 复发或难治性 NSCLC 患者。durvalumab 20mg/kg 加 tremelimumab 1mg/kg 静脉注射，每 4 周 1 次，共 4 次剂量，随后每 4 周 1 次，最多 9 次 durvalumab 单药治疗，治疗时间最长为 12 个月或直至疾病进展。主要终点包括盲法独立中心评估的根据实体瘤反应评价标准 1.1（RECIST v1.1）的安全性和客观缓解率（ORR）；次要终点为根据研究者评估的 RECIST v1.1 的 ORR；盲法独立中心评估和研究者评估的根据 RECIST v1.1 的缓解持续时间、疾病控制和无进展生存期；以及总生存期。
临床试验
gov 标识符：NCT02000947。
结果
PD-[L]1 难治性（n=38）和 PD-[L]1 复发（n=40）患者接受了治疗。最常见的治疗相关不良事件是疲劳（26.3%，PD-[L]1 难治性患者）和腹泻（27.5%，PD-[L]1 复发性患者）。22 例患者发生 3 至 4 级治疗相关不良事件。PD-[L]1 难治性患者中位随访时间为 43.6 个月，PD-[L]1 复发性患者为 41.2 个月。PD-[L]1 难治性患者的 ORR 为 5.3%（1 例完全缓解，1 例部分缓解），PD-[L]1 复发性患者的 ORR 为 0%。
结论
durvalumab 联合 tremelimumab 具有可管理的安全性特征，但在 PD-[L]1 治疗失败后，联合用药没有疗效。
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