Bintrafusp Alfa 对比帕博利珠单抗治疗初治、程序性死亡配体 1 高表达的晚期非小细胞肺癌患者：一项随机、开放标签、III 期临床试验。

Bintrafusp Alfa Versus Pembrolizumab in Patients With Treatment-Naive, Programmed Death-Ligand 1-High Advanced NSCLC: A Randomized, Open-Label, Phase 3 Trial.

机构信息

Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.

Seoul National University Bundang Hospital, Seongnam, Republic of Korea.

出版信息

J Thorac Oncol. 2023 Dec;18(12):1731-1742. doi: 10.1016/j.jtho.2023.08.018. Epub 2023 Aug 18.

DOI:10.1016/j.jtho.2023.08.018

PMID:37597750

Abstract

INTRODUCTION

Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGF-βRII (a TGF-β "trap") fused to a human immunoglobulin G1 monoclonal antibody blocking programmed death-ligand 1 (PD-L1), has exhibited clinical activity in a phase 1 expansion cohort of patients with PD-L1-high advanced NSCLC.

METHODS

This adaptive phase 3 trial (NCT03631706) compared the efficacy and safety of bintrafusp alfa versus pembrolizumab as first-line treatment in patients with PD-L1-high advanced NSCLC. Primary end points were progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1 per independent review committee and overall survival.

RESULTS

Patients (N = 304) were randomized one-to-one to receive either bintrafusp alfa or pembrolizumab (n = 152 each). The median follow-up was 14.3 months (95% confidence interval [CI]: 13.1-16.0 mo) for bintrafusp alfa and 14.5 months (95% CI: 13.1-15.9 mo) for pembrolizumab. Progression-free survival by independent review committee was not significantly different between bintrafusp alfa and pembrolizumab arms (median = 7.0 mo [95% CI: 4.2 mo-not reached (NR)] versus 11.1 mo [95% CI: 8.1 mo-NR]; hazard ratio = 1.232 [95% CI: 0.885-1.714]). The median overall survival was 21.1 months (95% CI: 21.1 mo-NR) for bintrafusp alfa and 22.1 months (95% CI: 20.4 mo-NR) for pembrolizumab (hazard ratio = 1.201 [95% CI: 0.796-1.811]). Treatment-related adverse events were higher with bintrafusp alfa versus pembrolizumab; grade 3-4 treatment-related adverse events occurred in 42.4% versus 13.2% of patients, respectively. The study was discontinued at an interim analysis as it was unlikely to meet the primary end point.

CONCLUSIONS

First-line treatment with bintrafusp alfa did not exhibit superior efficacy compared with pembrolizumab in patients with PD-L1-high, advanced NSCLC.

摘要

简介

Bintrafusp alfa 是一种首创的双功能融合蛋白，由 TGF-βRII 的细胞外结构域（TGF-β“陷阱”）与阻断程序性死亡配体 1（PD-L1）的人免疫球蛋白 G1 单克隆抗体融合而成，在 PD-L1 高的晚期 NSCLC 患者的 1 期扩展队列中显示出临床活性。

方法

这项适应性 3 期试验（NCT03631706）比较了 bintrafusp alfa 与 pembrolizumab 作为 PD-L1 高的晚期 NSCLC 患者一线治疗的疗效和安全性。主要终点是根据独立审查委员会的实体瘤反应评估标准 1.1 评估的无进展生存期和总生存期。

结果

患者（N=304）按 1:1 随机分配接受 bintrafusp alfa 或 pembrolizumab 治疗（n=152 例）。bintrafusp alfa 的中位随访时间为 14.3 个月（95%置信区间[CI]：13.1-16.0 mo），pembrolizumab 的中位随访时间为 14.5 个月（95%CI：13.1-15.9 mo）。独立审查委员会评估的无进展生存期在 bintrafusp alfa 和 pembrolizumab 组之间无显著差异（中位值=7.0 个月[95%CI：4.2 个月-NR] vs. 11.1 个月[95%CI：8.1 个月-NR]；风险比=1.232[95%CI：0.885-1.714]）。bintrafusp alfa 的中位总生存期为 21.1 个月（95%CI：21.1 mo-NR），pembrolizumab 的中位总生存期为 22.1 个月（95%CI：20.4 mo-NR）（风险比=1.201[95%CI：0.796-1.811]）。bintrafusp alfa 组的治疗相关不良事件发生率高于 pembrolizumab 组；分别有 42.4%和 13.2%的患者发生 3-4 级治疗相关不良事件。由于不太可能达到主要终点，该研究在中期分析时停止。