Spira Alexander, Awada Ahmad, Isambert Nicolas, Lorente David, Penel Nicolas, Zhang Yue, Ojalvo Laureen S, Hicking Christine, Rolfe P Alexander, Ihling Christian, Dussault Isabelle, Locke George, Borel Christian
Department of Medical Oncology, Virginia Cancer Specialists, Fairfax, VA, United States.
US Oncology Research, The Woodlands, TX, United States.
Front Oncol. 2022 Dec 8;12:981940. doi: 10.3389/fonc.2022.981940. eCollection 2022.
We report the clinical activity, safety, and identification of a predictive biomarker for bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGFβRII (a TGF-β "trap") fused to a human IgG1 mAb blocking PD-L1, in patients with advanced triple-negative breast cancer (TNBC).
In this expansion cohort of a global phase 1 study, patients with pretreated, advanced TNBC received bintrafusp alfa 1200 mg every 2 weeks intravenously until disease progression, unacceptable toxicity, or withdrawal. The primary objective was confirmed best overall response by RECIST 1.1 assessed per independent review committee (IRC).
As of May 15, 2020, a total of 33 patients had received bintrafusp alfa, for a median of 6.0 (range, 2.0-48.1) weeks. The objective response rate was 9.1% (95% CI, 1.9%-24.3%) by IRC and investigator assessment. The median progression-free survival per IRC was 1.3 (95% CI, 1.2-1.4) months, and median overall survival was 7.7 (95% CI, 2.1-10.9) months. Twenty-five patients (75.8%) experienced treatment-related adverse events (TRAEs). Grade 3 TRAEs occurred in 5 patients (15.2%); no patients had a grade 4 TRAE. There was 1 treatment-related death (dyspnea, hemolysis, and thrombocytopenia in a patient with extensive disease at trial entry). Responses occurred independently of PD-L1 expression, and tumor RNAseq data identified as a potential biomarker of response.
Bintrafusp alfa showed clinical activity and manageable safety in patients with heavily pretreated advanced TNBC. as identified as a potential predictive biomarker of response.
NCT02517398.
我们报告了在晚期三阴性乳腺癌（TNBC）患者中，bintrafusp alfa（一种由转化生长因子β受体II（TGF-β“陷阱”）的细胞外结构域与人源化IgG1单克隆抗体（可阻断PD-L1）融合而成的首创双功能融合蛋白）的临床活性、安全性以及预测生物标志物的鉴定。
在这项全球1期研究的扩展队列中，经预处理的晚期TNBC患者每2周静脉注射1200 mg bintrafusp alfa，直至疾病进展、出现不可接受的毒性或停药。主要目标是由独立审查委员会（IRC）根据RECIST 1.1评估确认的最佳总体缓解率。
截至2020年5月15日，共有33例患者接受了bintrafusp alfa治疗，中位治疗时间为6.0（范围2.0 - 48.1）周。根据IRC和研究者评估，客观缓解率为9.1%（95%置信区间，1.9% - 24.3%）。IRC评估的中位无进展生存期为1.3（95%置信区间，1.2 - 1.4）个月，中位总生存期为7.7（95%置信区间，2.1 - 10.9）个月。25例患者（75.8%）发生了治疗相关不良事件（TRAEs）。3级TRAEs发生在5例患者（15.2%）中；无患者发生4级TRAEs。有1例治疗相关死亡（入组时患有广泛疾病的1例患者出现呼吸困难、溶血和血小板减少）。缓解的发生与PD-L1表达无关，肿瘤RNA测序数据确定 [此处原文缺失具体内容] 为潜在的反应生物标志物。
Bintrafusp alfa在经过大量预处理的晚期TNBC患者中显示出临床活性和可管理的安全性。 [此处原文缺失具体内容] 被确定为潜在的反应预测生物标志物。
NCT02517398。
