胆道癌是罕见的、异质性的癌症，预后不良。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”）和能够阻断PD-L1的人源IgG1 mAb融合而成，用于局部晚期或转移性化学治疗难治性胆道癌患者的研究。此多中心、单臂、开放标记、2期研究 (NCT03833661) 招募对铂类治疗敏感的局部晚期或转移性胆道癌患者，接受1200 mg银屑病混合物每2周一次静脉注射治疗。主要终点是根据IRC评估确认的根据RECIST 1.1的客观反应。次要终点包括持久性反应率、安全性、PFS和OS。在2019年3月至2020年1月之间，共招募了159名患者，中位随访时间为16.1（范围为0.0-19.3）个月；17名患者（10.7%；95% CI，6.4%-16.6%）取得了客观反应。中位持续反应时间为10.0（范围为1.9-15.7）个月；10名患者（6.3%；95% CI，3.1%-11.3%）具有良好的反应（≥6个月）。中位PFS为1.8个月（95% CI，1.7-1.8个月）；中位OS为7.6个月（95% CI，5.8-9.7个月）。OS率为57.9%（6个月）和38.8%（12个月）。26.4%的患者发生了≥3级不良事件，其中包括1例治疗相关死亡（肝功能衰竭）。常见的≥3级不良事件包括贫血（3.8％）、瘙痒（1.9％）和转氨酶升高（1.9％）。尽管该研究未达到预先设定的主要终点，但Bintrafusp alfa在难治性癌症的二线治疗中表现出临床活性，具有持久性的反应，并且不良反应可控。版权所有 ©2023 The Author(s)， Wolters Kluwer Health, Inc. 发表。

Biliary tract cancers are rare, heterogeneous cancers with poor prognosis. 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 IgG1 mAb blocking PD-L1, was evaluated in patients with locally advanced/metastatic chemorefractory biliary tract cancers.This multicenter, single-arm, open-label, phase 2 study (NCT03833661) enrolled adults with locally advanced or metastatic biliary tract cancer that was intolerant to or had failed first-line systemic platinum-based chemotherapy. Patients received 1200 mg bintrafusp alfa intravenously Q2W. Primary endpoint was confirmed objective response according to RECIST 1.1 assessed by IRC. Secondary endpoints included DOR, durable response rate, safety, PFS, and OS.Between March 2019 and January 2020, 159 patients were enrolled. Median follow-up was 16.1 (range, 0.0-19.3) months; 17 patients (10.7%; 95% CI, 6.4% -16.6%) achieved objective response. Median DOR was 10.0 (range, 1.9-15.7) months; 10 patients (6.3%; 95% CI, 3.1%- 11.3%) had a durable response (≥6 mo). Median PFS was 1.8 months (95% CI, 1.7-1.8 mo); median OS was 7.6 months (95% CI, 5.8-9.7 mo). OS rates were 57.9% (6-month) and 38.8% (12-month). Grade ≥3 AEs occurred in 26.4% of patients, including one treatment-related death (hepatic failure). Frequent grade ≥3 adverse events included anemia (3.8%), pruritus (1.9%), and increased alanine aminotransferase (1.9%).Although this study did not meet its prespecified primary endpoint, bintrafusp alfa demonstrated clinical activity as second-line treatment in this hard-to-treat cancer, with durable responses and a manageable safety profile.Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.