University of Arkansas Medical Sciences, Little Rock.
Union Hospital Tongji Medical College Huazhong University of Science and Technology, Wuhan, Hubei, China.
JAMA Oncol. 2024 Sep 1;10(9):1204-1211. doi: 10.1001/jamaoncol.2024.2145.
Cervical cancer is a common and lethal cancer worldwide. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the human transforming growth factor β receptor II (or transforming growth factor β trap) fused via a flexible linker to the C-terminus of each heavy chain of an immunoglobulin G1 antibody blocking programmed cell death 1 ligand 1.
To evaluate the safety and response rates of bintrafusp alfa in patients with recurrent or metastatic cervical cancer.
DESIGN, SETTING, AND PARTICIPANTS: This phase 2 nonrandomized controlled trial evaluated bintrafusp alfa monotherapy in patients with recurrent or metastatic cervical cancer with disease progression during or after platinum-based chemotherapy. Data were collected from March 2020 to February 2022.
Patients received bintrafusp alfa, 1200 mg, intravenously once every 2 weeks.
The primary end point was confirmed objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 by an independent review committee.
At data cutoff, 146 of 203 screened patients received 1 or more doses of bintrafusp alfa; of these, the median (range) age was 53 (24-79) years. The study met its primary end point of a 95% CI above the objective response rate benchmark of 15%, with a confirmed objective response rate of 21.9% (95% CI, 15.5-29.5) per the independent review committee. Of these patients, 19 (59.4%) had a durable response of 6 months or more. At data cutoff, responses were ongoing in 13 of 32 responders (40.6%). The most common treatment-related adverse events were anemia (25 [17.1%]), rash (21 [14.4%]), hypothyroidism (15 [10.3%]), and pruritus (15 [10.3%]). Any-cause adverse events of special interest included anemia (82[56.2%]), bleeding events (81 [55.5%]), and immune-related adverse events (49 [33.6%]).
This phase 2 nonrandomized controlled trial of bintrafusp alfa met its primary end point, which may support the potential of a bispecific therapy targeting transforming growth factor β and programmed cell death 1 ligand 1 in patients with recurrent or metastatic cervical cancer.
ClinicalTrials.gov Identifier: NCT04246489.
宫颈癌是一种常见且致命的全球癌症。Bintrafusp alfa 是一种首创的双功能融合蛋白，由人转化生长因子 β 受体 II 的细胞外结构域（或转化生长因子 β 陷阱）通过柔性接头融合到每个重链的 C 末端组成，阻断程序性细胞死亡 1 配体 1。
评估 bintrafusp alfa 在复发性或转移性宫颈癌患者中的安全性和反应率。
设计、设置和参与者：这项 2 期非随机对照试验评估了 bintrafusp alfa 单药治疗在复发性或转移性宫颈癌患者中的疗效，这些患者在铂类化疗期间或之后疾病进展。数据收集于 2020 年 3 月至 2022 年 2 月。
患者接受 bintrafusp alfa，1200mg，每 2 周静脉注射一次。
主要终点是独立审查委员会根据实体瘤反应评估标准 1.1 版确认的客观缓解率。
在数据截止时，203 名筛查患者中有 146 名接受了 1 次或多次 bintrafusp alfa 治疗；其中，中位（范围）年龄为 53（24-79）岁。该研究达到了其主要终点，即独立审查委员会确认的客观缓解率超过 15%的置信区间，客观缓解率为 21.9%（95%CI，15.5-29.5）。这些患者中，19 名（59.4%）有 6 个月或更长时间的持久缓解。在数据截止时，32 名应答者中有 13 名（40.6%）的反应仍在继续。最常见的与治疗相关的不良事件是贫血（25[17.1%]）、皮疹（21[14.4%]）、甲状腺功能减退（15[10.3%]）和瘙痒（15[10.3%]）。特别关注的任何原因不良事件包括贫血（82[56.2%]）、出血事件（81[55.5%]）和免疫相关不良事件（49[33.6%]）。
这项 bintrafusp alfa 的 2 期非随机对照试验达到了主要终点，这可能支持针对转化生长因子 β 和程序性细胞死亡 1 配体 1 的双特异性治疗在复发性或转移性宫颈癌患者中的潜力。
ClinicalTrials.gov 标识符：NCT04246489。
