Bintrafusp Alfa for Recurrent or Metastatic Cervical Cancer After Platinum Failure: A Nonrandomized Controlled Trial.

IF 28.4 1区医学 Q1 Biochemistry, Genetics and Molecular Biology

Jama Oncology Pub Date : 2024-09-01 DOI:10.1001/jamaoncol.2024.2145

Michael Birrer, Guiling Li, Mayu Yunokawa, Jung-Yun Lee, Byoung Gie Kim, Christina Pimentel Oppermann, Qi Zhou, Shin Nishio, Aikou Okamoto, Xiaohua Wu, Linda Mileshkin, Ana Oaknin, Isabelle Ray-Coquard, Kosei Hasegawa, Genevieve Jehl, Yulia Vugmeyster, Sen Zhang, Marcis Bajars, Kan Yonemori

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引用次数: 0

Abstract

Importance: 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.

Objective: 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.

Intervention: Patients received bintrafusp alfa, 1200 mg, intravenously once every 2 weeks.

Main outcomes and measures: The primary end point was confirmed objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 by an independent review committee.

Results: 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%]).

Conclusions and relevance: 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.

Trial registration: ClinicalTrials.gov Identifier: NCT04246489.

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Bintrafusp Alfa 用于铂类药物治疗失败后的复发性或转移性宫颈癌：一项非随机对照试验。

重要性：宫颈癌是全球常见的致命癌症。Bintrafusp alfa是一种首创的双功能融合蛋白，由人类转化生长因子β受体II（或转化生长因子β捕获器）的胞外结构域通过柔性连接体与阻断程序性细胞死亡1配体1的免疫球蛋白G1抗体每条重链的C端融合而成：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：这项2期非随机对照试验评估了铂类化疗期间或之后疾病进展的复发性或转移性宫颈癌患者的bintrafusp alfa单药治疗。数据收集时间为2020年3月至2022年2月：患者接受1200毫克bintrafusp alfa静脉注射，每2周1次：主要终点是由独立审查委员会根据实体瘤反应评价标准1.1版确认的客观反应率：在数据截止时，203名筛查患者中有146人接受了1次或1次以上剂量的宾特法昔单抗；其中，中位（范围）年龄为53（24-79）岁。该研究达到了主要终点（95% CI 高于 15% 的客观反应率基准），经独立评审委员会确认，客观反应率为 21.9%（95% CI，15.5-29.5）。在这些患者中，有 19 人（59.4%）获得了 6 个月或更长时间的持久应答。在数据截止时，32 名应答者中有 13 人（40.6%）的应答仍在持续。最常见的治疗相关不良事件是贫血（25 [17.1%]）、皮疹（21 [14.4%]）、甲状腺功能减退（15 [10.3%]）和瘙痒（15 [10.3%]）。特别值得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%]）：bintrafusp alfa的这项2期非随机对照试验达到了主要终点，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的双特异性疗法在复发性或转移性宫颈癌患者中的应用潜力：试验注册：ClinicalTrials.gov Identifier：NCT04246489。

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来源期刊

Jama Oncology Medicine-Oncology

CiteScore

37.50

自引率

1.80%

发文量

423

期刊介绍： At JAMA Oncology, our primary goal is to contribute to the advancement of oncology research and enhance patient care. As a leading journal in the field, we strive to publish influential original research, opinions, and reviews that push the boundaries of oncology science. Our mission is to serve as the definitive resource for scientists, clinicians, and trainees in oncology globally. Through our innovative and timely scientific and educational content, we aim to provide a comprehensive understanding of cancer pathogenesis and the latest treatment advancements to our readers. We are dedicated to effectively disseminating the findings of significant clinical research, major scientific breakthroughs, actionable discoveries, and state-of-the-art treatment pathways to the oncology community. Our ultimate objective is to facilitate the translation of new knowledge into tangible clinical benefits for individuals living with and surviving cancer.