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
{"title":"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。","authors":"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","doi":"10.1001/jamaoncol.2024.2145","DOIUrl":null,"url":null,"abstract":"<p><strong>Importance: </strong>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.</p><p><strong>Objective: </strong>To evaluate the safety and response rates of bintrafusp alfa in patients with recurrent or metastatic cervical cancer.</p><p><strong>Design, setting, and participants: </strong>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.</p><p><strong>Intervention: </strong>Patients received bintrafusp alfa, 1200 mg, intravenously once every 2 weeks.</p><p><strong>Main outcomes and measures: </strong>The primary end point was confirmed objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 by an independent review committee.</p><p><strong>Results: </strong>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%]).</p><p><strong>Conclusions and relevance: </strong>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.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT04246489.</p>","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":null,"pages":null},"PeriodicalIF":28.4000,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11273284/pdf/","citationCount":"0","resultStr":"{\"title\":\"Bintrafusp Alfa for Recurrent or Metastatic Cervical Cancer After Platinum Failure: A Nonrandomized Controlled Trial.\",\"authors\":\"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\",\"doi\":\"10.1001/jamaoncol.2024.2145\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Importance: </strong>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.</p><p><strong>Objective: </strong>To evaluate the safety and response rates of bintrafusp alfa in patients with recurrent or metastatic cervical cancer.</p><p><strong>Design, setting, and participants: </strong>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.</p><p><strong>Intervention: </strong>Patients received bintrafusp alfa, 1200 mg, intravenously once every 2 weeks.</p><p><strong>Main outcomes and measures: </strong>The primary end point was confirmed objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 by an independent review committee.</p><p><strong>Results: </strong>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%]).</p><p><strong>Conclusions and relevance: </strong>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.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT04246489.</p>\",\"PeriodicalId\":48661,\"journal\":{\"name\":\"Jama Oncology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":28.4000,\"publicationDate\":\"2024-07-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11273284/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Jama Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1001/jamaoncol.2024.2145\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"Biochemistry, Genetics and Molecular Biology\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Jama Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1001/jamaoncol.2024.2145","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
Bintrafusp Alfa for Recurrent or Metastatic Cervical Cancer After Platinum Failure: A Nonrandomized Controlled Trial.
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.
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.
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