A phase 1b study of zilovertamab in combination with paclitaxel for locally advanced/unresectable or metastatic Her2-negative breast cancer

IF 6.1 1区 医学 Q1 ONCOLOGY Breast Cancer Research Pub Date : 2024-02-26 DOI:10.1186/s13058-024-01782-0
Rebecca A. Shatsky, Hemali Batra-Sharma, Teresa Helsten, Richard B. Schwab, Emily I. Pittman, Minya Pu, Elizabeth Weihe, Emanuela M. Ghia, Laura Z. Rassenti, Alfredo Molinolo, Betty Cabrera, James B. Breitmeyer, George F. Widhopf, Karen Messer, Catriona Jamieson, Thomas J. Kipps, Barbara A. Parker
{"title":"A phase 1b study of zilovertamab in combination with paclitaxel for locally advanced/unresectable or metastatic Her2-negative breast cancer","authors":"Rebecca A. Shatsky, Hemali Batra-Sharma, Teresa Helsten, Richard B. Schwab, Emily I. Pittman, Minya Pu, Elizabeth Weihe, Emanuela M. Ghia, Laura Z. Rassenti, Alfredo Molinolo, Betty Cabrera, James B. Breitmeyer, George F. Widhopf, Karen Messer, Catriona Jamieson, Thomas J. Kipps, Barbara A. Parker","doi":"10.1186/s13058-024-01782-0","DOIUrl":null,"url":null,"abstract":"Zilovertamab is a humanized monoclonal antibody targeting ROR1, an onco-embryonic antigen expressed by malignant cells of a variety of solid tumors, including breast cancer. A prior phase 1 study showed that zilovertamab was well tolerated and effective in inhibiting ROR1-signaling, which leads to activation of ERK1/2, NF-κB, and NRF2 target genes. This phase 1b study evaluated the safety and tolerability of zilovertamab with paclitaxel in patients with advanced breast cancer. Eligible patients had locally advanced, unresectable, or metastatic HER2− breast cancer with Eastern Cooperative Group performance status of 0–2 and without prior taxane therapy in the advanced setting. Study treatment included 600 mg of zilovertamab administered intravenously (IV) on Days 1 and 15 of Cycle 1 and then Day 1 of each 28-day cycle along with paclitaxel weekly at 80 mg/m2 IV. Study patients had received a median of 4 prior therapies (endocrine therapy + chemotherapy) for locally advanced, unresectable, or metastatic disease. No patient discontinued therapy due to toxicity ascribed to zilovertamab. Adverse events were consistent with the known safety profile of paclitaxel. Of 16 patients, 6 (38%) had a partial response, and 6/16 (38%) patients had stable disease as best tumor response. The combination of zilovertamab and paclitaxel was safe and well tolerated in heavily pre-treated advanced breast cancer patients. Further evaluation of ROR1 targeting in breast cancer patients with zilovertamab is warranted. Trial Registration: NCT02776917. Registered on ClinicalTrials.gov on 05/17/2016.","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":null,"pages":null},"PeriodicalIF":6.1000,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Breast Cancer Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13058-024-01782-0","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Zilovertamab is a humanized monoclonal antibody targeting ROR1, an onco-embryonic antigen expressed by malignant cells of a variety of solid tumors, including breast cancer. A prior phase 1 study showed that zilovertamab was well tolerated and effective in inhibiting ROR1-signaling, which leads to activation of ERK1/2, NF-κB, and NRF2 target genes. This phase 1b study evaluated the safety and tolerability of zilovertamab with paclitaxel in patients with advanced breast cancer. Eligible patients had locally advanced, unresectable, or metastatic HER2− breast cancer with Eastern Cooperative Group performance status of 0–2 and without prior taxane therapy in the advanced setting. Study treatment included 600 mg of zilovertamab administered intravenously (IV) on Days 1 and 15 of Cycle 1 and then Day 1 of each 28-day cycle along with paclitaxel weekly at 80 mg/m2 IV. Study patients had received a median of 4 prior therapies (endocrine therapy + chemotherapy) for locally advanced, unresectable, or metastatic disease. No patient discontinued therapy due to toxicity ascribed to zilovertamab. Adverse events were consistent with the known safety profile of paclitaxel. Of 16 patients, 6 (38%) had a partial response, and 6/16 (38%) patients had stable disease as best tumor response. The combination of zilovertamab and paclitaxel was safe and well tolerated in heavily pre-treated advanced breast cancer patients. Further evaluation of ROR1 targeting in breast cancer patients with zilovertamab is warranted. Trial Registration: NCT02776917. Registered on ClinicalTrials.gov on 05/17/2016.
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
齐洛韦坦单抗联合紫杉醇治疗局部晚期/不可切除或转移性 Her2 阴性乳腺癌的 1b 期研究
Zilovertamab是一种靶向ROR1的人源化单克隆抗体,ROR1是包括乳腺癌在内的多种实体瘤恶性细胞表达的一种肿瘤胚胎抗原。之前的一项1期研究表明,zilovertamab耐受性良好,能有效抑制ROR1信号传导,从而激活ERK1/2、NF-κB和NRF2靶基因。这项1b期研究评估了zilovertamab联合紫杉醇治疗晚期乳腺癌患者的安全性和耐受性。符合条件的患者均为局部晚期、无法切除或转移性 HER2-乳腺癌,东方合作组表现状态为 0-2,且既往未接受过晚期紫杉类药物治疗。研究治疗包括在第1周期的第1天和第15天静脉注射600毫克齐洛韦他单抗,然后在每个28天周期的第1天静脉注射紫杉醇,每周静脉注射80毫克/平方米。研究患者此前曾接受过中位数为4次的局部晚期、不可切除或转移性疾病治疗(内分泌治疗+化疗)。没有患者因齐洛韦坦单抗引起的毒性而中断治疗。不良反应与已知的紫杉醇安全性相符。在16名患者中,6名(38%)患者有部分反应,6/16(38%)患者的最佳肿瘤反应是病情稳定。在接受过大量预处理的晚期乳腺癌患者中,zilovertamab和紫杉醇的联合用药安全且耐受性良好。有必要进一步评估使用齐洛韦坦单抗对乳腺癌患者进行ROR1靶向治疗的效果。试验注册:NCT02776917。2016年5月17日在ClinicalTrials.gov上注册。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Breast Cancer Research
Breast Cancer Research 医学-肿瘤学
自引率
0.00%
发文量
76
期刊介绍: Breast Cancer Research is an international, peer-reviewed online journal, publishing original research, reviews, editorials and reports. Open access research articles of exceptional interest are published in all areas of biology and medicine relevant to breast cancer, including normal mammary gland biology, with special emphasis on the genetic, biochemical, and cellular basis of breast cancer. In addition to basic research, the journal publishes preclinical, translational and clinical studies with a biological basis, including Phase I and Phase II trials.
期刊最新文献
Impact of an online decision support tool for ductal carcinoma in situ (DCIS) using a pre-post design (AFT-25) Safety and efficacy of topical testosterone in breast cancer patients receiving ovarian suppression and aromatase inhibitor therapy A triple hormone receptor ER, AR, and VDR signature is a robust prognosis predictor in breast cancer Characteristics and transcriptional regulators of spontaneous epithelial–mesenchymal transition in genetically unperturbed patient-derived non-spindled breast carcinoma CAR expression in invasive breast carcinoma and its effect on adenovirus transduction efficiency
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1