A phase I study of Hemay022, an irreversible dual EGFR/HER2 tyrosine kinase inhibitor in Chinese patients with HER2-positive advanced breast cancer.

IF 7 2区 医学 Q1 ONCOLOGY Chinese Journal of Cancer Research Pub Date : 2024-02-29 DOI:10.21147/j.issn.1000-9604.2024.01.05
Pin Zhang, Lin Wang, Yueying Zhen, Zhihong Wang, Hesheng Zhang, Richard Jones, Binghe Xu
{"title":"A phase I study of Hemay022, an irreversible dual EGFR/HER2 tyrosine kinase inhibitor in Chinese patients with HER2-positive advanced breast cancer.","authors":"Pin Zhang, Lin Wang, Yueying Zhen, Zhihong Wang, Hesheng Zhang, Richard Jones, Binghe Xu","doi":"10.21147/j.issn.1000-9604.2024.01.05","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Hemay022 is a novel small-molecule and an irreversible tyrosine kinase inhibitor with the target of epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER2), which demonstrated anti-tumor activity in preclinical studies. This first-in-human study evaluated the safety, pharmacokinetics, tolerability and preliminary anti-tumor activity of Hemay022 in HER2-positive advanced breast cancer patients.</p><p><strong>Methods: </strong>Heavily pretreated patients with HER2-positive advanced breast cancer were assigned to eight dose cohorts in a 3+3 dose-escalation pattern at doses of 50-600 mg QD and 300 mg BID. Eligible patients were given a single dose of Hemay022 on d 1 in week 0, followed by once daily continuous doses for four weeks in 28-day cycles. Pharmacokinetic samples were obtained on d 1 and d 28. Clinical responses were assessed every eight weeks.</p><p><strong>Results: </strong>Twenty-eight patients with advanced breast cancer were treated with Hemay022. The most frequently reported drug-related adverse events were diarrhoea (85.7%), vomiting (28.6%), nausea (25.0%) and decreased appetite (17.9%). No grade 4 drug-related adverse events were reported. At 50-600 mg doses, steady state areas under the concentration-time curve and peak concentrations increased with doses. One patient achieved complete response (CR), and three achieved partial response (PR). The objective response rate (ORR) and disease control rate (DCR) were 14.3% and 46.4% in 28 patients, respectively. The median progression-free survival (PFS) was 3.98 months.</p><p><strong>Conclusions: </strong>Hemay022 at the dose of 500 mg once daily was well tolerated. The pharmacokinetic properties and encouraging anti-tumor activities of Hemay022 in advanced breast cancer patients warranted further evaluation of Hemay022 for treating breast cancer patients in the current phase III trial (No. NCT05122494).</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.0000,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10915640/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chinese Journal of Cancer Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21147/j.issn.1000-9604.2024.01.05","RegionNum":2,"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

Objective: Hemay022 is a novel small-molecule and an irreversible tyrosine kinase inhibitor with the target of epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER2), which demonstrated anti-tumor activity in preclinical studies. This first-in-human study evaluated the safety, pharmacokinetics, tolerability and preliminary anti-tumor activity of Hemay022 in HER2-positive advanced breast cancer patients.

Methods: Heavily pretreated patients with HER2-positive advanced breast cancer were assigned to eight dose cohorts in a 3+3 dose-escalation pattern at doses of 50-600 mg QD and 300 mg BID. Eligible patients were given a single dose of Hemay022 on d 1 in week 0, followed by once daily continuous doses for four weeks in 28-day cycles. Pharmacokinetic samples were obtained on d 1 and d 28. Clinical responses were assessed every eight weeks.

Results: Twenty-eight patients with advanced breast cancer were treated with Hemay022. The most frequently reported drug-related adverse events were diarrhoea (85.7%), vomiting (28.6%), nausea (25.0%) and decreased appetite (17.9%). No grade 4 drug-related adverse events were reported. At 50-600 mg doses, steady state areas under the concentration-time curve and peak concentrations increased with doses. One patient achieved complete response (CR), and three achieved partial response (PR). The objective response rate (ORR) and disease control rate (DCR) were 14.3% and 46.4% in 28 patients, respectively. The median progression-free survival (PFS) was 3.98 months.

Conclusions: Hemay022 at the dose of 500 mg once daily was well tolerated. The pharmacokinetic properties and encouraging anti-tumor activities of Hemay022 in advanced breast cancer patients warranted further evaluation of Hemay022 for treating breast cancer patients in the current phase III trial (No. NCT05122494).

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
Hemay022是一种不可逆的表皮生长因子受体/HER2酪氨酸激酶双重抑制剂,在中国HER2阳性晚期乳腺癌患者中的I期研究。
目的:Hemay022是一种新型小分子、不可逆的酪氨酸激酶抑制剂,以表皮生长因子受体(EGFR)/人表皮生长因子受体2(HER2)为靶点,在临床前研究中显示出抗肿瘤活性。这项首次人体研究评估了Hemay022在HER2阳性晚期乳腺癌患者中的安全性、药代动力学、耐受性和初步抗肿瘤活性。方法:HER2阳性晚期乳腺癌重度预处理患者以3+3剂量递增模式被分配到8个剂量组群,剂量为50-600毫克QD和300毫克BID。符合条件的患者在第0周的第1天服用单剂量的Hemay022,然后以28天为一个周期,连续服用4周,每天1次。在第 1 天和第 28 天采集药代动力学样本。临床反应每八周评估一次:28名晚期乳腺癌患者接受了Hemay022治疗。最常报告的药物相关不良事件是腹泻(85.7%)、呕吐(28.6%)、恶心(25.0%)和食欲下降(17.9%)。没有四级药物相关不良事件的报告。在 50-600 毫克剂量下,稳态浓度-时间曲线下面积和峰值浓度随剂量增加而增加。一名患者获得了完全应答(CR),三名患者获得了部分应答(PR)。28名患者的客观反应率(ORR)和疾病控制率(DCR)分别为14.3%和46.4%。中位无进展生存期(PFS)为3.98个月:结论:Hemay022的耐受性良好,剂量为500毫克,每天一次。Hemay022在晚期乳腺癌患者中的药代动力学特性和令人鼓舞的抗肿瘤活性证明,在目前的III期试验(NCT05122494号)中,有必要进一步评估Hemay022治疗乳腺癌患者的效果。
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
自引率
9.80%
发文量
1726
审稿时长
4.5 months
期刊介绍: Chinese Journal of Cancer Research (CJCR; Print ISSN: 1000-9604; Online ISSN:1993-0631) is published by AME Publishing Company in association with Chinese Anti-Cancer Association.It was launched in March 1995 as a quarterly publication and is now published bi-monthly since February 2013. CJCR is published bi-monthly in English, and is an international journal devoted to the life sciences and medical sciences. It publishes peer-reviewed original articles of basic investigations and clinical observations, reviews and brief communications providing a forum for the recent experimental and clinical advances in cancer research. This journal is indexed in Science Citation Index Expanded (SCIE), PubMed/PubMed Central (PMC), Scopus, SciSearch, Chemistry Abstracts (CA), the Excerpta Medica/EMBASE, Chinainfo, CNKI, CSCI, etc.
期刊最新文献
Efficacy and safety of dacomitinib as first-line treatment for advanced non-small cell lung cancer patients with epidermal growth factor receptor 21L858R mutation: A multicenter, case-series study in China. Immune status and combined immunotherapy progression in Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant tumors. Potential value of detection of minimal residual disease in colorectal cancer following radical resection. Tumor-derived DEFB1 induces immune tolerance by inhibiting maturation of dendritic cell and impairing CD8+ T cell function in esophageal squamous cell carcinoma. SOX11 as a potential prognostic biomarker in hepatocellular carcinoma linked to immune infiltration and ferroptosis.
×
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