Zhang Pin, Wang Lin, Zhen Yueying, Wang Zhihong, Zhang Hesheng, Jones Richard, Xu Binghe
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Tianjin Hemay Pharmaceutical Co., LTD, Tianjin 300308, China.
Chin J Cancer Res. 2024 Feb 29;36(1):46-54. doi: 10.21147/j.issn.1000-9604.2024.01.05.
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.
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.
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.
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).
Hemay022是一种新型小分子不可逆酪氨酸激酶抑制剂，作用靶点为表皮生长因子受体（EGFR）/人表皮生长因子受体2（HER2），临床前研究显示其具有抗肿瘤活性。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、耐受性及初步抗肿瘤活性。
HER2阳性晚期乳腺癌的经大量预处理患者按3+3剂量递增模式分为8个剂量组，剂量为每日50 - 600 mg及每日两次300 mg。符合条件的患者在第0周第1天给予单剂量Hemay022，随后在28天周期内每日连续给药四周。在第1天和第28天采集药代动力学样本。每八周评估一次临床反应。
28例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为腹泻（85.7%）、呕吐（28.6%）、恶心（25.0%）和食欲下降（17.9%）。未报告4级药物相关不良事件。在50 - 600 mg剂量下，浓度 - 时间曲线下稳态面积和峰浓度随剂量增加。1例患者达到完全缓解（CR），3例达到部分缓解（PR）。28例患者的客观缓解率（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。
每日一次500 mg剂量的Hemay022耐受性良好。Hemay022在晚期乳腺癌患者中的药代动力学特性及令人鼓舞的抗肿瘤活性，使得有必要在当前的III期试验（编号NCT05122494）中进一步评估Hemay022治疗乳腺癌患者的效果。
