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

Pin Zhang; Lin Wang; Yueying Zhen; Zhihong Wang; Hesheng Zhang; Richard Jones; Binghe Xu

doi:10.21147/j.issn.1000-9604.2024.01.05

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

Chin J Cancer Res. 2024 Feb 29;36(1):46-54. doi: 10.21147/j.issn.1000-9604.2024.01.05.

Authors

Pin Zhang¹, Lin Wang¹, Yueying Zhen², Zhihong Wang², Hesheng Zhang², Richard Jones², Binghe Xu¹

Affiliations

¹ 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.
² Tianjin Hemay Pharmaceutical Co., LTD, Tianjin 300308, China.

PMID: 38455366
PMCID: PMC10915640
DOI: 10.21147/j.issn.1000-9604.2024.01.05

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).

Keywords: Advanced breast cancer; HER2-positive; Hemay022; first-in-human trial.

Associated data

ClinicalTrials.gov/NCT05122494