摘要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).