Abstract PO4-04-01: Antitumor activity and safety of sacibertinib (Hemay022) in combination with endocrine therapy in patients with ER and HER2 both positive metastatic breast cancer: A phase Ib study

Abstract

Abstract Abstract PURPOSE Sacibertinib (Hemay022) is a novel irreversible tyrosine kinase inhibitor (TKI) blocking epidermal growth factor receptor and human epidermal growth factor receptor 2 (HER2). This study aimed to explore the safety and efficacy of sacibertinib plus endocrine therapy in patients with estrogen receptor-positive ( PATIENTS AND METHODS Using a phase 1b 3+3 dose escalation and expansion study design, patients with ER+/HER2+ MBC were treated with sacibertinib (200mg-500mg daily) plus endocrine therapy including exemestane, letrozole, fulvestrant. The safety, pharmacokinetic and clinical efficacy, including objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR) and progression-free survival (PFS) were assessed. RESULTS A total of 55 ER+/HER2+ MBC patients pretreated with chemotherapy and anti-HER2 therapy were enrolled in the study between March, 2018 and July, 2021. The incidence of ORR ranged from 17.6% to 42.9%, DCR ranged from 63.0% to 86.8%, CBR ranged from 42.3% to 69.7%, and the overall median PFS was 9.0 (95% CI, 5.5 ~ 11.00) months. In the 400 mg Sacibertinib plus exemestane cohort (N = 18), ORR was 38.9% (7/18), DCR was 72.2%(13/18), CBR was 66.7%(12/18), and median PFS was 8.9 months; In the 500 mg Sacibertinib plus exemestane cohort (N = 12), ORR was 25.0%(3/12), DCR was 100.0%(12/12), CBR was 50.0%(6/12), and median PFS was 9.0 months. The ORR, CBR, and DCR were better in the 400 mg and above dose cohorts than in the 200 mg and 300 mg cohorts. The DCR of the 500 mg combined with exemestane cohort was better than that of the other dose cohorts. Sacibertinib plus endocrine therapy was well-tolerated without dose-limiting toxicities. The most frequent grade 3 adverse events included diarrhoea (9.1%), leucopenia(5.5%), neutropenia (3.6%). One (1.8%) had grade 4 hydropericardium. CONCLUSION Sacibertinib plus endocrine therapy had a favorable safety profile and antitumor activity in patients with ER+/HER2+ MBC, 400-500mg daily showed more efficacy, supporting further assessment in randomized studies. This figure showed response of Sacibertinib plus endocrine therapy in ER+/HER2+ metastatic breast cancer. Citation Format: Hui-Ping Li, Qingyuan Zhang, Ruyan Zhang, Yaxin Liu, Xianjun Hu. Antitumor activity and safety of sacibertinib (Hemay022) in combination with endocrine therapy in patients with ER and HER2 both positive metastatic breast cancer: A phase Ib study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-04-01.