Abstract PO2-27-11: Antitumor efficacy and safety of sacibertinib (Hemay022) in combination with endocrine therapy in patients with ER+ and HER2+ metastatic breast cancer: A phase Ib study
Authors: Li Hui-Ping , Zhang Qingyuan , Zhang Ruyan , Liu Yaxin , Liu Chang , Hu Xianjun 
Published: May 2024

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 (ER+) and HER2-positive (HER2+) &gt;metastatic breast cancer (MBC). 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 (PK) and clinical efficacy, including objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR) and progression-free survival (PFS) were assessed. (Clinical Trials.gov identifier: NCT03308201). 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. Fifty-five patients were included in safety analysis and 51 patients were assessed for efficacy analysis. Sacibertinib plus endocrine therapy was well-tolerated without dose-limiting toxicities. The overall median PFS was 9.0 months [95% confidence interval (95% CI), 5.5 ~ 11.0]. The ORR, CBR, and DCR were better in the 400 mg and 500mg dose cohorts than in the 200 mg and 300 mg cohorts. The DCR of the 500 mg combined with the exemestane cohort was better than that of cohorts of other doses. 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 (95%CI, 2.7 ~ 16.4 ) ; In the 500 mg sacibertinib plus exemestane cohort (N = 12), ORR was 25.0% (3/12), DCR was 100%(12/12), CBR was 50.0%(6/12), and median PFS was 9.0 months (95%CI, 2.1~NA. Treatment-emergent AEs (TEAEs) were mostly within grades 1–2. The most frequent grade 3 TEAE was diarrhea (9.1%). One (1.8%) had grade 4 abnormal liver function. CONCLUSIONS Sacibertinib plus endocrine therapy had a favorable safety profile and antitumor activity in patients with ER+/HER2+ MBC, 400 -500mg sacibertinib daily showed more efficacy, supporting further assessment in randomized studies.

Summary of efficacy data(EAS)

NOTE. NA, not available (because cannot be calculated)

Treatment-Emergent Adverse Events Occurring in ≥ 10% of Patients in the Safety Population

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase;

Waterfall plot of best change rate in target-lesion size from baseline

Citation Format: Hui-Ping Li, Qingyuan Zhang, Ruyan Zhang, Yaxin Liu, Chang Liu, Xianjun Hu. Antitumor efficacy and safety of sacibertinib (Hemay022) in combination with endocrine therapy in patients with ER+ and HER2+ 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 PO2-27-11.