Shanghai, China, May 14, 2024 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the investigational new drug application (IND) for the clinical trial of HLX78, also known as lasofoxifene, for the treatment of ER+/HER2- breast cancer harboring ESR1 mutation has been approved by the National Medical Products Administration (NMPA) to conduct clinical trials in China.
Breast cancer is the second most diagnosed cancer in the world, according to GLOBOCAN 2022. There were around 2.30 million new cases of breast cancer in 2022 globally, including more than 357,000 in China [1]. ER+ breast cancer comprises 60-70% of all breast cancers [2]. Endocrine therapy remains the mainstay treatment for ER+ breast cancer and the most widely used class of aromatase inhibitor (AI) has been recommended by the National Comprehensive Cancer Network (NCCN) and Chinese Society of Clinical Oncology (CSCO) guidelines to be the adjuvant and first-line standard of care for patients with ER+/HER2- breast cancer [3-4]. However, almost all patients treated with AIs develop primary or acquired resistance [5], with acquired mutations in the estrogen receptor α gene (ESR1) being the most prevalent (up to 40%). This is a significant mechanism of resistance to endocrine therapy [6]. Currently, there are limited treatment options for ER+/HER2- breast cancer with ESR1 mutations, and thus a large clinical need exists.
HLX78 (lasofoxifene) is an oral selective estrogen receptor modulator (SERM) licensed by Henlius from Sermonix Pharmaceuticals, Inc. that has demonstrated robust target engagement in ER+/HER2- breast cancer, particularly in the presence of ESR1 mutations. Currently, the phase 3 ELAINE-3 multi-regional clinical trial (NCT05696626) to evaluate lasofoxifene in ER+/HER2- breast cancer population harboring ESR1 mutation is enrolling subjects in countries and regions including the U.S., EU, Canada, and Singapore. In two completed Phase 2 clinal studies (ELAINE-1 and ELAINE-2), lasofoxifene has demonstrated anti-tumor activity against tumors with ESR1 mutations as monotherapy and in combination with a CDK4/6 inhibitor [7-8]. Lasofoxifene’s bioavailability and activity in mutations of the estrogen receptor could potentially hold promise for patients who have acquired endocrine resistance due to ESR1 mutations, and, if approved, play a critical role in the precision medicine treatment of advanced ER+ breast cancer.
Fully leveraging the global research and development platform, Henlius has built a diversified product pipeline in monoclonal antibodies, bispecific antibodies, and antibody-drug conjugates (ADC). Looking forward, Henlius will continue to focus on unmet clinical needs and leverage its integrated platform, further strengthening the in-licensing and collaboration on external innovative assets and bringing more high-quality and affordable therapies to patients worldwide.
【Reference】
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[3] 《中国临床肿瘤学会（CSCO）乳腺癌诊疗指南2023》
[4] NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V.5.2023
[5] Rozeboom B, Dey N, De P. ER+ metastatic breast cancer: past, present, and a prescription for an apoptosis-targeted future. Am J Cancer Res. 2019;9(12):2821-2831. Published 2019 Dec 1.
[6] Spoerke JM, Gendreau S, Walter K, et al. Heterogeneity and clinical significance of ESR1 mutations in ER-positive metastatic breast cancer patients receiving fulvestrant. Nat Commun. 2016;7:11579. Published 2016 May 13. doi:10.1038/ncomms11579
[7] Goetz MP, Bagegni NA, Batist G, et al. Lasofoxifene versus fulvestrant for ER+/HER2- metastatic breast cancer with an ESR1 mutation: results from the randomized, phase II ELAINE 1 trial. Ann Oncol. 2023;34(12):1141-1151. doi:10.1016/j.annonc.2023.09.3104
[8] S. Damodaran, C.C. O’Sullivan, A. Elkhanany, I.C. Anderson, M. Barve, S. Blau, M.A. Cherian, J.A. Peguero, M.P. Goetz, P.V. Plourde, D.J. Portman, H.C.F. Moore, Open-label, phase II, multicenter study of lasofoxifene plus abemaciclib for treating women with metastatic ER+/HER2− breast cancer and an ESR1 mutation after disease progression on prior therapies: ELAINE 2. Ann Oncol. 2023;34(12):1131-1140. doi:10.1016/j.annonc.2023.09.3103.