Shanghai, China, December 24, 2024 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first patient in China has been dosed in the international multi-centre Phase 3 clinical trial (ELAINE-3, NCT05696626) of HLX78 (oral lasofoxifene) in combination with abemaciclib (a CDK4/6 inhibitor) in patients with locally advanced or metastatic estrogen receptor-positive (ER+)/Human epidermal growth factor receptor 2-negative (HER2-) breast cancer who have disease progression on an aromatase inhibitor (AI) in combination with CDK4/6 inhibitor and have an estrogen receptor α gene (ESR1) mutation. ELAINE-3 is currently recruiting subjects in the United States, Canada, the European Union, in addition to other countries and regions.
Breast cancer is the second most diagnosed cancer in the world, according to GLOBOCAN 2022. There were around 2.3 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 in the advanced setting develop resistance[5], with ESR1 mutations being one of the most prevalent alterations, present in up to 40% of patients and 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 for Asia from Sermonix Pharmaceuticals, Inc. It has demonstrated robust target engagement in ER+/HER2- metastatic breast cancer, particularly in the presence of ESR1 mutations. In two completed Phase 2 clinal studies (ELAINE-1 and ELAINE-2), lasofoxifene has demonstrated anti-tumour activity against tumours 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.
In the future, Henlius will continue to adopt a patient-centric approach, focusing on unmet clinical needs. The company will delve deeply into the breast cancer field and expedite the development of the international multi-center clinical trial ELAINE-3, aiming to bring more high-quality, affordable, and innovative treatments to patients worldwide.
【Reference】
[1] Bray F, Laversanne M, Sung H, et al. CA Cancer J Clin. 2024: 1-35.
[2] Ignatiadis M, Sotiriou C. Luminal breast cancer: from biology to treatment[J]. Nat Rev Clin Oncol, 2013, 10(9): 494-506. doi: 10.1038/nrclinonc.2013.124.
[3] Chinese Society of Clinical Oncology (CSCO) Breast Cancer guidelines 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.
About ELAINE-3
This is a phase 3, open label, controlled, randomized, multicenter study comparing the efficacy, safety, and tolerability of the combination of lasofoxifene and abemaciclib with that of fulvestrant and abemaciclib for the treatment of men and pre- and postmenopausal women with locally advanced or metastatic ER+/HER2− breast cancer who have disease progression on an aromatase inhibitor in combination with either palbociclib or ribociclib as their first hormonal treatment for metastatic disease and who have an ESR1 mutation. Eligible participants will be randomized at 1:1 to receive lasofoxifene (5 mg/day, oral administration) combined with abemaciclib or fulvestrant combined with abemaciclib. The primary objective of this study is to evaluate the progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 as determined by blinded independent central review of each treatment arm. The secondary objectives are to evaluate other endpoints, including objective response rate, overall survival, clinical benefit rate, duration of response, time to response, time to cytotoxic chemotherapy, quality of life, and safety.