2024年12月24日，复宏汉霖（2696.HK）宣布，HLX78（lasofoxifene，拉索昔芬片）联合阿贝西利（CDK4/6 抑制剂）用于治疗既往接受过芳香化酶抑制剂（AI）治疗、雌激素受体α基因（ESR1）突变的雌激素受体阳性（ER+）、人表皮生长因子受体2阴性（HER2-）局部晚期或转移性乳腺癌患者的国际多中心III期临床研究（ELAINE-3研究，NCT05696626）完成中国首例患者给药。目前，该研究正同步于美国、加拿大、欧盟等国家和地区招募受试者。
乳腺癌是全球发病率第二高的癌症，据GLOBOCAN数据显示，2022年全球乳腺癌新发病例约230万，中国乳腺癌新发病例逾35.7万[1]。雌激素受体（Estrogen receptor，ER）阳性乳腺癌占乳腺癌总数的60%-70%[2]。内分泌治疗是ER+乳腺癌的主要治疗手段，其中最常使用的芳香化酶抑制剂（aromatase inhibitor，AI）已被美国国立综合癌症网络（NCCN）和中国临床肿瘤学会（CSCO）等指南推荐成为ER+/HER2-乳腺癌患者的辅助及一线标准治疗方法[3,4]，然而几乎所有经AI治疗的患者会产生原发性或获得性耐药[5]，其中ESR1获得性突变最为常见，高达40%，被认为是内分泌治疗重要耐药机制[6]，目前针对ESR1突变的ER+/HER2-乳腺癌治疗方案有限，存在较大治疗需求。
HLX78是公司自Sermonix Pharmaceuticals, Inc. 许可引进的一款临床在研口服选择性雌激素受体调节剂 (selective estrogen receptor modulator，SERM) ，在ESR1突变的ER+/HER2-转移性乳腺癌的治疗中具有强大的靶向治疗作用。在已完成的两项II期临床研究（ELAINE-1和ELAINE-2研究）中，针对ESR1突变肿瘤，lasofoxifene作为单药或联合CDK4/6抑制剂使用均展现出抗肿瘤活性[7-8]。从lasofoxifene对雌激素受体突变的生物利用度和药物活性来看，该候选药物有望为内分泌治疗后产生获得性耐药ESR1突变的患者群体带来希望，并有望在晚期ER+乳腺癌的精准医学治疗中发挥关键作用。
未来，公司也将继续以患者为中心，聚焦未满足的临床需求，垂直深耕乳腺癌领域领域，加快推进该项国际多中心临床试验进展，并以不断的创新与突破为更多病患带来更多质高价优的治疗方案。
【参考文献】
[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.
关于ELAINE-3研究
本研究是一项开放标签、随机、对照、多中心的III期研究，旨在比较HLX78联合阿贝西利和氟维司群联合阿贝西利治疗ER+/HER2–的局部晚期或转移性乳腺癌的男性和绝经前/后女性患者的有效性、安全性和耐受性，患者在接受芳香化酶抑制剂联合哌柏西利或瑞波西利作为一线内分泌治疗转移性疾病后出现疾病进展且携带ESR1基因突变。符合条件的受试者将以1:1的比例随机分配，接受HLX78（每日5毫克，口服）联合阿贝西利或氟维司群联合阿贝西利。本研究的主要目标是评估各治疗组的无进展生存期（PFS），评估采用盲态独立中心评估（BICR）基于实体瘤评价标准（RECIST）1.1进行。次要目标为评估其他终点，包括客观缓解率、总生存期、临床获益率、缓解持续时间、至缓解时间、至细胞毒性化疗时间、生活质量和安全性。
关于复宏汉霖
复宏汉霖（2696.HK）是一家国际化的创新生物制药公司，致力于为全球患者提供可负担的高品质生物药，产品覆盖肿瘤、自身免疫疾病、眼科疾病等领域，已有6款产品在中国获批上市，3款产品在国际获批上市，25项适应症获批，4个上市申请分别获中国药监局、美国FDA和欧盟EMA受理。自2010年成立以来，复宏汉霖已建成一体化生物制药平台，高效及创新的自主核心能力贯穿研发、生产及商业运营全产业链。公司已建立完善高效的全球创新中心，按照国际药品生产质量管理规范（GMP）标准进行生产和质量管控，不断夯实一体化综合生产平台，其中，公司商业化生产基地已相继获得中国、欧盟和美国GMP认证。
复宏汉霖前瞻性布局了一个多元化、高质量的产品管线，涵盖50多个分子，并全面推进基于自有抗PD-1单抗H药汉斯状®的肿瘤免疫联合疗法。截至目前，公司已获批上市产品包括国内首个生物类似药汉利康®（利妥昔单抗）、自主研发的中美欧三地获批单抗生物类似药汉曲优®（曲妥珠单抗，美国商品名：HERCESSI™，欧洲商品名：Zercepac®）、汉达远®（阿达木单抗）、汉贝泰®（贝伐珠单抗）以及汉奈佳®（奈拉替尼），此外，创新产品汉斯状®（斯鲁利单抗）已获批用于治疗微卫星高度不稳定（MSI-H）实体瘤、鳞状非小细胞肺癌、广泛期小细胞肺癌、食管鳞状细胞癌和非鳞状非小细胞肺癌，并成为全球首个获批一线治疗小细胞肺癌的抗PD-1单抗。公司亦同步就16个产品在全球范围内开展30多项临床试验，对外授权全面覆盖欧美主流生物药市场和众多新兴市场。
First Chinese Patient Dosed for Phase 3 MRCT on ER+/HER2- Breast Cancer of HLX78
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.
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.
About Henlius
Henlius (2696.HK) is a global biopharmaceutical company with the vision to offer high-quality, affordable and innovative biologic medicines for patients worldwide with a focus on oncology, autoimmune diseases and ophthalmic diseases. Up to date, 6 products have been launched in China, 3 have been approved for marketing in overseas markets, 25 indications are approved worldwide, and 4 marketing applications have been accepted for review in China, the U.S. and the EU, respectively. Since its inception in 2010, Henlius has built an integrated biopharmaceutical platform with core capabilities of high-efficiency and innovation embedded throughout the whole product life cycle including R&D, manufacturing and commercialization. It has established global innovation centre and Shanghai-based commercial manufacturing facilities certificated by China, the EU and U.S. GMP.
Henlius has pro-actively built a diversified and high-quality product pipeline covering over 50 molecules and has continued to explore immuno-oncology combination therapies with proprietary HANSIZHUANG (anti-PD-1 mAb) as the backbone. Apart from the launched products HANLIKANG (rituximab), the first China-developed biosimilar, HANQUYOU (trastuzumab, trade name: HERCESSI™ in the U.S., Zercepac® in Europe), a China-developed mAb biosimilar approved in China, Europe and U.S., HANDAYUAN (adalimumab) and HANBEITAI (bevacizumab), the innovative product HANSIZHUANG has been approved by the NMPA for the treatment of MSI-H solid tumors, squamous non-small cell lung cancer (sqNSCLC), extensive-stage small cell lung cancer (ES-SCLC), esophageal squamous cell carcinoma (ESCC) and non-small cell lung cancer (nsNSCLC), making it the world’s first anti-PD-1 mAb for the first-line treatment of SCLC. What’s more, Henlius has conducted over 30 clinical studies for 16 products, expanding its presence in major markets as well as emerging markets.
联系方式
媒体：PR@Henlius.com
投资者：IR@Henlius.com
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