产品速递 | 复宏汉霖HLX22国际多中心III期临床试验在日本获许可，HER2双靶疗法一线治疗HER2阳性胃癌

近期，复宏汉霖获日本药品医疗器械综合机构（PMDA）许可开展针对公司创新型抗HER2单抗HLX22的国际多中心III期研究，拟用于联合曲妥珠单抗及化疗一线治疗HER2阳性晚期胃癌。此前，该研究的新药临床试验（IND）申请已获得中国国家药品监督管理局（NMPA）和美国食品药品监督管理局（FDA）许可。目前，全球尚无同类用于治疗HER2阳性胃癌的HER2双靶向疗法获批准上市。

迄今为止，胃癌/胃食管交界部（G/GEJ）癌依旧构成了一大全球健康问题。据GLOBOCAN数据显示，2022年全球约有100万新发病例^[1]。而在日本，G/GEJ的新发和死亡病例在全部恶性肿瘤中均位居第3位，其中2022年新发病例12.7万，死亡病例4.4万^[1]。多数G/GEJ癌患者确诊时已处于疾病晚期，总体预后不良，5年生存率仅为6%^[2,3]，这其中HER2 阳性患者占比约为12%-23%，且其预后较HER2阴性患者更差^[2,4]。目前，对于HER2阳性的局部晚期/转移性G/GEJ患者，其标准一线疗法为曲妥珠单抗联用化疗，针对PD-L1 阳性（PD-L1 CPS≥1）的患者，一些指南亦推荐进一步叠加联用免疫治疗，但持续疗效和预后仍有待进一步改善^[5]。

HLX22为复宏汉霖自AbClon, Inc.许可引进、并后续自主研发的靶向HER2的创新型单克隆抗体。与曲妥珠单抗类似，HLX22可结合在HER2的亚结构域IV，但结合表位与曲妥珠单抗有所不同，使得HLX22和曲妥珠单抗能够同时与HER2结合，从而产生更强的HER2受体阻断效果。临床前研究表明，HLX22与曲妥珠单抗联合治疗可抑制表皮生长因子（EGF）和HRG1（Histidine-Rich Glycoprotein 1）诱导的细胞增殖，增强体外和体内的抗肿瘤活性。此前，HLX22针对HER2过表达的晚期实体瘤的I期临床研究数据显示，HLX22在HER2过表达的晚期实体瘤患者中具有良好的安全性和耐受性^[6]。此外，HLX22联合汉曲优®（曲妥珠单抗，美国商品名：HERCESSI™️，欧洲商品名：Zercepac^®）治疗HER2阳性胃癌II期临床研究（HLX22-GC-201）结果相继于2024年美国临床肿瘤学会胃肠道肿瘤研讨会（ASCO GI）、欧洲肿瘤学会胃肠道肿瘤研讨会（ESMO GI）和Cell Press细胞出版社旗下的综合性医学旗舰期刊MED发布。研究结果显示，在HLX02（曲妥珠单抗）联用化疗的基础上加入HLX22可提高HER2阳性G/GEJ癌患者一线治疗的生存期和抗肿瘤反应，且安全性可控^[7-9]。

未来，公司也将继续秉持以患者为中心，聚焦未满足的临床需求，积极探索优化HER2阳性肿瘤联合疗法并推进HLX22的全球开发进程，为更多患者带去福音。

【参考文献】

[1] Bray F, Laversanne M, Sung H, et al. CA Cancer J Clin. 2024: 1-35.

[2] Ajani JA. et al. J Natl Compr Canc Netw 2022;20(2):167-92.

[3] Alsina M. et al. Nat Rev Gastroenterol Hepatol 2023;20(3):155-70.

[4] Gravalos C. et al. Ann Oncol 2008;19(9):1523-9.

[5] NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Gastric Cancer V.1.2024

[6] Zhu X, Ding Y, Wang Q, Yang G, Zhou L, Wang Q. HLX22, an anti-HER-2 monoclonal antibody, in patients with advanced solid tumors overexpressing human epidermal growth factor receptor 2: an open-label, dose-escalation, phase 1 trial. Invest New Drugs. 2023;41(3):473-482. doi:10.1007/s10637-023-01338-7

[7] Jin Li et al., HLX22 plus HLX02 and XELOX for first-line treatment of HER2-positive locally advanced or metastatic gastric/gastroesophageal junction cancer: A randomized, double-blind, multicenter phase 2 study.. JCO 42, 354-354(2024).DOI:10.1200/JCO.2024.42.3_suppl.354

[8] J. Li et al., 422P HLX22 plus HLX02 and XELOX as first-line therapy for HER2-positive advanced gastric/gastroesophageal junction cancer: Updated results from a randomized, double-blind phase II study, Annals of Oncology,Annals of Oncology (2024) 35 (suppl_1): S162-S204. 10.1016/annonc/annonc1482

[9] Li N, Qiu M, Zhang Y, et al. A randomized phase 2 study of HLX22 plus trastuzumab biosimilar HLX02 and XELOX as first-line therapy for HER2-positive advanced gastric cancer. Med. 2024;5(10):1255-1265.e2. doi:10.1016/j.medj.2024.06.004

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，24项适应症获批，3个上市申请分别获中国药监局和欧盟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、广泛期小细胞肺癌和食管鳞状细胞癌，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。

Henlius Receives Approval in Japan for Phase 3 MRCT of Dual HER2 Blockade Therapy on First-Line HER2+ GC

Recently, Henlius announced that the clinical trial notification (CTN) for phase 3 international multicenter clinical study of Henlius’ novel anti-HER2 mAb, HLX22, in combination with trastuzumab and chemotherapy for the first-line treatment of HER2-positive advanced gastric cancer has been permitted by Japan’s Pharmaceuticals and Medical Devices Agency (PMDA). The investigational new drug (IND) applications of this study have previously approved by National Medicinal Products Administration (NMPA) and the United States Food and Drug Administration (FDA). As of now, no similar dual HER2 blockade therapy for the treatment of HER2-positive gastric cancer has received approval for commercialization globally.

Until now, gastric/gastroesophageal junction (G/GEJ) cancer still constitutes a major global health problem. Globally, there were around 1 million cases in 2022^[1]. While in Japan, the incidence and mortality of G/GEJ rank third among all malignant tumors, and, in 2022, there were 127,000 new cases and 44,000 deaths ^[1]. G/GEJ cancer generally carries a poor prognosis since it is often diagnosed at an advanced stage, with a 5-year relative survival rate of only 6%^[2,3]. The reported rates of HER2 positivity in patients with gastric cancer range from 12% to 23%, and the prognosis for patients with HER2-positive disease used to be even worse than those with HER2-negative disease^[2-4]. Currently, for patients with HER2-positive locally advanced/metastatic G/GEJ cancer, the current standard first-line treatment is trastuzumab plus chemotherapy. Immunotherapies are recommended to be added for tumours with PD-L1 expression levels by CPS (Combined Positive Score) of greater than 1. However, the effectiveness and prognosis for these treatments need to be further improved^[5].

HLX22 is an innovative anti-HER2 mAb that was introduced from AbClon, Inc. and further researched and developed by Henlius. HLX22 can bind to HER2 subdomain IV at a different binding site from trastuzumab, which allows the simultaneous binding of HLX22 and trastuzumab to HER2. Pre-clinical studies have shown that the combination therapy of HLX22 and trastuzumab inhibits the cell proliferation induced by epidermal growth factor (EGF) and Histidine-Rich Glycoprotein 1 (HRG1) and enhance the antitumor activity in vitro and in vivo. The phase 1 clinical trial of HLX22 demonstrates that HLX22 is well tolerated and has good safety profiles. In January 2024, results from the phase 2 study of HLX22 combined with HANQUYOU (trastuzumab for injection, HLX02, HERCESSI™ in the U.S. and Zercepac^® in Europe) and chemotherapy for the first-line treatment of HER2-positive G/GEJ cancer was presented at the 2024 ASCO Gastrointestinal Cancers Symposium (ASCO GI), ESMO Gastrointestinal Cancers Congress (ESMO GI), and MED, a flagship clinical and translational research monthly journal by Cell Press, which showed that adding HLX22 to HLX02 (trastuzumab for injection) + XELOX improved survival and antitumor response in patients with HER2-positive G/GEJ cancer in the first-line setting, with a manageable safety profile^[7-9].

Moving forward, the company will continue to uphold a patient-centric approach, focus on unmet medical needs, and actively explore the optimization of combination therapies for HER2-positive cancer. This includes advancing clinical development for HLX22 to bring hope to more patients around the world.

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, 24 indications are approved worldwide, and 3 marketing applications have been accepted for review in China 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 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), HANBEITAI (bevacizumab) and HANNAIJIA (neratinib), the innovative product HANSIZHUANG has been approved by the NMPA for the treatment of MSI-H solid tumours, squamous non-small cell lung cancer (sqNSCLC) and extensive-stage small cell lung cancer (ES-SCLC), and esophageal squamous cell carcinoma (ESCC), 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