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2023-05-17

复宏汉霖创新型抗HER2单抗HLX22 I期研究成果发表于Investigational New Drugs

近日，复宏汉霖HLX22（创新型抗HER2单抗）针对HER2过表达的晚期实体瘤的I期临床研究数据发表于期刊Investigational New Drugs。研究结果显示，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，为HLX22与曲妥珠单抗等产品联合疗法的开展奠定了基础。


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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。本次发表的研究为一项开放标签、剂量递增、I期临床研究，旨在评估HLX22在标准疗法无效或无法耐受治疗的HER2阳性晚期实体瘤患者中的安全性、耐受性、药代动力学、药效动力学和初步疗效。本研究的主要终点为安全性和HLX22的最大耐受剂量（MTD），次要终点包含药代动力学、药效动力学、免疫原性及初步疗效。11名18-75岁之间的患者被分成三组，分别接受静脉输注不同剂量（3、10、25 mg/kg）的HLX22的治疗，每三周一次。研究结果显示，研究过程中未发生严重不良事件和剂量限制毒性，HLX22的MTD为25 mg/kg，每三周一次。全分析集人群的疾病控制率为36.4%（95%CI：7.9%-64.8%），中位无进展生存期为44.0天（95%CI：41.0天-170.0天）。


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。此次临床I期结果表明，HLX22具有良好的安全性和耐受性，为HLX22联合曲妥珠单抗及化疗的进一步开展提供了依据。目前，HLX22联合汉曲优®（曲妥珠单抗，欧洲商品名：Zercepac®，澳大利亚商品名：Tuzucip®和Trastucip®）及化疗一线治疗HER2阳性局部晚期/转移性胃癌的II期临床试验正在开展中。


公司围绕HER2靶点已展开广泛的产品布局，自主开发的丰富管线已覆盖多款靶向HER2的抗体生物药包括汉曲优、HLX22、HLX11（帕妥珠单抗）。同时，抗体研发过程积累的丰富经验也为相关双特异性抗体等新型抗体的研发奠定了扎实的基础，公司也正在积极探索更多创新药物形式，开发出更多更高效的治疗选择。


关于Investigational New Drugs

新型抗癌药物开发是癌症研究领域发展最快的方向之一。Investigational New Drugs（影响因子：3.651）收录内容涵盖所有常规研究领域及分支学科，为开发抗癌新药的科学家们提供了一个药物发现和最新研究成果快速发布的平台。期刊发表的论文受到医学化学家、毒理学家、药剂师、药理学家、生物统计学家和临床肿瘤学家的广泛关注。

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，已在中国上市5款产品，在国际上市1款产品，18项适应症获批，3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，上海徐汇基地已获得中国和欧盟GMP认证，松江基地（一）也已获得中国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20多种创新单克隆抗体，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。继国内首个生物类似药汉利康®（利妥昔单抗）、中国首个自主研发的中欧双批单抗药物汉曲优®（曲妥珠单抗，欧洲商品名：Zercepac®，澳大利亚商品名：Tuzucip®和Trastucip®）、汉达远®（阿达木单抗）和汉贝泰®（贝伐珠单抗）相继获批上市，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、鳞状非小细胞肺癌和广泛期小细胞肺癌，成为全球首个获批一线治疗小细胞肺癌的抗PD-1单抗，其食管鳞状细胞癌适应症的上市注册申请也正在审评中。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。



Phase I Clinical Results of Henlius HLX22, an innovative anti-HER2 mAb, Published in Investigational New Drugs


Recently, Henlius announced that the results of the phase 1 clinical trial of HLX22, an innovative anti-HER2 humanised monoclonal antibody (mAb) injection, were published in Investigational New Drugs. The results of this study demonstrated the safety and tolerability of HLX22, and laid the foundation to explore more therapies such as HLX22 combined with trastuzumab.


HLX22 is an innovative anti-HER2 mAb that was introduced from AbClon, Inc. and further researched and developed by Henlius. This first-in-human, phase 1 dose-escalation study aimed to evaluate the safety, tolerance, pharmacokinetics, pharmacodynamics, and preliminary efficacy of HLX22 in patients with HER2 overexpressing advanced solid tumours who had failed or were intolerant to standard therapies. The primary endpoints were safety and the maximum tolerated dose (MTD). Secondary endpoints included pharmacokinetics, pharmacodynamics, immunogenicity, and efficacy. 11 patients were enrolled to receive HLX22 once every 3 weeks at 3 (n = 5), 10 (n = 3), and 25 (n = 3) mg/kg doses. No serious adverse events or dose-limiting toxicities occurred during the treatment period, and the MTD was determined at 25 mg/kg once every 3 weeks. The disease control rate and median progression-free survival were 36.4% (95% confidence interval [CI], 7.9–64.8) and 44.0 days (95% CI, 41.0–170.0), respectively.


HLX22 can also 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 showed that the combination therapy of HLX22 and trastuzumab would inhibit 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 above phase I study showed that HLX22 was well tolerated in patients with advanced solid tumours overexpressing HER2 after failure of standard therapies, further supporting the investigation of HLX22 in combination of trastuzumab and chemotherapy. At present, the phase 2 clinical trial of HLX22 in combination with HANSIZHUANG (serplulimab) and HANQUYOU (trastuzumab, trade name in Europe: Zercepac®, trade names in Australia: Tuzucip® and Trastucip®) and chemotherapy as the first-line treatment for HER2-positive locally advanced/metastatic gastric cancer (GC) has been conducted.


 Up to now, Henlius has a well-established product pipeline in the area of anti-HER2 treatment including HANQUYOU, HLX22 and HLX11 (pertuzumab biosimilar). With regards to antibody technology, the company has built a solid foundation for discovering and developing bispecific/innovative antibodies to develop more biologics to provide patients with more effective therapies.


About Investigational New Drugs

The development of new anticancer agents is one of the most rapidly changing aspects of cancer research. Investigational New Drugs (Impact Factor：3.651) provides a forum for the rapid dissemination of information on new anticancer agents. The papers published are of interest to the medical chemist, toxicologist, pharmacist, pharmacologist, biostatistician and clinical oncologist. Investigational New Drugs provides the fastest possible publication of new discoveries and results for the whole community of scientists developing anticancer agents.


Investigational New Drugs cuts across all the usual lines or subdisciplines, providing a locus for the presentation of relevant investigations and the discussion of critical questions appropriate to the entire field of new anticancer drug development.

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, 5 products have been launched in China, 1 has been approved for marketing in overseas markets, 18 indications are approved worldwide, and 3 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 centers and Shanghai-based manufacturing facilities in line with global Good Manufacturing Practice (GMP), including Xuhui Plant certificated by China and the EU GMP and Songjiang First Plant certificated by China GMP.


Henlius has pro-actively built a diversified and high-quality product pipeline covering over 20 innovative monoclonal antibodies (mAbs) 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 for injection, trade name in Europe: Zercepac®; trade names in Australia: Tuzucip® and Trastucip®, the first China-developed mAb biosimilar approved both in China and Europe, 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) and extensive-stage small cell lung cancer (ES-SCLC), making it the world’s first anti-PD-1 mAb for the first-line treatment of SCLC. Its NDA for the treatment of esophageal squamous cell carcinoma (ESCC) is under review. What's more, Henlius has conducted over 30 clinical studies for 16 products, expanding its presence in major markets as well as emerging markets.


*图片素材来源于Springer期刊数据库官网

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