複宏漢霖創新型抗HER2單抗HLX22 I期研究成果發表於Investigational New Drugs_研發動態_研發動態_研發創新_狗万醫藥-持續創新 樂享健康

2023-05-17

複宏漢霖創新型抗HER2單抗HLX22 I期研究成果發表於Investigational New Drugs

近日，複宏漢霖HLX22（創新型抗HER2單抗）針對HER2過表達的晚期實體(ti) 瘤的I期臨(lin) 床研究數據發表於(yu) 期刊Investigational New Drugs。研究結果顯示，HLX22在HER2過表達的晚期實體(ti) 瘤患者中具有良好的安全性和耐受性，為(wei) HLX22與(yu) 曲妥珠單抗等產(chan) 品聯合療法的開展奠定了基礎。


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HLX22為(wei) 複宏漢霖自AbClon, Inc.許可引進、並後續自主研發的靶向HER2的創新型單克隆抗體(ti) 。本次發表的研究為(wei) 一項開放標簽、劑量遞增、I期臨(lin) 床研究，旨在評估HLX22在標準療法無效或無法耐受治療的HER2陽性晚期實體(ti) 瘤患者中的安全性、耐受性、藥代動力學、藥效動力學和初步療效。本研究的主要終點為(wei) 安全性和HLX22的最大耐受劑量（MTD），次要終點包含藥代動力學、藥效動力學、免疫原性及初步療效。11名18-75歲之間的患者被分成三組，分別接受靜脈輸注不同劑量（3、10、25 mg/kg）的HLX22的治療，每三周一次。研究結果顯示，研究過程中未發生嚴(yan) 重不良事件和劑量限製毒性，HLX22的MTD為(wei) 25 mg/kg，每三周一次。全分析集人群的疾病控製率為(wei) 36.4%（95%CI：7.9%-64.8%），中位無進展生存期為(wei) 44.0天（95%CI：41.0天-170.0天）。


與(yu) 曲妥珠單抗類似，HLX22可結合在HER2的亞(ya) 結構域IV，但結合表位與(yu) 曲妥珠單抗有所不同，使得HLX22和曲妥珠單抗能夠同時與(yu) HER2結合，從(cong) 而產(chan) 生更強的HER2受體(ti) 阻斷效果。臨(lin) 床前研究表明，HLX22與(yu) 曲妥珠單抗聯合治療可抑製表皮生長因子（EGF）和HRG1（Histidine-Rich Glycoprotein 1）誘導的細胞增殖，增強體(ti) 外和體(ti) 內(nei) 的抗腫瘤活性。此次臨(lin) 床I期結果表明，HLX22具有良好的安全性和耐受性，為(wei) HLX22聯合曲妥珠單抗及化療的進一步開展提供了依據。目前，HLX22聯合漢曲優(you) ®（曲妥珠單抗，歐洲商品名：Zercepac®，澳大利亞(ya) 商品名：Tuzucip®和Trastucip®）及化療一線治療HER2陽性局部晚期/轉移性胃癌的II期臨(lin) 床試驗正在開展中。


公司圍繞HER2靶點已展開廣泛的產(chan) 品布局，自主開發的豐(feng) 富管線已覆蓋多款靶向HER2的抗體(ti) 生物藥包括漢曲優(you) 、HLX22、HLX11（帕妥珠單抗）。同時，抗體(ti) 研發過程積累的豐(feng) 富經驗也為(wei) 相關(guan) 雙特異性抗體(ti) 等新型抗體(ti) 的研發奠定了紮實的基礎，公司也正在積極探索更多創新藥物形式，開發出更多更高效的治療選擇。


關(guan) 於(yu) Investigational New Drugs

新型抗癌藥物開發是癌症研究領域發展最快的方向之一。Investigational New Drugs（影響因子：3.651）收錄內(nei) 容涵蓋所有常規研究領域及分支學科，為(wei) 開發抗癌新藥的科學家們(men) 提供了一個(ge) 藥物發現和最新研究成果快速發布的平台。期刊發表的論文受到醫學化學家、毒理學家、藥劑師、藥理學家、生物統計學家和臨(lin) 床腫瘤學家的廣泛關(guan) 注。

關(guan) 於(yu) 複宏漢霖

複宏漢霖（2696.HK）是一家國際化的創新生物製藥公司，致力於(yu) 為(wei) 全球患者提供可負擔的高品質生物藥，產(chan) 品覆蓋腫瘤、自身免疫疾病、眼科疾病等領域，已在中國上市5款產(chan) 品，在國際上市1款產(chan) 品，18項適應症獲批，3個(ge) 上市申請分別獲中國藥監局、美國FDA和歐盟EMA受理。自2010年成立以來，複宏漢霖已建成一體(ti) 化生物製藥平台，高效及創新的自主核心能力貫穿研發、生產(chan) 及商業(ye) 運營全產(chan) 業(ye) 鏈。公司已建立完善高效的全球創新中心，按照國際藥品生產(chan) 質量管理規範（GMP）標準進行生產(chan) 和質量管控，不斷夯實一體(ti) 化綜合生產(chan) 平台，其中，上海徐匯基地已獲得中國和歐盟GMP認證，鬆江基地（一）也已獲得中國GMP認證。


複宏漢霖前瞻性布局了一個(ge) 多元化、高質量的產(chan) 品管線，涵蓋20多種創新單克隆抗體(ti) ，並全麵推進基於(yu) 自有抗PD-1單抗H藥漢斯狀®的腫瘤免疫聯合療法。繼國內(nei) 首個(ge) 生物類似藥漢利康®（利妥昔單抗）、中國首個(ge) 自主研發的中歐雙批單抗藥物漢曲優(you) ®（曲妥珠單抗，歐洲商品名：Zercepac®，澳大利亞(ya) 商品名：Tuzucip®和Trastucip®）、漢達遠®（阿達木單抗）和漢貝泰®（貝伐珠單抗）相繼獲批上市，創新產(chan) 品漢斯狀®（斯魯利單抗）已獲批用於(yu) 治療微衛星高度不穩定（MSI-H）實體(ti) 瘤、鱗狀非小細胞肺癌和廣泛期小細胞肺癌，成為(wei) 全球首個(ge) 獲批一線治療小細胞肺癌的抗PD-1單抗，其食管鱗狀細胞癌適應症的上市注冊(ce) 申請也正在審評中。公司亦同步就16個(ge) 產(chan) 品在全球範圍內(nei) 開展30多項臨(lin) 床試驗，對外授權全麵覆蓋歐美主流生物藥市場和眾(zhong) 多新興(xing) 市場。



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 biosesimilar). 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, biosestatistician 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 biosesimilar, HANQUYOU (trastuzumab for injection, trade name in Europe: Zercepac®; trade names in Australia: Tuzucip® and Trastucip®, the first China-developed mAb biosesimilar 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.


*圖片素材來源於(yu) Springer期刊數據庫官網

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