復宏漢霖創新型抗HER2單抗HLX22 I期研究成果發表于Investigational New Drugs
近日，復宏漢霖HLX22（創新型抗HER2單抗）針對HER2過表達的晚期實體瘤的I期臨床研究數據發表于期刊Investigational New Drugs。研究結果顯示，HLX22在HER2過表達的晚期實體瘤患者中具有良好的安全性和耐受性，為HLX22與曲妥珠單抗等產品聯合療法的開展奠定了基礎。
點擊文末閱讀原文可獲取全文
HLX22為復宏漢霖自AbClon, Inc.許可引進、并后續自主研發的靶向HER2的創新型單克隆抗體。本次發表的研究為一項開放標簽、劑量遞增、I期臨床研究，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重不良事件和劑量限制毒性，HLX22的MTD為25 mg/kg，每三周一次。全分析集人群的疾病控制率為36.4%（95%CI：7.9%-64.8%），中位無進展生存期為44.0天（95%CI：41.0天-170.0天）。
與曲妥珠單抗類似，HLX22可結合在HER2的亞結構域IV，但結合表位與曲妥珠單抗有所不同，使得HLX22和曲妥珠單抗能夠同時與HER2結合，從而產生更強的HER2受體阻斷效果。臨床前研究表明，HLX22與曲妥珠單抗聯合治療可抑制表皮生長因子（EGF）和HRG1（Histidine-Rich Glycoprotein 1）誘導的細胞增殖，增強體外和體內的抗腫瘤活性。此次臨床I期結果表明，HLX22具有良好的安全性和耐受性，為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®（曲妥珠單抗，歐洲商品名：Zercepac®，澳大利亞商品名：Tuzucip®和Trastucip®）及化療一線治療HER2陽性局部晚期/轉移性胃癌的II期臨床試驗正在開展中。
公司圍繞HER2靶點已展開廣泛的產品布局，自主開發的豐富管線已覆蓋多款靶向HER2的抗體生物藥包括漢曲優、HLX22、HLX11（帕妥珠單抗）。同時，抗體研發過程積累的豐富經驗也為相關雙特異性抗體等新型抗體的研發奠定了扎實的基礎，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。
關于Investigational New Drugs
新型抗癌藥物開發是癌癥研究領域發展最快的方向之一。Investigational New Drugs（影響因子：3.651）收錄內容涵蓋所有常規研究領域及分支學科，為開發抗癌新藥的科學家們提供了一個藥物發現和最新研究成果快速發布的平臺。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、生物統計學家和臨床腫瘤學家的廣泛關注。
關于復宏漢霖
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
*圖片素材來源于Springer期刊數據庫官網
點擊鏈接可獲取全文
