近期，全球生物科学领域权威出版社Cell Press旗下的综合性医学旗舰期刊Med 2024年卷五第十期正式上线，复宏汉霖创新型抗HER2单抗HLX22联合汉曲优®（HLX02，曲妥珠单抗，美国商品名：HERCESSI™️，欧洲商品名：Zercepac®）和化疗用于一线治疗HER2阳性晚期或转移性胃/胃食管交界部（G/GEJ）癌的II期临床研究（HLX22-GC-201）荣登该期封面。该研究由上海高博肿瘤医院李进教授牵头开展。
本期Med的封面推荐语中强调了晚期胃癌治疗的迫切性及HLX22联合治疗的潜在益处，期刊指出：“胃癌是全球发病数第五多、致死数第四多的癌症。晚期胃癌的预后较差，愈发凸显了对更有效治疗策略的迫切需求。李进教授等研究者针对两种不同抗HER2单抗与XELOX联合作为HER2阳性晚期胃癌患者的一线治疗方案的疗效和安全性开展了II期临床研究。研究表明，该治疗方案显著延长了患者无进展生存期（PFS）并增强了抗肿瘤反应，且安全性良好，佐证了双HER2靶向的临床获益。” 同时，随刊刊登社评中指出，当前HLX22双靶联合治疗的II期临床研究已展现令人鼓舞的临床效果，其在HER2治疗领域的未来发展值得关注[1]。
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。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，促进HER2二聚体（HER2同源二聚体及HER2/EGFR异源二聚体）的内吞和降解，从而产生更强的受体阻断效果。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）和富组氨酸糖蛋白1（HRG1）诱导的细胞增殖，增强体外和体内的抗肿瘤活性，且HLX22的I期临床试验证实产品安全且可耐受[2]。
HLX22-GC-201是一项随机、双盲、多中心II期研究，旨在比较HLX22或安慰剂分别联合注射用曲妥珠单抗（HLX02）及化疗（XELOX）一线治疗HER2阳性的局部晚期/转移性胃癌患者的疗效和安全性的两阶段临床研究。第一阶段为安全导入期。第二阶段为一项随机、双盲、多中心II期临床研究，分为两个部分。在第一部分中，合格的受试者按1:1:1的比例随机分组，分别接受HLX22 25 mg/kg + HLX02 + XELOX（A组）、HLX22 15 mg/kg + HLX02 + XELOX（B组）或安慰剂 + HLX02 + XELOX（C组）治疗。主要终点是由独立影像学评估委员会（IRRC）基于RECIST v1.1评估的无进展生存期（PFS）和客观缓解率（ORR）。次要终点包括其他疗效指标和安全性。研究结果显示，在HLX02（曲妥珠单抗）联用化疗的基础上加入HLX22可明显改善HER2阳性G/GEJ癌患者一线治疗的效果，且安全性可控。HLX22-GC-201研究数据首次发布于2024年美国临床肿瘤学会胃肠道肿瘤研讨会（ASCO GI），其后该研究数据及数据更新亦分别获选发布于Med和2024年欧洲肿瘤学会胃肠道肿瘤研讨会（ESMO GI），多次验证了研究结果可靠性的同时，更进一步提升了该研究在学术界的影响力。
HLX22联合曲妥珠单抗及化疗一线治疗HER2阳性晚期胃癌的国际多中心III期临床研究已陆续在中国、美国和日本获得许可。未来，复宏汉霖将持续加码创新，以临床需求为先导，高效推进HLX22在全球的临床开发，为全球患者提供更多可负担、疗效更好的治疗方案。
【参考文献】
[1] Strickland MR, Klempner SJ. Dual HER2 inhibition: Is two better than one?. Med. 2024;5(10):1191-1193. doi:10.1016/j.medj.2024.07.008
[2] 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
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。
HLX22 Dual HER2 Blockade Therapy Featured on the Cover of Med
Recently, Volume 5, Issue 10 of Med, a flagship medical journal by Cell Press, has been published online. The front cover of the issue features HLX22-GC-201, a phase 2 study of HLX22, an innovative anti-HER2 monoclonal antibody (mAb), in combination with HANQUYOU (HLX02, trastuzumab, trade name: HERCESSI™️ in the U.S., Zercepac® in Europe) and chemotherapy for the first-line treatment of HER2-positive advanced gastric/gastroesophageal junction (G/GEJ) cancer. This study was led by Professor Jin Li from Shanghai GoBroad Cancer Hospital.
"Gastric cancer ranks as the fifth most prevalent cancer globally and the fourth leading cause of cancer-related mortality. The prognosis for advanced gastric cancer is poor, underscoring the urgent need for more effective treatment strategies. In this issue of Med, Li et al. conducted a phase 2 clinical study to explore the efficacy and safety of combining two different anti-HER2 antibodies plus XELOX as first-line therapy for patients with HER2-positive advanced gastric cancer." The editors emphasized the urgency of treating advanced gastric cancer and the potential benefits of HLX22 combined therapy. "The study reveals that the treatment regimen significantly extended progression-free survival and improved antitumor response in these patients, with manageable safety profiles, supporting the clinical benefits of dual HER2 blockade."
Additionally, the issue included an accompanying Viewpoint article, which highlighted that HLX22-GC-201 demonstrated encouraging objective response and progression-free survival, and future development of this combination in HER2+ G/GEJ cancer is worth continued attention [1].
HLX22 is an innovative anti-HER2 mAb introduced from AbClon, Inc. and further investigated and developed by Henlius. HLX22 can bind to HER2 subdomain IV at a binding site different from that of trastuzumab, which allows simultaneous binding of HLX22 and trastuzumab to HER2 dimers (HER2 homodimer and HER2/EGFR heterodimer) on tumour cell surface, thereby promoting the internalisation and HER2 dimer degradation. Pre-clinical studies showed that the co-treatment with HLX22 and trastuzumab inhibited cell proliferation induced by epidermal growth factor (EGF) and histidine-rich glycoprotein 1 (HRG1) and led to enhanced antitumour activity in vitro and in vivo. A phase 1 clinical trial of HLX22 demonstrates that HLX22 was well tolerated and had a favorable safety profile [2].
HLX22-GC-201 is a two-stage study aims to compare the efficacy and safety of HLX22 versus placebo in combination with trastuzumab injection (HLX02) and XELOX, as first-line therapy for HER2-positive locally advanced or metastatic gastric cancer patients. Stage 1 was a safety run-in stage while stage 2 was a randomised, double-blind, multi-centre, phase 2 study. Stage 2 was further divided into two parts. In part 1, eligible patients were randomised 1:1:1 to receive HLX22 (group A: HLX22, 25mg/kg; group B: HLX22, 15mg/kg) in combination with HLX02 and XELOX, or placebo in combination with HLX02 and XELOX (group C). The primary endpoints include progression-free survival (PFS) and objective response rate (ORR) assessed by independent radiological review committee (IRRC) per RECIST v1.1. The secondary objectives are to evaluate other efficacy endpoints, safety and tolerability. The results showed that the addition of HLX22 to HLX02 (trastuzumab) plus chemotherapy as first-line therapy improved efficacy in HER2-positive G/GEJ cancer patients with manageable safety.
Results from HLX22-GC-201 were first presented at the 2024 American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI). Updated results and study data and were subsequently presented at the 2024 ESMO Gastrointestinal Cancers Congress (ESMO GI) and on Med, respectively, which validated the reliability of the results and further enhanced the impact of the study in the academic community.
Investigational new drug (IND) applications have received regulatory approvals in China, the U.S. and Japan for a phase 3 international multi-centre clinical study of HLX22 in combination with trastuzumab and chemotherapy for the first-line treatment of HER2-positive advanced gastric cancer. Moving forward, Henlius will actively improve efficiency through innovations, with a particular focus on addressing the unmet medical needs, and efficiently promote the global clinical development of HLX22, so as to provide more high-quality and affordable therapies for patients worldwide.
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.
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媒体：PR@Henlius.com
投资者：IR@Henlius.com
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