国际化再迈坚实一步！复宏汉霖于美国完成H药用于一线治疗广泛期小细胞肺癌桥接研究的首例患者给药

内容来源于：复宏汉霖

2022年11月29日，复宏汉霖（2696.HK）宣布一项H药汉斯状^®（斯鲁利单抗）对比一线标准治疗阿替利珠单抗（PD-L1免疫抑制剂）的头对头桥接研究（NCT05468489）已在美国完成首例受试者给药。基于FDA针对H药治疗广泛期小细胞肺癌（ES-SCLC）递交上市申请的正向反馈及FDA C类咨询会议的讨论结果，公司拟招募200名美国受试者参与此项桥接临床试验，以评估H药汉斯状^®在美国ES-SCLC患者中的疗效。

2022年4月，公司宣布H药 汉斯状^®用于治疗小细胞肺癌（SCLC）获得美国食品药品监督管理局（FDA）授予的孤儿药资格认定（Orphan-drug Designation），有助于H药在美国研发、注册及商业化等方面享受一定的政策支持。在中国，H药一线治疗ES-SCLC适应症的上市申请已获得国家药品监督管理局（NMPA）受理。目前全球尚无一线治疗SCLC的抗PD-1单抗获批，H药有望成为全球首个一线治疗SCLC的抗PD-1单抗，填补未来五年PD-1抑制剂一线治疗小细胞肺癌的临床空白。

立足创新，精益求精

小细胞肺癌占肺癌总数的15%-20%，是肺癌中侵袭性最强的亚型，分为局限期小细胞肺癌（LS-SCLC）和ES-SCLC，恶性程度高、转移早、疾病进展迅速，总体预后不良。目前抗PD-L1单抗联合化疗已被最新版NCCN指南推荐为ES-SCLC一线治疗方案，但近年来多款PD-1产品在ES-SCLC领域接连折戟，未使全球ES-SCLC患者真正获益。

复宏汉霖已针对H药汉斯状^®用于一线治疗ES-SCLC在中国、土耳其、欧盟波兰、格鲁吉亚等多个国家开展一项国际多中心III期临床研究（ASTRUM-005）。该试验共开设128个试验中心，入组585例受试者，其中约31.5%为白人。ASTRUM-005临床试验结果于2022年美国临床肿瘤学会（ASCO）年会以口头报告方式首次发布，并于全球四大顶级医学期刊之一的《美国医学会杂志》（JAMA，影响因子：157.3）在线发表，成为全球首个登上JAMA主刊的小细胞肺癌免疫治疗临床研究。截至2021年10月22日，该试验斯鲁利单抗组的总人群中位总生存期（OS）达到15.4个月，刷新全球一线小细胞肺癌总生存期纪录的研究成果，并显示出良好的疗效和安全性。

广泛布局，加速全球开发

H药 汉斯状^®是复宏汉霖首个自主研发的创新型单抗，目前2项适应症获批上市，2项适应症上市申请获受理。自2022年3月获批上市以来，H药已在中国获批用于治疗微卫星高度不稳定（MSI-H）实体瘤和鳞状非小细胞肺癌，惠及逾9700名中国患者。围绕H药，复宏汉霖积极推进其与公司其他产品的协同以及与创新疗法的联合，相继获得中国、美国、欧盟等国家及地区的临床试验许可，在全球同步开展11项肿瘤免疫联合疗法临床试验，广泛覆盖肺癌、食管癌、头颈鳞癌和胃癌等适应症，全面覆盖肺癌一线治疗。截至目前，H药已于全球累计入组超3100人，其中包括ASTRUM-005在内的2项国际多中心临床试验入组白人的比例均超过30%，是拥有国际临床数据较多的抗PD-1单抗之一，有望支持H药在欧盟等海外市场的申报，为全球临床应用奠定基础。此次在美国开展桥接试验，也将进一步助推H药在全球的同步开发。

未来，公司也将继续以临床需求为核心，加快推进该项桥接临床试验进展及H药相关研究在全球范围的临床布局，并以不断的创新与突破为全球病患带来更多质高价优的生物药。

关于桥接研究（NCT05468489）

本研究为一项在既往未经治疗的广泛期小细胞肺癌（ES-SCLC）美国患者中开展的比较斯鲁利单抗联合化疗（卡铂-依托泊苷）及PD-L1免疫抑制剂阿替利珠单抗联合化疗（卡铂-依托泊苷）的有效性和安全性的随机、开放标签的临床研究。合格的患者按照1:1的比例随机分为两组，分别接受静脉输注斯鲁利单抗（300 mg）或阿替利珠单抗（1200 mg）联合化疗的治疗，每三周一次。本研究的主要目的为比较两种给药方案在既往未经治疗的美国ES-SCLC患者中的疗效。次要目的为评估斯鲁利单抗联合化疗的疗效、安全性、药代动力学及免疫原性。主要终点为总生存期（OS）。次要终点包括无进展生存期（PFS）、PFS2、客观缓解率（ORR）、持续缓解时间（DOR）、安全性、药代动力学特征和免疫原性。

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，15项适应症获批，4个上市注册申请获得中国药监局受理。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，其广泛期小细胞肺癌和食管鳞状细胞癌2项适应症的上市注册申请也正在审评中。公司亦同步就13个产品、11个免疫联合治疗方案在全球范围内开展20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。

First Patient dosed in a Head-to-Head First-Line Bridging Study of HANSIZHUANG for ES-SCLC treatment in the US

Shanghai, China, November 29, 2022 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first patient was dosed in NCT05468489, a bridging head-to-head trial in the United States comparing HANSIZHUANG (serplulimab), an innovative anti-PD-1 monoclonal antibody (mAb) independently developed by the company to standard of care Atezolizumab (anti-PD-L1 mAb). Based on the positive feedback of FDA Biologics license Application (BLA) submission for HANSIZHUANG for the treatment of extensive-stage small cell lung cancer (ES-SCLC) and the discussion results of the FDA's Class C consultation meeting, Henlius plans to recruit 100 pairs of US patients with ES-SCLC to evaluate the efficacy of HANSIZHUANG.

In April 2022, the company announced that US Food and Drug Administration (FDA) has granted Orphan-Drug Designation (ODD) for HANSIZHUANG for the treatment of small cell lung cancer (SCLC). The ODD granted by the FDA is beneficial for the continuous development of HANSIZHUANG and the enjoyment of certain policy support in terms of registration and commercialization in the United States. In China, the New Drug Application (NDA) of HANSIZHUANG in combination with chemotherapy for the first-line treatment of ES-SCLC has been accepted by the National Medical Products Administration (NMPA). At present, there is no anti-PD-1 mAb approved for the first-line treatment of SCLC worldwide. HANSIZHUANG is expected to become the world's first anti-PD-1 mAb for the first-line treatment of SCLC and to fill the clinical gap in the next five years.

Innovate to further advance

SCLC is the most aggressive subtype of lung cancer, accounting for 15% to 20% of all lung cancer cases. SCLC exhibit high malignancy, strong invasiveness, early metastasis, fast disease progression, and a poor prognosis. At present, anti-PD-L1 mAbs combined with chemotherapy have been recommended by clinical practice guidelines abroad as the first-line treatment for ES-SCLC, but there is no anti-PD-1 mAb approved worldwide, suggesting the need for more effective treatments in this patient population.

Henlius has conducted an international multi-centre phase 3 study of HANSIZHUANG plus chemotherapy as first-line treatment for patients with ES-SCLC. The study has set up a total of 128 sites in various countries including China, Turkey, Poland, and Georgia, and enrolled 585 subjects who were screened from 114 sites, among whom 31.5% were White. The results of ASTRUM-005 were presented for the first time in an oral report at the 2022 ASCO annual meeting, and ASTRUM-005 went on to become the first immunotherapy clinical study of SCLC to be published in The Journal of the American Medical Association (JAMA, impact factor of 157.3), one of the top four medical journals in the world. As of data cutoff for the interim analysis (October 22, 2021), median overall survival (OS) was significantly longer in the serplulimab group (15.4 months) than in the placebo group (10.9 months), forming a new world record. In addition, the study showed good safety and consistent efficacy over time.

Comprehensive Layout

HANSIZHUANG is the first innovative mAb developed by Henlius.  Up to date, 2 indications are approved for marketing in China, 2 NDAs have been accepted by the NMPA. Since launched in March 2022, HANSIZHUANG has been approved by the NMPA for the treatment of MSI-H solid tumours and squamous non-small cell lung cancer, benefiting more than 9,700 Chinese patients. Its synergy with in-house products of the company and innovative therapies are forging ahead. It has successively obtained clinical trial licenses in China, the United States, the European Union and other countries and regions to initiate 11 clinical trials on immuno-oncology combination therapies in a wide variety of indications, such as lung cancer, esophageal carcinoma, head and neck squamous cell carcinoma and gastric cancer, etc., and covering the full range of first-line treatments of lung cancers. As of now, HANSIZHUANG has enrolled more than 3,100 subjects around the world, and the proportion of White is over 30% in two MRCTs including ASTRUM-005. Such a large amount of global clinical data is also expected to bolster the marketing approval of HANSIZHUANG in overseas markets such as the European Union and to lay a foundation for global clinical application. The bridging trial carried out in the United States will also further promote the global development of HANSIZHUANG.

In the future, the company will continue to emphasize unmet clinical needs, actively promote the progress of this bridging study and the combination immunotherapy of serplulimab, offering high-quality, affordable, and innovative medicines to patients worldwide.

About NCT05468489

This randomised, open-label clinical study aims to compare the efficacy and safety of serplulimab with atezolizumab (anti-PD-L1 mAb) when combined with chemotherapy (carboplatin-etoposide) in previously untreated US patients with extensive-stage small cell lung cancer (ES-SCLC). Eligible patients will be randomised 1:1 to receive intravenous infusion of either serplulimab (300 mg) or atezolizumab (1200 mg) in combination with chemotherapy every 3 weeks. The primary objective of this study is to compare the efficacy of the two treatment regimens in previously untreated US ES-SCLC patients. Secondary objectives are to evaluate the efficacy, safety, pharmacokinetics, and immunogenicity of serplulimab in combination with chemotherapy. The primary endpoint is overall survival (OS). Secondary endpoints include progression-free survival (PFS), PFS2, objective response rate (ORR), duration of response (DOR), safety, pharmacokinetic characteristics, and immunogenicity.

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 approved for marketing in overseas markets, 15 indications approved worldwide, and 4 New Drug Applications (NDAs) accepted for review in China. 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; 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 tumours and squamous non-small cell lung cancer (sqNSCLC). Its NDAs for the treatment of extensive-stage small cell lung cancer (ES-SCLC) and esophageal squamous cell carcinoma (ESCC) are under review. What's more, Henlius has conducted over 20 clinical studies for 13 products and 11 combination therapies, expanding its presence in major markets as well as emerging markets.

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