22年九月27日，由程颖先生加强组织领导的国际英文多学校科学实验——ASTRUM-005科学实验在世界八大一流药学期刊报刊中的一个的《USA药学会报刊》（JAMA，的影响细胞：157.3）高清在线说出，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。ASTRUM-005研究是复宏汉霖自主研发的抗PD-1单抗H药 汉斯状®（斯鲁利单抗）联合化疗一线治疗广泛期小细胞肺癌（ES-SCLC）的Ⅲ期临床研究，2022年ASCO年会程颖教授首次报告结果后，引起了全球同行的广泛关注，而今再度登上国际顶级学术舞台，体现了国际学术界的高度认可，彰显出中国研究者的智慧化和生物医药领域国际一流的自主创新实力和临床运营能力。
通信做者与首位做者、ASTRUM-005研发最主要研发者、吉林市省癌肿医院医生程颖讲师透露：
ASTRUM-005分析中斯鲁利单抗综合手术收获了现下多方面期小组织体细胞膜非小体细胞膜肝癌免疫系统系统体细胞膜标杆开展中最远的OS数据，与手术对比都可以变长4.五类月的生活工作，现今结束更低的HR：0.63，有时近些年调理作用和远期调理作用的数据统一，一同兼备好的安全保障性。这一分析初次得知了PD-1减弱剂综合手术类似才能有效改善多方面期小组织体细胞膜非小体细胞膜肝癌的生活工作，这也是尽我所能们中国国家大分析者带头的首家共性ES-SCLC习惯症免疫系统系统体细胞膜开展的国际级多核心临床实验Ⅲ期分析，有效充分的凸显了中国国家大分析者的能力。衷心谢谢大部分在该分析中进行贡献者的客户及父母的协调，也衷心谢谢另一个分析者的努力付出，这一分析为多方面期小组织体细胞膜非小体细胞膜肝癌标杆免疫系统系统体细胞膜开展绘制了新的每页，为各位客户带去福利。
OS达15.4个月，刷新一线小细胞肺癌总生存期纪录
小受损体细胞癌症（SCLC）约占癌症人数的15%，是癌症中外侵性中国最强的亚型，包含仅限期小受损体细胞癌症（LS-SCLC）和ES-SCLC。两种钢材共同体点是梭形细胞肿瘤方面较高、适当转移早、妇科疾病现况讯速，基本愈后缺陷。近年来，免疫力查检点治理和解决剂的展现为ES-SCLC方面的解决带动新小编希望，抗PD-L1单抗合作肺癌晚期放化疗已被国内的外专家要点推建为ES-SCLC第一线解决方式，比较肺癌晚期放化疗务必方面较上解决了的人总发展期，所以解决方面较相对应十分有限，仍还要更效果解决方式。
ASTRUM-005是一项在既往未接受过治疗的ES-SCLC患者中比较H药联合化疗及安慰剂联合化疗的临床有效性和安全性的随机、双盲、国际多中心、Ⅲ期临床研究，在中国、土耳其、欧盟波兰、格鲁吉亚等多个国家共开设128个试验中心，其中114个试验中心有受试者参与了筛选，共入组585例受试者，约31.5%为白人。截至2021年10月22日，本研究共入组的斯鲁利单抗组（n=389）和安慰剂组（n=196）中位随访时间为12.3个月。斯鲁利单抗组和安慰剂组的中位OS分别为15.4个月（95% CI 13.3–NE）和10.9个月（95% CI 10.0–14.3），风险比（HR）为0.63（95% CI 0.49–0.82；p<0.001）。两组的24个月总生存率分别为43.1%和7.9%。斯鲁利单抗组及安慰剂组经独立影像评估委员会（IRRC）依据RECIST v1.1评估的中位PFS分别为5.7和4.3个月（HR 0.48，95% CI 0.38–0.59）。安全性方面，斯鲁利单抗组的免疫相关不良事件（irAEs）发生率与已获批的PD-1/PD-L1单抗相似。
ASTRUM-005科研的完成是PD-1控剂型疗法ES-SCLC的关键超出，为本项科研，各国医疗耗材监查安全管理制度局（NMPA）已审批H药不错疗法ES-SCLC顺应症的挂牌出现报考；《CSCO小人体人体细胞非小人体细胞1.肺癌医疗服务白皮书（2022版）》也汇总斯鲁利单抗协同化疗药EC方案怎么写是 ES-SCLC不错疗法推见，为国ES-SCLC不错疗法提拱了更多的的的选择。不单单尽管，H入药于疗法SCLC于明年4月获美产品医疗耗材监查安全管理制度局（FDA）弃婴药资格证书认定书。互相，为FDA采取H药疗法ES-SCLC出具挂牌出现报考的领域反应及FDA C类联系大会的谈论报告，公司的将在美发动一笔桥接监床检验试验台，并拟于2026年Q1前在美出具一定的挂牌出现报考。阶段高度并未不错疗法SCLC的抗PD-1单抗新批，H药一般成高度首例不错疗法SCLC的抗PD-1单抗，补平之后五年左右PD-1控剂型不错疗法小人体人体细胞非小人体细胞1.肺癌的监床检验乱码。
十年后的中国，复宏汉霖将持续时间加仓自主创新，以临床实验业务需求服务至上导，延续优质地为全世界病患者带来了最好可负税、有效时间最好的手术治疗实施方案。
JAMA是竞争对手评定的新国际级全方位的管理性中分子生物学杂志，以利于中分子生物学的实验与的艺术或者优化公用清洁作为主要工作目标。自1883-5年累计出书开始，JAMA已是为中分子生物学和实验科技领域最具的导致到力的杂志一种，近年来的导致到指数公式为157.3。JAMA也是全当今发行日很广泛的全方位的管理性中分子生物学类杂志，包装印刷版关注数少于29万，电脑网络关注数少于160万，杂志网址的年访问共享量少于3400万，具备着强悍的交际网络互联网媒体的导致到力和新国际级新鲜事了网络互联网媒体的爆光率。
H药 汉斯状®为重组人源化抗PD-1单抗注射液（通用名：斯鲁利单抗注射液），是复宏汉霖首个自主研发的创新型单抗，目前1项适应症获批上市，3项适应症上市申请获受理，11项临床试验同步在全球开展。
明年5月，H药正式开启获准使用在方法微小行星的高度不平稳（MSI-H）实际瘤。环绕H药，复宏汉霖及时发展其与司其它新产品的协同管理及其与科技创新改善方式的协力，陆续才能得到国一个发展中国家、法国、欧盟一个发展中国家等一个发展中国家及的地方的医学冲击检验同意，在环球数据显示同步组织开展11项肺部肿瘤免役协力改善方式医学冲击检验，诸多复盖非小上皮内部肺肿瘤、食管癌、头颈鳞癌和食道癌等适应环境症，率先复盖非小上皮内部肺肿瘤专业的方法。直到现今，H药在国一个发展中国家、墨西哥、匈牙利、格鲁吉亚等一个发展中国家和的地方累记在组超3100人，至少2项国家多公司医学冲击检验入组白人的占比超越30%，是具有国家医学数据显示较多的抗PD-1单抗其一。H药协力肿瘤化疗专业的方法鳞状非小上皮内部非小上皮内部肺肿瘤（sqNSCLC）、诸多期小上皮内部非小上皮内部肺肿瘤（ES-SCLC）和食管鳞状上皮内部癌（ESCC）的NDA已才能得到NMPA审批，H药一般成為环球首例专业的方法SCLC的抗PD-1单抗。然而，该药评为《2022 CSCO小上皮内部非小上皮内部肺肿瘤口腔诊疗白皮书》身为ES-SCLC方法比较适合，重要性ES-SCLC的国家多公司医学论述ASTRUM-005成為环球首例登陆JAMA的小上皮内部非小上皮内部肺肿瘤免役方法医学论述，其方法小上皮内部非小上皮内部肺肿瘤（SCLC）也已才能得到法国FDA弃儿药资本评估。
复宏汉霖（2696.HK）就是一家亚太性化的自主经营转型升级海洋生物学技术医药的APP，强院于为亚洲地区患有可以提供可压力的高品格海洋生物学技术药，品牌扩大癌肿、内在免疫抗体消化道发病、皮肤科消化道发病等这个领域，已在我国的退市5款品牌，在亚太性退市1款品牌，13项不适应症应用，7个退市注测申请表拥有我国的医疗耗材监督管理系统局核发。自2030年筹建到现在，复宏汉霖已完成一身机化海洋生物学技术医药的APP，极有效率率及自主经营转型升级的自主经营重点特性贯彻新产品研发、分娩及商家运营人员全加工业链。的APP已建设改善极有效率率的亚洲地区自主经营转型升级管理系统中心，明确亚太性医疗耗材分娩水平管理系统要求（GMP）标准的展开分娩和水平严格监督，不断的筑牢一身机化宗合分娩的APP，各举，深圳徐汇基础已拥有我国的和欧洲经济共同体GMP申请审核，松江基础（一）也已拥有我国的GMP申请审核。
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，其鳞状非小细胞肺癌、广泛期小细胞肺癌和食管鳞状细胞癌3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。
ASTRUM-005: The first immunotherapy clinical study of SCLC published in JAMA, one of the top medical journals in the world
Shanghai, China, September 27th, 2022 – Shanghai Henlius Biotech, Inc. (2696.HK) announced that ASTRUM-005, an international multi-centre study led by Professor Ying Cheng, has been 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. ASTRUM-005 trial is a phase 3 study of HANSIZHUANG (serplulimab), an anti-PD-1 monoclonal antibody (mAb) developed by Henlius independently, plus chemotherapy as first-line treatment for patients with extensive-stage small cell lung cancer (ES-SCLC). After Prof. Ying Cheng orally presented them at the 2022 ASCO annual meeting, the results of ASTRUM-005 attract wide attention among the global research community. And now, ASTRUM-005 makes its way to the international arena once again, demonstrating the high level of academic acclaim on a global scale, the intelligence of Chinese researchers, and the strength of Chinese pharmaceuticals in terms of independent innovation research and clinical development.
Prof. Ying Cheng, the corresponding author and first author, as well as the leading principal investigator of the study, from Jilin Cancer Hospital, said, “In the ASTRUM-005 trial, serplulimab combined with chemotherapy achieved by far the longest OS in first-line immunotherapy for ES-SCLC. Compared with chemotherapy, the treatment prolonged median OS by 4.5 months and had the lowest HR of 0.63. In addition, the study showed good safety and consistent efficacy over time. ASTRUM-005 is the first study to demonstrate that PD-1 inhibitors plus chemotherapy can improve survival for patients with ES-SCLC. It is also the first international multi-centre phase 3 clinical study led by Chinese researchers to employ immunotherapy for ES-SCLC treatment, showcasing the expertise and excellence of Chinese researchers. I would like to thank all patients and their families, as well as researchers who contributed to this study. It opens a new chapter in first-line ES-SCLC immunotherapy, which will benefit a large number of patients."
OS 15.4 months, a new record
SCLC is the most aggressive subtype of lung cancer, accounting for around 15% of all lung cancer cases. Both limited stage SCLC (LS-SCLC) and ES-SCLC exhibit high malignancy, strong invasiveness, early metastasis, fast disease progression, and a poor prognosis. The advent of immune checkpoint inhibitors has brought new hope to patients with ES-SCLC. At present, anti-PD-L1 mAbs combined with chemotherapy have been recommended by clinical practice guidelines at home and abroad as the first-line treatment for ES-SCLC. Compared with chemotherapy, the overall survival (OS) of patients with SCLC has been prolonged to a certain extent, but the improvements were still modest, suggesting the need for more effective treatments in this patient population.
ASTRUM-005 is a randomised, double-blind, international, multi-centre, phase 3 clinical study that aims to compare the efficacy and safety of HANSIZHUANG with placebo when combined with chemotherapy in previously untreated patients with ES-SCLC. ASTRUM-005 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. As of data cutoff for this interim analysis (October 22, 2021), 585 eligible patients were randomised (serplulimab group, n=389; placebo group, n=196), with a median follow-up duration of 12.3 months. Median OS was significantly longer in the serplulimab group (15.4 months, 95% confidence interval [CI] 13.3-not evaluable) than in the placebo group (10.9 months, 95% CI 10.0-14.3) (hazard ratio [HR] 0.63, 95% CI 0.49-0.82; P <0.001). The 24-month OS rate in the two treatment groups were 43.1% and 7.9%, respectively. Median progression-free survival assessed by an independent radiology review committee per RECIST v1.1 was also longer in the serplulimab group compared to the placebo group (5.7 months vs. 4.3 months; HR 0.48, 95% CI 0.38-0.59). Incidence of immune-related adverse events (irAEs) was similar to the approved PD-1/PD-L1 antibodies.
Providing more treatment options for patients worldwide
The success of ASTRUM-005 is a breakthrough in the treatment of ES-SCLC with PD-1 inhibitors. Based on the results of ASTRUM-005, 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). Furthermore, HANSIZHUANG has been recommended for the first-line treatment of ES-SCLC by the 2022 CSCO Guidelines for Diagnosis and Treatment of SCLC.
In April 2022, the US Food and Drug Administration (FDA) has granted Orphan-Drug Designation (ODD) for HANSIZHUANG for the treatment of SCLC. Based on the positive feedback from FDA Biologics License Application (BLA) submission for HANSIZHUANG for the treatment of ES-SCLC and the discussion on the FDA's Type C consultation meeting, Henlius is planning to soon carry out a bridging study in the US and expected to submit BLA to FDA before Q1 of 2024. 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.
Looking forward, Henlius will actively improving efficiency through innovations, focusing on unmet medical needs to bring more high-quality and affordable therapies to patients worldwide.
JAMA, published continuously since 1883, is an international peer-reviewed general medical journal aiming to promote the science and art of medicine and the betterment of the public health. JAMA (impact factor of 157.3, one of the highest in medicine and science) is the most widely circulated general medical journal in the world, with more than 290,000 recipients of the print journal, more than 1.6 million recipients of electronic tables of contents and alerts, and over 38 million annual visits to the journal's website. JAMA's reach includes a growing social media presence and vast international news media exposure.
HANSIZHUANG (recombinant humanised anti-PD-1 monoclonal antibody injection, generic name: serplulimab injection) is the first innovative monoclonal antibody developed by Henlius. Up to date, 1 indication is approved for marketing in China, 3 NDAs have been accepted by the NMPA, and 11 clinical trials are ongoing across the world.
HANSIZHUANG was approved by the NMPA for the treatment of MSI-H solid tumours in March 2022 and its synergy with in-house products of the company and innovative therapies are being actively promoted. 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, the company has enrolled more than 3,100 subjects in China, Turkey, Poland, Georgia and other countries and regions, and the proportion of White is over 30% in two MRCTs, making HANSIZHUANG an anti-PD-1 mAb with one of the largest global clinical data pools. The NDAs of the first-line treatment for squamous non-small cell lung cancer (sqNSCLC), extensive-stage small cell lung cancer (ES-SCLC), and esophageal squamous cell carcinoma (ESCC) have been accepted by the NMPA, which makes HANSIZHUANG potentially the world’s first anti-PD-1 mAb for the first-line treatment of SCLC. Furthermore, HANSIZHUANG was recommended by the 2022 CSCO Guidelines for Diagnosis and Treatment of Small Cell Lung Cancer (SCLC) for the treatment of ES-SCLC, and the related clinical trial has also become the first study published in JAMA on SCLC immunotherapy. Serplulimab was also granted orphan drug designation by the FDA for treatment of SCLC.
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, 13 indications approved worldwide, and 5 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 tumors and its NDA for the treatment of squamous non-small cell lung cancer (sqNSCLC), 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.
【参考选取论文文献综述】
Cheng Y, Han L, Wu L, et al. Effect of First-Line Serplulimab vs Placebo Added to Chemotherapy on Survival in Patients With Extensive-Stage Small Cell Lung Cancer:
The ASTRUM-005 Randomized Clinical Trial.
JAMA.2022;328(12):1223–1232. doi:10.1001/jama.2022.16464
