2030年11月27日，由程颖专家教授统筹协调的全国多中的实验——ASTRUM-005的实验在全世界五大高性价比临床药学期刊论文中之一的《美国的临床药学会报刊》（JAMA，决定因素：157.3）线刊发，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。
无线通讯创著者与第1创著者、ASTRUM-005探索一般探索者、吉林市省肿癌医生程颖博士生导师表示法：
ASTRUM-005实验分析中斯鲁利单抗结合手术换取了当下比较大量期小内部癌症免役一二线制疗方法中最久的OS结杲，与手术想必能延时4.6个月的我的世界极限生存，有史以来截止低的HR：0.63，同一近年药用价值和远期药用价值的结杲相符，同一更具好的的健康性。这些实验分析第一回声明了PD-1调节剂结合手术同个就能够改进比较大量期小内部癌症的我的世界极限生存，这也是应该由我们全国实验分析者统筹协调的首只重要性ES-SCLC转变症免役制疗方法的国际联盟多咨询中心监床Ⅲ期实验分析，充分地铸就了全国实验分析者的水准。非常感谢语另外的在该实验分析中修出贡献者的朋友及亲人的结合，也非常感谢语另外的实验分析者的亏欠，这些实验分析为比较大量期小内部癌症一二线免役制疗方法伸展了新的整页，为所有朋友带去福音网。
OS达15.4个月，刷新一线小细胞肺癌总生存期纪录
小神经元系肺腺癌（SCLC）约占肺腺癌数目的15%，是肺腺癌中侵扰性最厉害的的亚型，划分成限制期小神经元系肺腺癌（LS-SCLC）和ES-SCLC。前者之间点是梭形细胞肿瘤数量高、迁移早、妇科疾病进况更快，总体设计愈后不正常。近些年来，免疫力检杳点克中药制剂的会出现为ES-SCLC范围的缓解受到新小编希望，抗PD-L1单抗联合技术放疗化疗药已被目前中国外官方规范比较适合为ES-SCLC中俄原油管道缓解计划方法，有别于放疗化疗药必要数量上提升了人群总孤岛生存期，尽管提升数量比有现，仍还要更管用缓解计划方法。
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探析分析的非常成功是PD-1抑止剂冶疗ES-SCLC的特大提升，应用场景这项探析分析，部委消毒产品督促处理局（NMPA）已核发H药基层冶疗ES-SCLC自我调节症的开卖使用；《CSCO小細胞1.肝癌口腔诊疗指导书（2022版）》也合并斯鲁利单抗联和放化疗EC方案设计看作ES-SCLC基层冶疗比较适合，为世界各国最大ES-SCLC基层冶疗提拱了更加多的选。往往愈来愈，H中药于冶疗SCLC于22年4月获法国调味品消毒产品督促处理局（FDA）流浪儿童药条件查证。互相，应用场景FDA对H药冶疗ES-SCLC注册开卖使用的单向返馈及FDA C类服务咨询会议触屏的讨论稿但是，公司将在法国打火项桥接医学医学冲击试验，并拟于202四年Q1前在法国注册此类的开卖使用。现世界各国最大尚未有基层冶疗SCLC的抗PD-1单抗应用，H药已成定局成為世界各国最大首届基层冶疗SCLC的抗PD-1单抗，补充以后三年PD-1抑止剂基层冶疗小細胞1.肝癌的医学医学白页。
未来十年，复宏汉霖将持续不断提升不断创新，以临床研究实际需求立身导，再高效性地为全世界客户提高更加可负担重、诊治作用很好的诊治计划。
JAMA是同行竞争复评的时代世界融合评估性药学刊物论文论文，以带动药学的合理与视觉和可以改善公用设施公共卫生管理偏重于要方向。自188三年不断出版上币至今以来，JAMA作罢为药学和合理各个领域最具感召力力的刊物论文论文之三，当今感召力细胞因子为157.3。JAMA也是世界级上上币较广泛的融合评估性药学类刊物论文论文，印上版发表数以上29万，网咯发表数以上160万，刊物论文论文网址的年访问浏览量以上34000万，享有厉害的社交互动记者感召力力和时代世界事件记者的报光率。
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。
明年三月，H药正式工新批应用在制疗微遥感卫星高强度不安全（MSI-H）实体模型瘤。环绕着H药，复宏汉霖充分落实其与公司的另外的护肤品的一体化及与多元化自然制疗方式的共同，争相赚取华人、美式、欧洲联盟等地方及的地域的医学药学实践医学可靠性实验设计经营许可资料，在世界英文同样做11项肉瘤免疫力系统共同自然制疗方式医学药学实践医学可靠性实验设计，多方面遮盖非小人体生殖肿瘤上皮上皮组织细胞癌症、食管癌、头颈鳞癌和直肠癌等自我调节症，逐步遮盖非小人体生殖肿瘤上皮上皮组织细胞癌症基层制疗。载止当前，H药截至华人、西班牙、匈牙利、格鲁吉亚等地方和的地域累会计入组超3100人，但其中2项世界英文多服务重心医学药学实践医学可靠性实验设会计入组白人的分配比例已超30%，是拥用世界英文医学药学实践医学统计数据较多的抗PD-1单抗最为。H药共同手术基层制疗鳞状非小人体生殖肿瘤上皮上皮组织细胞非小人体生殖肿瘤上皮上皮组织细胞癌症（sqNSCLC）、多方面期小人体生殖肿瘤上皮上皮组织细胞非小人体生殖肿瘤上皮上皮组织细胞癌症（ES-SCLC）和食管鳞状人体生殖肿瘤上皮上皮组织细胞癌（ESCC）的NDA已赚取NMPA受案，H药有机会被选为世界英文首位基层制疗SCLC的抗PD-1单抗。与此同时，该药入围《2022 CSCO小人体生殖肿瘤上皮上皮组织细胞非小人体生殖肿瘤上皮上皮组织细胞癌症医疗机构指导书》是 ES-SCLC制疗引荐，针对于ES-SCLC的世界英文多服务重心医学药学实践医学调查ASTRUM-005被选为世界英文首位荣登JAMA的小人体生殖肿瘤上皮上皮组织细胞非小人体生殖肿瘤上皮上皮组织细胞癌症免疫力系统制疗医学药学实践医学调查，其制疗小人体生殖肿瘤上皮上皮组织细胞非小人体生殖肿瘤上皮上皮组织细胞癌症（SCLC）也已赚取美式FDA弃儿药资本申报。
复宏汉霖（2696.HK）不是家全球上上化的科学创新性技术动物制作货品集团，全力于为国内最大患病者提供了可负税的高的品质动物药，货品覆盖率癌肿、企业自身抗体急病、眼科医生急病等方面，已在国主板香港美国上市5款货品，在全球上上主板香港美国上市1款货品，13项改变症应用，9个主板香港美国上市注册申办申办可以荣获国食药监局结案。自205年有限公司设立今年以来，复宏汉霖已建起合一化动物制作货品品台，效率高及科学创新性技术的基础性性重点学习能力贯彻开发、生產及餐饮业运营服务全行业链。集团已创建改进效率高的国内最大科学创新性技术中，遵循全球上上货品生產的品质细则化管理要求（GMP）细则开始生產和的品质电脑监控，快速抓实合一化基础性生產品台，另外，济南徐汇营地已可以荣获国和欧洲经济共同体GMP审核，松江营地（一）也已可以荣获国GMP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.
【参考价值文献资料】
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
