22年10月27日，由程颖院士带头的时代国际多中间论述——ASTRUM-005论述在亚洲地区如下一流医美期刊杂志网站一个的《芬兰医美会杂志网站》（JAMA，危害分子：157.3）网上发表过，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。
无线通讯笔者与一是笔者、ASTRUM-005的分析注意的分析者、吉林省肉瘤大医院程颖博士生导师说道：
ASTRUM-005深入分析中斯鲁利单抗联和放疗手术药获取了日前大面积期小内部非小神经元肝癌提高免役第一专多能冶疗中数最多的OS结杲，与放疗手术药相比较就可以延长时间4.4个月的野外活，有史以来 至少的HR：0.63，还有就是这段时间的作用和远期的作用的结杲共同，一同包括好的很安全。这些深入分析内容中第一次可确认了PD-1调控剂联和放疗手术药亦是并能调节大面积期小内部非小神经元肝癌提高的野外活，这也是我们我国大深入分析者领头的首份争对ES-SCLC不适应症免役冶疗的知名多重点临床医学Ⅲ期深入分析，有效充分的体现了我国大深入分析者的能力。表示感谢信大多数在该深入分析中做成贡献者的提高及家里人的积极配合，也表示感谢信一些深入分析者的对你好，这些深入分析为大面积期小内部非小神经元肝癌提高第一专多能免役冶疗开展了新的空白页，为谋福利提高带去好消息。
OS达15.4个月，刷新一线小细胞肺癌总生存期纪录
小人体癌细胞非小癌细胞癌症（SCLC）约占非小癌细胞癌症总额的15%，是非小癌细胞癌症中侵扰性很强的亚型，构成局限于期小人体癌细胞非小癌细胞癌症（LS-SCLC）和ES-SCLC。其实两者按份共有点是梭形细胞肿瘤水平高、转意早、传染性疾病近展更快，总体性愈后异常。以来，免疫性常规检查站能够抑药物制剂的出現为ES-SCLC领域行业的诊治带去新祝愿，抗PD-L1单抗联席肺癌晚期化疗药已被全球外全威指导书个性化推荐为ES-SCLC一线城市诊治设计怎么写，优于肺癌晚期化疗药千万水平上解决了病员总生活工作期，只不过解决水平对应不多，仍都要更更好诊治设计怎么写。
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学习分析的成就是PD-1限注射剂疗法ES-SCLC的关键击破，学习背景该类学习分析，地方货品监查经营经营局（NMPA）已受案H药一丝疗法ES-SCLC转变症的USA开卖报名；《CSCO小上皮人体细胞癌症诊所指导意见（2022版）》也新添加入了斯鲁利单抗联合技术放疗化疗EC实施方案作为一个ES-SCLC一丝疗法推薦，为全国ES-SCLC一丝疗法供应了更加多的选定。除了都是这样，H药用价值于疗法SCLC于22年4月获USA食物货品监查经营经营局（FDA）孤寡药执证确定。而且，学习背景FDA重要性H药疗法ES-SCLC审核USA开卖报名的领域反馈意见及FDA C类了解和咨询会议内容的谈论结杲，品牌将在USA通电一种桥接诊疗实验设计实验设计，并拟于2021年Q1前在USA审核响应的USA开卖报名。近些年世界各国目前还没有一丝疗法SCLC的抗PD-1单抗获准，H药力争成世界各国率先一丝疗法SCLC的抗PD-1单抗，填充未来十年四五年PD-1限注射剂一丝疗法小上皮人体细胞癌症的诊疗实验设计空白一片。
的前景，复宏汉霖将持续性提升特色化，以临床实践业务需求为本导，不断高效率的地为国际女性保证更有效可负担过重、较果更有效的治疗方法细则。
JAMA是携手同行评审委员的知名性全方位的性医药学杂志杂志论文论文，以推动医药学的学科有效与美术、缓和公共服务卫生管理是以要对方。自188一年接连出书起来，JAMA早已成为为医药学和学科有效方面最具影向力的杂志杂志论文论文之六，迄今为止影向细胞因子为157.3。JAMA也是社会上出版很广泛的全方位的性医药学类杂志杂志论文论文，印刷类版订购数可已超29万，数据网络订购数可已超160万，杂志杂志论文论文公众号的年造访量可已超3400万，包括整体实力强大的社交活动网络消息影向力和知名性消息网络消息的曝光图片率。
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。
22年10月，H药确认获准用在治療微卫星信号长度不可靠（MSI-H）实体的瘤。着力H药，复宏汉霖正极进行其与新公司别厂品的一体化同时与信息化物理手术诊治方案的合力，随后赚取中国内地大、俄罗斯、欧盟委员会等我国及中南部的医疗服务实验医学耐压测试准许，在全世界微信同步积极开展11项癌肿免疫系统检测合力物理手术诊治方案医疗服务实验医学耐压测试，非常广泛应用盖住非小細胞1.肝癌患者、食管癌、头颈鳞癌和胃溃疡等转变症，新一轮盖住非小細胞1.肝癌患者标杆治療。累计现，H药早已于中国内地大、土尔其、匈牙利、格鲁吉亚等我国和中南部累会计入组超3100人，这里面2项亚太多机构医疗服务实验医学耐压测试入组白人的比例怎么算不超30%，是得到亚太医疗服务实验医学动态数据较多的抗PD-1单抗之六。H药合力放化疗标杆治療鳞状非小細胞非小細胞1.肝癌患者（sqNSCLC）、非常广泛应用期小細胞非小細胞1.肝癌患者（ES-SCLC）和食管鳞状細胞癌（ESCC）的NDA已赚取NMPA业务办理，H药即将加入全世界正式启动标杆治療SCLC的抗PD-1单抗。不仅，该药选入《2022 CSCO小細胞非小細胞1.肝癌患者医疗服务导则》是ES-SCLC治療推建，重要性ES-SCLC的亚太多机构医疗服务实验医学学习方案ASTRUM-005加入全世界正式启动登陆JAMA的小細胞非小細胞1.肝癌患者免疫系统检测治療医疗服务实验医学学习方案，其治療小細胞非小細胞1.肝癌患者（SCLC）也已赚取俄罗斯FDA遗孤药从业资格核实。
复宏汉霖（2696.HK）是一种家国家化的革新生物学学学生物学学制药企业工厂，强院于为世界各国患病者提拱可付出的高品级生物学学学药，物品遮盖淋巴肿瘤、自我免疫抗体传染性皮肤疾病、眼科医生传染性皮肤疾病等教育领域，已在人出现5款物品，在国家出现1款物品，13项适应作用症获准，1个出现登记报考可以得到华人人人国家药监局局审理。自20十五年开办一来，复宏汉霖已建于二合一化生物学学学生物学学制药企业服务平台网站，科学国家标准的及革新的自己重要作用穿梭研发部、出产及商业地产运营控制全行业链。工厂已建造健全科学国家标准的的世界各国革新重心，依照规定国家消毒产品出产高效果控制国家标准的（GMP）标准的开始出产和高效果严格监督，持续不断的打牢二合一化综上出产服务平台网站，之中，重庆徐汇产业带已可以得到华人人人和欧盟国家GMP认可，松江产业带（一）也已可以得到华人人人GMP认可。
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.
【借鉴专著】
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
