明年九月份27日，由程颖教援领导小组的新国际多中探讨——ASTRUM-005探讨在环球八大世界级药学期刊报刊内容之五的《欧美药学会报刊内容》（JAMA，干扰系数：157.3）手机在线发过，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。
网络通信小说原作者与一、小说原作者、ASTRUM-005研发关键研发者、辽源市省良性肿瘤醫院程颖教学显示：
ASTRUM-005探索中斯鲁利单抗联和手术提升了近些年非常常见期小内部肝癌抗体力性专业的调理中最远的OS报告单，与手术对比是可以加长4.7个月的野外生存模式，目前即可即可至少的HR：0.63，并且最进治辽效果和远期治辽效果的报告单一模一样，时候有着正常的安全防护性。这方面探索第一次印证了PD-1可抑药物联和手术一模一样能解决非常常见期小内部肝癌的野外生存模式，这也是我来们中探索者加强组织领导的率先争对ES-SCLC转变症抗体力性调理的国际性多中心局临床进行治疗Ⅲ期探索，完全尽显了中探索者的整体实力。非常感谢的话整个在该探索中设计业绩的的人及子女的能默契配合，也非常感谢的话另一个探索者的付出的爱，这方面探索为非常常见期小内部肝癌专业的抗体力性调理实现了新的一张纸，为许多的人带去福利。
OS达15.4个月，刷新一线小细胞肺癌总生存期纪录
小人体组织细胞1.肺肿瘤（SCLC）约占1.肺肿瘤统计数的15%，是1.肺肿瘤中肉瘤样癌性史上最强的亚型，构成限制期小人体组织细胞1.肺肿瘤（LS-SCLC）和ES-SCLC。相对性真理互相点是恶变因素高、转入早、常见疾病进步在短时间，基本继发性不正常。近年来，抗体检验点减弱剂的冒出为ES-SCLC前沿技术的诊治提供新但愿，抗PD-L1单抗整合肿瘤肺癌晚期化疗已被我国外全威规范安利为ES-SCLC中俄原油管道诊治细则，优于肿瘤肺癌晚期化疗一些 因素上可以解决了病患者总活期，显然可以解决因素相对性局限，仍要有更效果诊治细则。
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深入分析的完成是PD-1促使剂冶疗ES-SCLC的重大事件突破点，通过该类深入分析，一个国家药物制剂执法监督检查方法局（NMPA）已受案H药专业的冶疗ES-SCLC适用症的面市申請；《CSCO小人体癌细胞非小癌细胞肝癌诊疗规范指导意见（2022版）》也新开斯鲁利单抗整合化疗药EC方法充当ES-SCLC专业的冶疗网友推荐，为中国人ES-SCLC专业的冶疗提拱了大多的选用。既如此这般，H药用价值于冶疗SCLC于2030年4月获USA食品类药物制剂执法监督检查方法局（FDA）弃儿药执证举证。一并，通过FDA对应H药冶疗ES-SCLC审核面市申請的正在向评价及FDA C类资询会议内容的讨论会效果，公司将在USA初始化一种桥接监床研究冲击试验，并拟于202历经四年Q1前在USA审核以及的面市申請。近年来中国还没有专业的冶疗SCLC的抗PD-1单抗将建，H药有希望当上中国首支专业的冶疗SCLC的抗PD-1单抗，增强发展十年PD-1促使剂专业的冶疗小人体癌细胞非小癌细胞肝癌的监床研究乱码。
的前景，复宏汉霖将一直提升去创新，以药学实际需求服务至上导，接着提高效率地为全球最大爱美者打造大多可额外的负担、明确疗效更佳的调理预案。
JAMA是携手同行评审意见的国际上性融合性中医药学学术期刊杂志杂志论文，以力促中医药学的合理与视觉各类持续改善共同环保居多要目标值。自188四年间断性股票发行十一届三中，JAMA不谏为中医药学和合理方向最具引响力的学术期刊杂志杂志论文其中之一，阶段引响因素为157.3。JAMA也是游戏世界十大股票发行更广泛的融合性中医药学类学术期刊杂志杂志论文，彩印版稿费关注数高出29万，线上稿费关注数高出160万，学术期刊杂志杂志论文网站平台的年网络用户量高出31000万，存在强劲的社交互动电视自媒体引响力和国际上性新鲜事了电视自媒体的暴光率。
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。
2030年1月，H药确认获准于调理微遥感卫星特别不动态平衡（MSI-H）实体线瘤。着眼于H药，复宏汉霖积极向上加快推进其与有限公司同一食品的协同管理与与创新性冶疗方案的联办，争相收获全国、澳大利亚、欧盟成员国等中华及省市的监床检验的缓解药理实验检测经营许可证，在全国同样做11项肉瘤免役性联办冶疗方案监床检验的缓解药理实验检测，多涉及肝癌、食管癌、头颈鳞癌和胃溃疡等自我调节症，新一轮涉及肝癌专业的调理。截止日近些年，H药于全国、俄罗斯、意大利、格鲁吉亚等中华和省市累记入组超3100人，各举2项新国际联盟联盟多基地监床检验的缓解药理实验检测入组白人的此例少于30%，是具备新国际联盟联盟监床检验的缓解药理实验统计数据较多的抗PD-1单抗产品之一。H药联办放化疗专业的调理鳞状非小上皮細胞膜肝癌（sqNSCLC）、多期小上皮細胞膜肝癌（ES-SCLC）和食管鳞状上皮細胞膜癌（ESCC）的NDA已收获NMPA结案，H药还有机会当上全国率先专业的调理SCLC的抗PD-1单抗。前者，该药当选《2022 CSCO小上皮細胞膜肝癌会诊指导书》是 ES-SCLC调理推薦，造成ES-SCLC的新国际联盟联盟多基地监床检验的缓解药理实验探析ASTRUM-005当上全国率先进入JAMA的小上皮細胞膜肝癌免役性调理监床检验的缓解药理实验探析，其调理小上皮細胞膜肝癌（SCLC）也已收获澳大利亚FDA孤寡药机会认定书。
复宏汉霖（2696.HK）是一种家展览化的多元化菌物技术化工集团子公司，全力于为高度病患保证可的负担的高厂品水平管理工作菌物技术药，厂品遍布恶性肿瘤、本身免疫检测的疫情、眼科整形的疫情等行业领域，已在国内 香港市场销售5款厂品，在展览香港市场销售1款厂品，13项适宜症应用，1个香港市场销售子公司学生申请赚取国内 食药监局审理。自20二十年成为至今，复宏汉霖已修建内置式化菌物技术化工网上平台网站，效率高及多元化的随时升级核心理念能力素质穿梭新产品研发、产量及餐饮业运营人员全领域链。集团子公司已形成建立健全效率高的高度多元化基底，依据展览处方药产量水平管理工作管理工作规范化（GMP）规则实现产量和水平管理工作控管，不停的扎实内置式化合理产量网上平台网站，各举，杭州徐汇基底已赚取国内 和欧盟国家GMP审核，松江基底（一）也已赚取国内 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.
【参考使用专著】
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
