2020年3月27日，由程颖专家统筹协调的国际级多中心站探讨——ASTRUM-005探讨在亚洲地区八大超一流临床学术期刊最为的《美利坚共和国临床会杂物》（JAMA，关系细胞：157.3）线上投稿，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。
通信技术作著与第一点作著、ASTRUM-005分析首要分析者、白山市省良性肿瘤医院专家程颖讲师指出：
ASTRUM-005学习中斯鲁利单抗共同放疗刷快了现今广期小神经元膜非小神经元肺癌女性提高天然免疫抗体神经元基层医疗中最大的OS但是，与放疗想必就可以增加4.5-7个月的繁衍，到目前已经已经低的HR：0.63，另外这段时间成效和远期成效的但是不对，一并具比较好的应急性。此项学习第一时间得知了PD-1就可以抑注射剂共同放疗都就可以缓和广期小神经元膜非小神经元肺癌女性提高的繁衍，这也是应该由我们中学习者领头的正式启动重要性ES-SCLC顺应症天然免疫抗体神经元医疗的国际英文多机构监床Ⅲ期学习，完全体现了中学习者的知名度。道谢大多数在该学习中产生影响力的提高及子女的协调一致，也道谢另一学习者的投入，此项学习为广期小神经元膜非小神经元肺癌女性提高基层天然免疫抗体神经元医疗刺激性了新的一张纸，为满足提高带去好消息。
OS达15.4个月，刷新一线小细胞肺癌总生存期纪录
小神经细胞核非小细胞核肺腺癌（SCLC）约占非小细胞核肺腺癌个数的15%，是非小细胞核肺腺癌中侵蚀性性中国最强的亚型，划分成的局限期小神经细胞核非小细胞核肺腺癌（LS-SCLC）和ES-SCLC。两者之间点是恶意数量较高、变更早、妇科疾病新进展快速发展，环境承载力疗效不合格品。近几年，免疫细胞观察点减缓剂的存在为ES-SCLC行业领域的改变带去新盼望，抗PD-L1单抗聯合放疗药已被国产外是权威性的指引个性化推荐为ES-SCLC一专多能改变方法，对放疗药千万数量较上改变了客户总存在期，但改变数量较对限制，仍须要更效果改变方法。
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钻研的成功的英文是PD-1阻止剂进行调理ES-SCLC的特大击破，依托于该类钻研，发展中国有家放射性处方药质量质量监督的标准化管理处官方网站（NMPA）已业务办理H处方药牌进行调理ES-SCLC适应性症的挂牌出现申办；《CSCO小受损组织肺肿瘤患者医疗指引（2022版）》也将新增斯鲁利单抗联和手术EC计划书有所作为ES-SCLC品牌进行调理高性价比，为中国有ES-SCLC品牌进行调理可以提供了多的决定。除了这么，H中药于进行调理SCLC于22年4月获俄罗斯食物放射性处方药质量质量监督的标准化管理处官方网站（FDA）遗孤药能力介定。还，依托于FDA针对性H药进行调理ES-SCLC呈交挂牌出现申办的正在向意见反馈及FDA C类咨讯会议触屏的谈论结局，单位将在俄罗斯再启动一个桥接临床药理上经过多次实验发现，并拟于2021年Q1前在俄罗斯呈交某些的挂牌出现申办。现阶段各国还没有品牌进行调理SCLC的抗PD-1单抗将建，H药可能拥有各国首位品牌进行调理SCLC的抗PD-1单抗，弥补明天三年期PD-1阻止剂品牌进行调理小受损组织肺肿瘤患者的临床药理上空缺。
未来生活，复宏汉霖将持续保持加仓的创新，以临床实验要为首导，继读高效化地为世界十大女性带来较多可额外负担、诊疗效果好些的诊疗规划。
JAMA是竞争对手评定的香港國际综上性分子生物学论文刊物杂志，以可以淡化分子生物学的专业与的艺术相应促进通用环卫应以要目标值。自1884年连续不断出版权十一届三中，JAMA往事不可追为分子生物学和专业行业领域最具反应力的论文刊物杂志最为，当下反应细胞因子为157.3。JAMA也是世界级上发行日最广泛泛的综上性分子生物学类论文刊物杂志，纸箱印刷版读者订报数已经不超29万，在线读者订报数已经不超160万，论文刊物杂志系统的年访问就会量已经不超3八百万，具备很强的社群网络媒介反应力和香港國际事件网络媒介的拍摄率。
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12月，H药正式宣布应用适用手术治療微北斗卫星的高度不可靠（MSI-H）小平面瘤。围绕着 H药，复宏汉霖积极地促进其与我司其他好产品的融合及与全新的治療方法的合作，先后可以荣获全国、USA、欧洲共同体等国及城市的药学检验检验可靠性做实验的时候准许，在环球搜集推进11项恶性肿瘤免疫检测抗体合作的治療方法药学检验检验可靠性做实验的时候，诸多履盖肺腺癌、食管癌、头颈鳞癌和胃溃疡等认知症，全部履盖肺腺癌一专多能手术治療。截止现如今现如今，H药已经在全国、土尔其、匈牙利、格鲁吉亚等国和城市累会计入组超3100人，其中的2项时代國際多重点药学检验检验可靠性做实验的时候入组白人的占比已经超过30%，是享用时代國際药学检验检验统计数据较多的抗PD-1单抗其中之一。H药合作放疗化疗一专多能手术治療鳞状非小组织核肺腺癌（sqNSCLC）、诸多期小组织核肺腺癌（ES-SCLC）和食管鳞状组织核癌（ESCC）的NDA已可以荣获NMPA结案，H药有希望变成环球正式启动一专多能手术治療SCLC的抗PD-1单抗。不仅而且，该药参评《2022 CSCO小组织核肺腺癌的医治手册》看作ES-SCLC手术治療推建，面向ES-SCLC的时代國際多重点药学检验检验探讨ASTRUM-005变成环球正式启动重登JAMA的小组织核肺腺癌免疫检测抗体手术治療药学检验检验探讨，其手术治療小组织核肺腺癌（SCLC）也已可以荣获USAFDA弃婴药申请资格申报。
复宏汉霖（2696.HK）不是家国家化的全新动物药业有限厂家厂家，努力于为亚洲病员作为可额外的负担的高品性动物药，车辆设备设备覆盖率肉瘤、自我免疫细胞消化道疾患、骨科消化道疾患等范围，已在我国什么时候推出5款车辆设备设备，在国家什么时候推出1款车辆设备设备，13项适合症获准，4个什么时候推出注册注册换取我国非处方药监督管理方法局授理。自20五年创立起来，复宏汉霖已开工建设内置式化动物药业有限厂家手机平台网站，有效及全新的自行核心区效果影响研发项目管理方法、生育方式及服务业运营的全加工业链。厂家已成立全面有效的亚洲全新主，遵循国家非处方药生育方式质理管理方法管理方法要求（GMP）规定来生育方式和质理管理方法安全控制，不断的增强内置式化融合生育方式手机平台网站，进来，东莞徐汇军事集散地已换取我国和欧盟国家GMP实名身份验证，松江军事集散地（一）也已换取我国GMP实名身份验证。
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，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.
【对比文献综述】
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
