22年8月27日，由程颖先生主办行的知名多学校论述——ASTRUM-005论述在国内七大一流医疗刊物产品之一的《芬兰医疗会报刊内容》（JAMA，影响到因素：157.3）优酷云投稿，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。
联系我与第一个我、ASTRUM-005学习主要是学习者、四平市省癌肿青岛博士整形医院医院程颖传授指出：
ASTRUM-005探索中斯鲁利单抗联手技术放疗取得了现多期小肿瘤组织组织肝癌糖尿病糖尿病患者免疫检测性组织组织优质冶疗中较长的OS报告单，与放疗好于就可以延缓4.5-7个月的环境，现今直到最高的HR：0.63，还近两年来制疗作用和远期制疗作用的报告单高度，同一时间含有更好的平安性。这一项探索第一回得知了PD-1抑制作用剂联手技术放疗相同够改善效果多期小肿瘤组织组织肝癌糖尿病糖尿病患者的环境，这也是我来们国探索者加强组织领导的首份专门针对ES-SCLC满足症免疫检测性组织组织冶疗的国际性多重点临床学习Ⅲ期探索，有力尽显了国探索者的竟争力。谢谢某个在该探索中做好突出贡献的糖尿病糖尿病患者及子女的配合，也谢谢某个探索者的迁就，这一项探索为多期小肿瘤组织组织肝癌糖尿病糖尿病患者优质免疫检测性组织组织冶疗展平了新的一张纸，为满足糖尿病糖尿病患者带去恩点。
OS达15.4个月，刷新一线小细胞肺癌总生存期纪录
小神经癌细胞癌症（SCLC）约占癌症个数的15%，是癌症中侵蚀性性最废的亚型，分类随意性期小神经癌细胞癌症（LS-SCLC）和ES-SCLC。前两者共同体点是梭形细胞肿瘤层次高、改变早、常见疾病最新动态快，总体目标愈后不正常。近两年，免役体检点阻止剂的冒出为ES-SCLC领域行业的冶疗所带来新渴望，抗PD-L1单抗联席肿瘤化疗药已被我们国家外全威导则比较适合为ES-SCLC一专多能冶疗规划，相比较肿瘤化疗药相应层次上可以有用改善了求美者总存活期，尽管可以有用改善层次相比较较少，仍想要更有用冶疗规划。
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探析的完美是PD-1减缓剂控制ES-SCLC的严重击破，应用于这项探析，一个国家otc医疗耗材督查方法系统方法系统局（NMPA）已受案H药一丝控制ES-SCLC适合症的美成功退市报考；《CSCO小神经上皮细胞1.肺癌患者诊所白皮书（2022版）》也新增加的斯鲁利单抗联动肿瘤化疗EC情况报告算作ES-SCLC一丝控制推见，为亚洲ES-SCLC一丝控制能提供了大量的进行。既都是这样，H药用价值于控制SCLC于2030年4月获美食品饮料otc医疗耗材督查方法系统方法系统局（FDA）弃婴药基础评定。同时，应用于FDA造成H药控制ES-SCLC撤签美成功退市报考的单向反馈机制及FDA C类询问会议平板的座谈报告单，集团公司将在美启动时某项桥接临床试验药学冲击试验，并拟于202历经四年Q1前在美撤签相对应的美成功退市报考。现下亚洲并未一丝控制SCLC的抗PD-1单抗将建，H药力争作为亚洲首支一丝控制SCLC的抗PD-1单抗，添补在未来十年PD-1减缓剂一丝控制小神经上皮细胞1.肺癌患者的临床试验药学空白图片。
今后，复宏汉霖将持续保持拉动多元化，以临床上消费需求为首导，仍然高效率的地为世界上客户具备其他可损失、中药治疗作用好的中药治疗计划。
JAMA是你我评审会的國际总体性医疗杂志，以增进医疗的地理学课与文化艺术或是促进公共性卫生情况遵循要关键。自188两年维持出版社出版建国以来，JAMA不复为医疗和地理学课域最具关系力的杂志的一个，日前关系因素为157.3。JAMA也是时代上发行量范围广泛的总体性医疗类杂志，进行印刷版稿费数少于29万，网上稿费数少于160万，杂志网的年远程浏览量少于3捌佰，更具更强的社交货广播校园媒体关系力和國际新闻报道广播校园媒体的曝光过度率。
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药开始获准应用于做微北斗卫星髙度不稳定可靠（MSI-H）小平面瘤。着力H药，复宏汉霖良好助推其与集团的的产品的协同管理已经与创新发展手术疗法方案的合力，接连得到华人、新西兰、欧洲经济共同体等地方及省市的药学试验上医学药学测试准许，在国.际排名搜集做11项肺部肿瘤免疫抗体性合力手术疗法方案药学试验上医学药学测试，范围广包含肺肿瘤、食管癌、头颈鳞癌和胃溃疡等适应能力症，详细包含肺肿瘤优质做。截止现今现今，H药在华人、俄罗斯、匈牙利、格鲁吉亚等地方和省市累会计入组超3100人，这之中2项国.际英文上多机构药学试验上医学药学测试入组白人的比倒大于30%，是占有国.际英文上药学试验上医学药学数剧较多的抗PD-1单抗其中之一。H药合力化疗药优质做鳞状非小神经体受损癌生殖受损细胞肺肿瘤（sqNSCLC）、范围广期小神经体受损癌生殖受损细胞肺肿瘤（ES-SCLC）和食管鳞状神经体受损癌生殖受损细胞癌（ESCC）的NDA已得到NMPA业务办理，H药可能变为国.际排名首只优质做SCLC的抗PD-1单抗。凡此种种，该药评为《2022 CSCO小神经体受损癌生殖受损细胞肺肿瘤口腔诊疗白皮书》做为ES-SCLC做建议，重视ES-SCLC的国.际英文上多机构药学试验上医学药学探讨ASTRUM-005变为国.际排名首只抵达JAMA的小神经体受损癌生殖受损细胞肺肿瘤免疫抗体性做药学试验上医学药学探讨，其做小神经体受损癌生殖受损细胞肺肿瘤（SCLC）也已得到新西兰FDA遗孤药员证认准。
复宏汉霖（2696.HK）一家时代高端化的自主化反复创新性动物学化工集团的，着力推进于为世界上排名求美者带来了可额外负担的高高的品质动物学药，成品涉及肉瘤、自身业务免役病毒、护眼病毒等区域，已在我国国内有发行5款成品，在时代国.际发行1款成品，13项适宜症应用，9个发行注册的报名赢得中华有国家药监局局核发。自2015年筹建之后，复宏汉霖已俊工整体化动物学化工渠道，效率高率的及自主化反复创新性的自主化核心内容工作能力影响制造研发、制造及商用运维全工业链。集团的已组建成熟的效率高率的的世界上排名自主化反复创新性中心局，安装时代国.际医药制造的品质工作正规（GMP）基准去制造和的品质监督控制，反复狠抓整体化综合管理制造渠道，表中，杭州徐汇军事工厂已赢得中华有和欧盟国家GMP资质企业认证，松江军事工厂（一）也已赢得中华有GMP资质企业认证。
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.
【考生医学文献】
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
