2023年5月26日，复宏汉霖（2696.HK）宣布，公司首个创新型单抗H药 汉斯状®（斯鲁利单抗）针对一线食管鳞癌（ESCC）的III期临床研究（ASTRUM-007）结果入选ASCO年会，数据更新以线上摘要的形式于ASCO官网进行展示。该研究由国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院黄镜教授牵头开展。 食管癌是全球常见的恶性肿瘤之一，最新统计数据显示，中国食管癌发病率和死亡率分别位列恶性肿瘤的第六和第五位，其中以ESCC最为常见，约占所有食管癌病例的85.79%[1]。多项研究表明抗PD-1单抗联合化疗可为食管癌患者带来生存获益，免疫检查点抑制剂联合化疗已成为我国食管癌的一线治疗标准[2]。复宏汉霖就这一适应症开展的ASTRUM-007临床试验结果曾分别于2022年CSCO年会、ESMO Asia年会上发布，此次ASCO年会上公布的该研究更新数据结果如下： 斯鲁利单抗对比安慰剂联合化疗一线治疗PD-L1阳性食管鳞状细胞癌的数据更新：一项随机双盲多中心III期研究（ASTRUM-007）（摘要编号e16016） 2019年6月19日至2021年12月17日，试验共筛选976例患者，其中551例随机分组至斯鲁利单抗联合化疗组（n=368）和化疗组（n=183）。至本次更新分析时，中位随访时间为24.2个月。斯鲁利单抗联合化疗组的中位OS显著长于化疗组（14.6 vs 11.2个月；风险比0.70，95% CI 0.57–0.86；P=0.0006）。斯鲁利单抗的加入延长了IRRC根据RECIST v1.1评估的中位PFS（6.5 vs 5.3个月；风险比0.58，95% CI 0.47–0.72）。在IRRC根据RECIST v1.1评估的确认的客观缓解率（58.7% vs 42.1%）和持续缓解时间（中位数：7.1 vs 4.6个月）上也观察到了疗效改进。 两组分别有203（53.1%）和82（48.8%）例患者报告了三级及以上治疗期间出现的不良事件（TEAE）。斯鲁利单抗联合化疗组和化疗组报告的三级及以上免疫相关不良事件的发生率分别为9.2%和3.0%。 随访增加9.3个月后，斯鲁利单抗联合化疗一线治疗PD-L1阳性晚期ESCC仍维持着良好的疗效和安全性，进一步支持开发斯鲁利单抗联合5-FU和顺铂治疗一线ESCC患者。 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），是全球首个获批一线治疗小细胞肺癌的抗PD-1单抗，目前已有3项适应症获批上市，2项适应症上市申请分别在中国和欧盟获受理，10余项临床试验同步在全球开展。 2022年3月，H药正式获批上市，目前可用于治疗微卫星高度不稳定（MSI-H）实体瘤、鳞状非小细胞肺癌（sqNSCLC）及广泛期小细胞肺癌（ES-SCLC）。H药联合化疗一线治疗食管鳞状细胞癌（ESCC）和一线治疗广泛期小细胞肺癌（ES-SCLC）的上市申请也分别获得中国NMPA和欧盟EMA受理。聚焦肺癌和消化道肿瘤，复宏汉霖积极推进H药与公司其他产品的协同以及与创新疗法的联合，相继获得中国、美国、欧盟等国家及地区的临床试验许可，在全球同步开展14项肿瘤免疫联合疗法临床试验。截至目前，H药已于中国、美国、土耳其、波兰、格鲁吉亚等国家和地区累计入组超3500人，其中2项国际多中心临床试验入组白人的比例超过30%，是拥有国际临床数据较多的抗PD-1单抗之一。H药多项关键性临床研究结果分别发表于知名期刊《美国医学会杂志》（JAMA，影响因子：157.3）、《自然-医学》（Nature Medicine，影响因子：87.241）、British Journal of Cancer（影响因子：9.075）和Frontiers in Immunology（影响因子：8.786）。此外，H药还荣获《CSCO 小细胞肺癌诊疗指南》、《CSCO非小细胞肺癌诊疗指南》、《CSCO 食管癌诊疗指南》、《CSCO结直肠癌诊疗指南》、《CSCO免疫检查点抑制剂临床应用指南》和《中国食管癌放射治疗指南》等多部权威指南推荐，为肿瘤临床诊疗提供重要参考。海外方面，H药治疗SCLC也已获得美国FDA和欧盟EC的孤儿药资格认定，并在美国启动了一项H药对比一线标准治疗阿替利珠单抗的头对头桥接试验。 关于复宏汉霖 复宏汉霖（2696.HK）是一家国际化的创新生物制药公司，致力于为全球患者提供可负担的高品质生物药，产品覆盖肿瘤、自身免疫疾病、眼科疾病等领域，已在中国上市5款产品，在国际上市1款产品，18项适应症获批，3个上市申请分别获中国药监局、美国FDA和欧盟EMA受理。自2010年成立以来，复宏汉霖已建成一体化生物制药平台，高效及创新的自主核心能力贯穿研发、生产及商业运营全产业链。公司已建立完善高效的全球创新中心，按照国际药品生产质量管理规范（GMP）标准进行生产和质量管控，不断夯实一体化综合生产平台，其中，上海徐汇基地已获得中国和欧盟GMP认证，松江基地（一）也已获得中国GMP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、鳞状非小细胞肺癌和广泛期小细胞肺癌，成为全球首个获批一线治疗小细胞肺癌的抗PD-1单抗，其食管鳞状细胞癌适应症的上市注册申请也正在审评中。公司亦同步就16个产品在全球范围内开展30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。 Results from the Phase 3 Clinical Study of Novel Anti-PD-1 mAb Serplulimab for the First-line Treatment of ESCC Released at 2023 ASCO Annual Meeting Shanghai, China, May 26th, 2023 –Shanghai Henlius Biotech, Inc. (2696.HK) announced that the updated results of the phase 3 clinical study (ASTRUM-007) of company’s self-developed innovative anti-PD-1 mAb, HANSIZHUANG (serplulimab), targeting the first-line treatment of esophageal squamous cell carcinoma (ESCC), were released as online abstract by 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. ASTRUM-007 was led by Professor Jing Huang from National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Esophageal cancer is one of the most common malignancies in the world. According to the latest data, the incidence and mortality of esophageal cancer rank sixth and fifth, respectively, among all malignant tumors in China, of which ESCC accounts for about 85.79% of all esophageal cancer cases[1]. Many studies have shown that anti-PD-1 mAb combined with chemotherapy can bring survival benefits to patients with esophageal cancer. Immune checkpoint inhibitor combined with chemotherapy has become the standard first-line treatment for advanced esophageal cancer in China[2]. The results of ASTRUM-007, a clinical trial conducted by Henlius for ESCC, have been presented at the 2022 CSCO Annual Meeting and ESMO Asia Congress 2022. Its updated data released at 2023 ASCO Annual Meeting are as follows: Title Updated results of first-line serplulimab versus placebo plus chemotherapy in PD-L1–positive esophageal squamous cell carcinoma: A randomized, double-blind, multicenter phase 3 study (ASTRUM-007) (Abstract No. e16016) Study design In this randomized, double-blind, multicenter phase 3 study, patients with histologically confirmed locally advanced or distantly metastatic, PD-L1–positive (CPS ≥1) esophageal squamous cell carcinoma (ESCC) who had no prior systemic antitumor therapy were randomized 2:1 to receive serplulimab 3 mg/kg or placebo plus chemotherapy (5-FU + cisplatin) intravenously Q2W. Randomization was stratified by PD-L1 expression level (CPS ≥10 vs CPS <10), age (≥65 vs <65 years), and disease status (locally advanced vs distantly metastatic). The primary endpoints were IRRC-assessed progression-free survival (PFS) per RECIST v1.1 and OS. Secondary endpoints included other efficacy measures, safety, quality of life, and biomarkers. Results Between June 19, 2019 and December 17, 2021, 976 patients were screened and 551 were randomized (serplulimab-chemotherapy, n=368; placebo-chemotherapy, n=183). At this updated analysis, median follow-up duration was 24.2 months. Median OS was significantly longer in the serplulimab-chemotherapy group than the placebo-chemotherapy group (14.6 vs 11.2 months; hazard ratio [HR] 0.70, 95% CI 0.57–0.86; P=0.0006). IRRC-assessed median PFS per RECIST v1.1 was prolonged with the addition of serplulimab (6.5 vs 5.3 months; HR 0.58, 95% CI 0.47–0.72). Efficacy improvements were also observed in confirmed objective response rate (58.7% vs 42.1%) and duration of response (median, 7.1 vs 4.6 months) as assessed by IRRC per RECIST v1.1. Grade ≥3 treatment-related adverse events were reported in 203 (53.1%) and 82 (48.8%) patients in the respective groups. Incidence of grade ≥3 immune-related adverse events were 9.2% and 3.0% in the serplulimab-chemotherapy group and the placebo-chemotherapy group, respectively. Conclusion With another 9.3 months of follow-up, the encouraging efficacy and manageable safety of serplulimab plus chemotherapy as first-line treatment in patients with PD-L1–positive advanced ESCC were maintained, further supporting the development of serplulimab plus 5-FU and cisplatin for previously untreated ESCC patients. 【参考文献】 [1] Chen R, Zheng R, Zhang S, et al. Patterns and trends in esophageal cancer incidence and mortality in China: an analysis based on cancer registry data[J]. Journal of the National Cancer Center, 2023. [2] 食管癌诊疗指南（2022年版）. 中国国家卫生健康委员会. About HANSIZHUANG HANSIZHUANG (recombinant humanized anti-PD-1 monoclonal antibody injection, generic name: serplulimab injection) is the first anti-PD-1 mAb for the first-line treatment of SCLC. Up to date, 3 indications are approved for marketing in China, 2 marketing applications are under review in China and the EU, and more than 10 clinical trials are ongoing across the world. HANSIZHUANG was launched in March 2022 and has been approved by the NMPA for the treatment of MSI-H solid tumours, squamous non-small cell lung cancer (sqNSCLC) and extensive-stage small cell lung cancer (ES-SCLC). The marketing applications of the first-line treatment for esophageal squamous cell carcinoma (ESCC) and ES-SCLC are under review by the NMPA and the EMA, respectively. Focus on lung and gastrointestinal cancer, the synergy of HANSIZHUANG 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 14 clinical trials on immuno-oncology combination therapies in a wide variety of indications. As of now, the company has enrolled more than 3,500 subjects in China, the U.S., 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 results of pivotal trials of HANSIZHUANG were published in the Journal of the American Medical Association (JAMA, IF: 157.3), Nature Medicine (IF: 87.241), the British Journal of Cancer (IF: 9.075) and Frontiers in Immunology（IF：8.786）, respectively. On the other hand, HANSIZHUANG was recommended by the CSCO Guidelines for Small Cell Lung Cancer, the CSCO Guidelines for Non-Small Cell Lung Cancer, the CSCO Guidelines for Esophageal Cancer, the CSCO Guidelines for Colorectal Cancer, the CSCO Clinical Practice Guidelines on Immune Checkpoint Inhibitor, the China Guidelines for Radiotherapy of Esophageal Cancer and other definitive guides, providing valuable references for clinical diagnosis and treatment of tumours. Furthermore, serplulimab was granted orphan drug designations by the FDA and the EC for the treatment of SCLC, and the first patient has been dosed in a bridging head-to-head trial in the United States to comparing HANSIZHUANG to standard of care atezolizumab (anti-PD-L1 mAb) for the first-line treatment of ES-SCLC. About Henlius 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 has been approved for marketing in overseas markets, 18 indications are approved worldwide, and 3 marketing applications have been accepted for review in China, the U.S., and the EU, respectively. 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 for injection, 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, squamous non-small cell lung cancer (sqNSCLC) and extensive-stage small cell lung cancer (ES-SCLC), making it the world’s first anti-PD-1 mAb for the first-line treatment of SCLC. Its NDA for the treatment of esophageal squamous cell carcinoma (ESCC) is under review. What's more, Henlius has conducted over 30 clinical studies for 16 products, expanding its presence in major markets as well as emerging markets. 联系方式 媒体：PR@Henlius.com 投资者：IR@Henlius.com论文题目
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