LZM-009(Livzon Group Livzon Pharmaceutical Factory)

2024年10月24日，复宏汉霖（2696.HK）宣布，公司自主研发的PD-1抑制剂H药 汉斯状®（斯鲁利单抗）联合贝伐珠单抗联合化疗用于一线治疗转移性结直肠癌（mCRC）患者的国际多中心III期临床研究（即II/III期国际多中心临床研究ASTRUM-015的III期阶段）完成日本首例患者给药。此前，ASTRUM-015研究已启动III期临床阶段研究并于中国和印度尼西亚完成首例受试者给药。 结直肠癌（CRC）是全球最常见的恶性肿瘤之一。据WHO数据显示，2022年全球约有超过190万新发病例，死亡病例逾90万例[1]。预计到2040年，全球CRC新发病例将增加63%，每年将有320万新发病例并导致每年超过160万患者死亡[2]。根据最新版中国癌症统计报告数据显示，中国的CRC发病率、死亡率在全部恶性肿瘤中分别位居第2和第4位，其中2022年新发病例51.7万，死亡病例24万[2]。而日本的CRC新发和死亡病例在其全部恶性肿瘤中分别位居第1和第2位，其中2022年新发病例14.6万，死亡病例6万[1]。 大部分CRC患者在诊断时已发生转移，mCRC肿瘤按照分子表型可划分为dMMR/MSI-H型和pMMR/MSS型，后者占比约95% [3,4]。目前，mCRC的标准一线治疗方案主要为血管内皮生长因子（VEGF）抑制剂（如贝伐珠单抗）联用化疗[5-7]，但持续疗效和预后仍有待进一步改善。研究表明，抗PD-1单抗可为dMMR/MSI-H晚期mCRC患者带来显著生存获益[8,9]。然而，占比更高的pMMR/MSS型mCRC肿瘤对单药免疫治疗反应率很低，被称为免疫治疗“冷肿瘤”。目前，全球尚无覆盖pMMR/MSS型mCRC患者的一线免疫疗法获批，这一患者群体存在巨大的未满足临床需求。 以临床需求为导向，复宏汉霖积极开展mCRC领域的免疫疗法探索，希望为更多mCRC患者提供更有效的治疗方法。ASTRUM-015研究是一项H药 汉斯状®（斯鲁利单抗）联合贝伐珠单抗和化疗一线治疗mCRC的II/III期临床研究，其II期阶段研究结果相继入选2024年美国临床肿瘤学会胃肠道肿瘤研讨会（ASCO GI）和2024 ASCO，并于近期发表于Cell Press细胞出版社旗下的综合性医学旗舰期刊Med，获得了国际学术界的高度认可。研究结果显示，H药联合贝伐珠单抗和化疗可改善未经治疗的mCRC患者（含MSS型mCRC患者）的无进展生存期及其他疗效指标，且安全性可控。这些结果支持斯鲁利单抗联合贝伐珠单抗和化疗作为一种非常有前景的mCRC一线治疗方案。 聚焦肺癌与消化道肿瘤，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，于全球同步开展10余项肿瘤免疫联合疗法临床试验，累计入组逾4400名受试者。未来公司将持续加速推进该研究，H药有望成为全球首个一线治疗mCRC的抗PD-1单抗，填补一线免疫治疗mCRC的临床空白。 【参考文献】 [1] Bray F, Laversanne M, Sung H, et al. CA Cancer J Clin. 2024: 1-35. [2] WHO Colorectal Cancer Fact Sheets, Available from: https://www-who-int.libproxy1.nus.edu.sg/news-room/fact-sheets/detail/colorectal-cancer, accessed [15 May 2024] [3] Diaz, L. A., Jr. et al. Lancet Oncol 23, 659-670 (2022). [4] Lenz, H. J. et al. J Clin Oncol 40, 161-170 (2022). [5] Iwasa, S. et al. Cancer Commun (Lond) 43, 519-522 (2023). [6] Hurwitz, H. et al. N Engl J Med 350, 2335-2342 (2004). [7] Benson, A. B. et al. J Natl Compr Canc Netw 20, 1139-1167 (2022) [8] Overman MJ, Kopetz S, McDermott RS, et al. Nivolumab ± ipilimumab in treatment (tx) of patients (pts) with metastatic colorectal cancer (mCRC) with and without high microsatellite instability (MSI-H): CheckMate-142 interim results (abstract). J Clin Oncol 34, 2016 (suppl; abstr 3501). [9] Overman MJ, Lonardi S, Wong KYM, et al. Durable Clinical Benefit with Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer. J Clin Oncol 2018; 36:773. 关于H药 汉斯状® 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，已在中国和多个东南亚国家获批上市。截至目前，H药已有4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药正式于中国获批上市，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）、广泛期小细胞肺癌（ES-SCLC）及食管鳞状细胞癌（ESCC）。H药联合化疗一线治疗非鳞状非小细胞肺癌（nsNSCLC）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，在全球同步开展10余项肿瘤免疫联合疗法临床试验，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4000人。H药的4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）、《自然-医学》（Nature Medicine）、Cancer Cell和British Journal of Cancer。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，已有6款产品在中国获批上市，3款产品在国际获批上市，24项适应症获批，3个上市申请分别获中国药监局和欧盟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，公司商业化生产基地已相继获得中国、欧盟和美国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50多个分子，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。截至目前，公司已获批上市产品包括国内首个生物类似药汉利康®（利妥昔单抗）、自主研发的中美欧三地获批单抗生物类似药汉曲优®（曲妥珠单抗，美国商品名：HERCESSI™，欧洲商品名：Zercepac®）、汉达远®（阿达木单抗）、汉贝泰®（贝伐珠单抗）以及汉奈佳®（奈拉替尼），此外，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、广泛期小细胞肺癌和食管鳞状细胞癌，并成为全球首个获批一线治疗小细胞肺癌的抗PD-1单抗。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。 First Patient in Japan Dosed for MRCT Phase 3 Study on First-Line mCRC of Henlius Anti-PD-1 mAb Serplulimab Shanghai, China, October 24, 2024 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first patient in Japan has been dosed in the phase 3 stage of the international multi-centre clinical trial (ASTRUM-015) of the company’s self-developed anti-PD-1 mAb HANSIZHUANG (serplulimab) in combination with bevacizumab and chemotherapy in patients with metastatic colorectal cancer (mCRC). Previously, the ASTRUM-015 study had launched its phase 3 stage and completed the first patient dosing in China and Indonesia. Colorectal cancer (CRC) is one of the most common malignant cancers globally. Over 1.9 million newly diagnosed cases and more than 900,000 deaths were estimated in 2022 [1]. It is estimated that, by 2040, the burden of CRC will increase to 3.2 million new cases per year (an increase of 63%) and 1.6 million deaths per year [2]. According to the latest report by National Cancer Center (NCC) of China, the incidence and mortality of CRC in China ranked 2nd and 4th among all cancers with 517,000 new cases and 240,000 deaths in 2022 [2]. In Japan, CRC ranks first in new incidence and second in mortality among all malignant tumors, with 146,000 new cases and 60,000 deaths reported in 2022 [1]. CRC often spreads before the initial tumour is detected. Based on molecular phenotype, mCRC is generally divided into two groups, dMMR/MSI-H and pMMR/MSS, with the latter accounting for around 95% of mCRC [3,4]. The standard of care for mCRC involves the combination of vascular endothelial growth factor (VEGF) inhibitor, such as bevacizumab, and systemic chemotherapy [5-7]. Still, sustained efficacy and prognosis remain to be improved. Several PD-1 inhibitors were shown to confer significant survival benefits for advanced CRC patients with dMMR/MSI-H [8,9]. However, pMMR/MSS mCRC, which accounts for a much higher proportion of mCRC, are considered “immune-cold tumours” characterised by low response rate to immunotherapy. To date, there has been no globally approved immunotherapy for the first-line treatment of pMMR/MSS mCRC, indicating a significant unmet medical need for this patient population. The company is continuing to explore immuno-oncology therapy for mCRC, with the goal of delivering highly effective treatment for a broad population of patients. ASTRUM-015 trial is a phase 2/3 study of HANSIZHUANG (serplulimab) plus bevacizumab and chemotherapy as first-line treatment for patients with mCRC. The results of the phase 2 stage of ASTRUM-015 were presented at the 2024 American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI) and 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. Recently, the results were also published online in Med, demonstrating the global recognition of serplulimab by the community. In conclusion, the addition of serplulimab to bevacizumab and chemotherapy conferred a numerically longer median progression-free survival, along with a manageable safety profile for mCRC patients as a whole, and those with MSS mCRC. These results support serplulimab plus bevacizumab and chemotherapy as a promising first-line treatment option for mCRC that warrants further investigation. Focus on lung and gastrointestinal cancer, the synergy of HANSIZHUANG (serplulimab) with in-house products of the company and innovative therapies are being actively promoted. The company has initiated over 10 clinical trials on immuno-oncology combination therapies in a wide variety of indications with more than 4,400 subjects enrolled. Moving forward, Henlius will actively promote the clinical progress of the phase 3 stage of ASTRUM-015. With the accelerated progress, HANSIZHUANG is expected to become the world's first anti-PD-1 mAb for previously untreated mCRC and fill the clinical gap in first-line immunotherapy in these patients. 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 and has been approved in China and several SEA countries. Up to date, 4 indications are approved for marketing, 2 marketing applications are under review in China and the EU, and more than 10 clinical trials are ongoing across the world. HANSIZHUANG was approved in China in March 2022 and has been approved by the National Medicinal Products Administration (NMPA) for the treatment of MSI-H solid tumours, squamous non-small cell lung cancer (sqNSCLC), extensive-stage small cell lung cancer (ES-SCLC), and esophageal squamous cell carcinoma (ESCC). The marketing applications of the first-line treatment for non-squamous non-small cell lung cancer (nsNSCLC) and ES-SCLC are under review by the NMPA and the European Medicines Agency (EMA), respectively. Focusing on lung and gastrointestinal cancer, the synergy of HANSIZHUANG with in-house products of the company and innovative therapies are being actively promoted. The company has initiated more than 10 clinical trials on immuno-oncology combination therapies in a wide variety of indications with more than 4,000 subjects enrolled in China, the U.S., Turkey, Poland, Georgia and other countries and regions. The results of 4 pivotal trials of HANSIZHUANG were published in the Journal of the American Medical Association (JAMA), Nature Medicine, Cancer Cell and British Journal of Cancer, respectively. Furthermore, HANSIZHUANG was respectively 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. On the other hand, serplulimab was granted orphan drug designations by the U.S. FDA and the EC for the treatment of SCLC, and its bridging head-to-head trial in the United States to compare HANSIZHUANG to standard of care atezolizumab (anti-PD-L1 mAb) for the first-line treatment of ES-SCLC is well under way. 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, 6 products have been launched in China, 3 have been approved for marketing in overseas markets, 24 indications are approved worldwide, and 3 marketing applications have been accepted for review in China 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 centre and Shanghai-based commercial manufacturing facilities certificated by China, the EU and U.S. GMP. Henlius has pro-actively built a diversified and high-quality product pipeline covering over 50 molecules 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: HERCESSI™ in the U.S., Zercepac® in Europe), a China-developed mAb biosimilar approved in China, Europe and U.S., HANDAYUAN (adalimumab), HANBEITAI (bevacizumab) and HANNAIJIA (neratinib), the innovative product HANSIZHUANG 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), and esophageal squamous cell carcinoma (ESCC), making it the world’s first anti-PD-1 mAb for the first-line treatment of SCLC. 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 喜欢本文内容 点击下方按钮·分享 ·收藏 ·点赞 ·在看