近日，复宏汉霖H药 汉斯状®（斯鲁利单抗，serplulimab）联合汉贝泰®（贝伐珠单抗，HLX04）在晚期肝细胞癌（HCC）患者中开展的II期临床研究数据发表于肝病学知名期刊Liver Cancer（IF 12.43）。研究结果显示，H药联合汉贝泰®在先前经受治疗的晚期肝细胞癌患者中具有良好的安全性，并展现出明显的抗肿瘤活性。
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本研究是一项开放标签、多中心临床II期研究，旨在评估斯鲁利单抗单药或联合HLX04在晚期肝细胞癌患者中的安全性、耐受性和疗效。考虑到数据成熟度，本次刊文仅披露联合疗法在既往经受过治疗患者中的数据（即A、B两组）。患者每2周静脉输注一次斯鲁利单抗3 mg/kg联合不同剂量的HLX04 5 mg/kg（A组）或10 mg/kg（B组）。主要终点为安全性和耐受性，次要终点为客观缓解率（ORR）、总生存期（OS）、无进展生存期（PFS）、持续缓解时间（DoR）等。截止到2021年4月8日，本研究中A（n=20）、B（n=21）组斯鲁利单抗联合贝伐珠单抗具有良好的安全性和耐受性，经IRRC评估的ORR分别为30.0%（95% CI：11.9，54.3）、14.3%（95% CI：3.0，36.3），A组中位PFS为2.2个月（95% CI：1.4，5.5），B组中位PFS为4.1个月（95% CI：1.5，NE）。该研究结果的安全性与抗PD-1单抗或贝伐珠单抗单药以及阿替利珠单抗联合贝伐珠单抗在既往未经受治疗的晚期HCC患者中的安全性研究结果一致，并相较于现有同类头部抗PD-(L)1产品显示出相似或更好的疗效。该研究数据可为抗PD-1单抗联合抗血管生成药物在HCC二线及以上的临床实践提供依据。目前，公司H药联合贝伐珠单抗以及联合HLX07（抗EGFR单抗）一线治疗晚期肝细胞癌患者的II期临床试验申请已经获国家药监局批准。
H药斯鲁利单抗是复宏汉霖首个自主研制的创新型单抗药，目前已获批用于治疗微卫星高度不稳定（MSI-H）实体瘤。此外，H药联合化疗一线治疗鳞状非小细胞肺癌（sqNSCLC）、广泛期小细胞肺癌（ES-SCLC）和食管鳞状细胞癌（ESCC）的NDA已获得NMPA受理。以H药为基础，公司在全球开展多元化的肿瘤免疫联合疗法，并充分运用自有管线覆盖肿瘤特异性靶点、抗血管生成靶点和肿瘤免疫靶点等，助力H药与单抗、化疗等治疗手段开展联合治疗。以临床需求为导向，公司就H药在消化道肿瘤和肺癌领域进行了差异化、多维度布局，适应症广泛覆盖肺癌、肝细胞癌、食管鳞癌、头颈鳞癌和胃癌等高发大癌种，在全球范围内累计入组逾3100名受试者。
未来，复宏汉霖也将推动更多创新产品的临床研究，积极开展联合治疗方案、创新靶点双特异性抗体以及抗体偶联药物（ADC）等产品的布局，期待早日为更多患者带来质高价优的生物药。
关于Liver Cancer
为了更好地了解恶性肿瘤的原因、机制和治疗，Liver Cancer杂志基于日渐增长的肝癌发病率，重点关注疾病的分子致癌、预防、监测、诊断和治疗（包括分子靶向治疗），从而为国际社会的研究人员和临床医生提供研究成果分享的平台。Liver Cancer以研究和综述类文章为主，旨在发表与肝癌相关的人体或实验模型的临床和转化研究。
关于H药斯鲁利单抗
H药斯鲁利单抗为重组人源化抗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。
2022年3月，H药正式获批用于治疗微卫星高度不稳定（MSI-H）实体瘤。围绕H药，复宏汉霖积极推进其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11项肿瘤免疫联合疗法临床试验，广泛覆盖肺癌、食管癌、头颈鳞癌和胃癌等适应症，全面覆盖肺癌一线治疗。截至目前，H药已于中国、土耳其、波兰、格鲁吉亚等国家和地区累计入组超3100人，其中2项国际多中心临床试验入组高加索人种的比例超过30%，是拥有国际临床数据较多的抗PD-1单抗之一。H药联合化疗一线治疗鳞状非小细胞肺癌（sqNSCLC）、广泛期小细胞肺癌（ES-SCLC）和食管鳞状细胞癌（ESCC）的NDA已获得NMPA受理，H药有望成为全球首个一线治疗SCLC的抗PD-1单抗。此外，该药入选《2022 CSCO小细胞肺癌诊疗指南》作为ES-SCLC治疗推荐，其治疗小细胞肺癌（SCLC）也已获得美国FDA孤儿药资格认定。
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，13项适应症获批，5个上市注册申请获得中国药监局受理。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药斯鲁利单抗的肿瘤免疫联合疗法。继国内首个生物类似药利妥昔单抗、中国首个自主研发的中欧双批单抗药物曲妥珠单抗，欧洲商品名：Zercepac®，澳大利亚商品名：Tuzucip®和Trastucip®、阿达木单抗和贝伐珠单抗相继获批上市，创新产品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。
Phase 2 Study of the PD-1 Inhibitor Serplulimab Plus the Bevacizumab Biosimilar HANBEITAI in Patients with Advanced Hepatocellular Carcinoma Published in Liver Cancer
Recently, Liver Cancer (IF 12.43), a prestigious journal in hepatology, published the phase 2 study of HANSIZHUANG (serplulimab) plus HANBEITAI (bevacizumab, HLX04) in patients with advanced hepatocellular carcinoma (HCC). Serplulimab plus HLX04 demonstrated a manageable safety profile and favorable antitumor activity in patients with previously treated advanced HCC.
This open-label, multi-centre phase 2 study aimed to assess the safety, tolerability, and efficacy of serplulimab in combination with HLX04 for patients with advanced HCC. Given the data maturity, this publication only discloses results from patients treated with serplulimab plus HLX04 who had received prior systemic therapy (i.e., groups A and B). Patients received intravenous infusions of serplulimab 3 mg/kg and intravenous infusions of HLX04 at either 5 mg/kg (group A) or 10 mg/kg (group B) every 2 weeks. The primary endpoints were safety and tolerability. Secondary endpoints included objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and duration of response (DoR), among others.
As of April 8, 2021, results from both groups (group A, n=20; group B, n=21) demonstrated that serplulimab plus HLX04 was safe and well-tolerated. As assessed by an independent radiological review committee (IRRC), the ORR was 30.0% (95% CI, 11.9–54.3) in group A and 14.3% (95% CI, 3.0–36.3) in group B. Median PFS was 2.2 months (95% CI, 1.4–5.5) in group A and 4.1 months (95% CI, 1.5–NE) in group B. The safety profile for serplulimab plus HLX04 in this study were consistent with the safety profiles of the two drug classes and with that of atezolizumab plus bevacizumab in previously untreated patients with advanced HCC. The efficacy outcomes for serplulimab plus HLX04 were similar or better compared with other anti-PD-(L)1 therapies. These results provide evidence for the use of anti-PD-1 monoclonal antibody (mAb) in combination with anti-angiogenic agents in the second- or later-line treatment of HCC in clinical practice. An investigational new drug application for a phase 2 trial of serplulimab in combination with HLX04 and HLX07 (innovative anti-EGFR mAb) for the first-line treatment of unresectable or metastatic HCC has been approved by the National Medical Products Administration (NMPA).
HANSIZHUANG (serplulimab) is the first innovative mAb developed by Henlius. It has been approved by the NMPA for the treatment of microsatellite instability-high (MSI-H) solid tumours. 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. Henlius actively promotes HANSIZHUANG in conjunction with in-house products of the company such as tumour-specific target, angiogenesis target, immunotherapeutic target, etc. and chemotherapy drugs to conduct immune combination therapies. Underpinned by the patient-centric strategy, Henlius has carried out a differentiated and multi-dimensional layout in the field of gastrointestinal cancer and lung cancer, covering a wide variety of indications, such as lung cancer, HCC, ESCC, head and neck squamous cell carcinoma and gastric cancer, etc. Up to date, more than 3,100 subjects have been enrolled worldwide for HANSIZHUANG clinical trials.
As Henlius moves forward, it will continue to conduct clinical studies on more innovative products, proactively exploring immuno-oncology combination therapy, bispecific antibodies and antibody-drug conjugates (ADC), with the aim of bringing affordable and high-quality innovative biologics to patients around the world.
About Liver Cancer
Liver cancer has a very high prevalence among cancers in general and is one of the most common causes of death worldwide. Based on these facts, the journal Liver Cancer serves the growing need to better understand the causes, mechanisms, and therapy of the malignancy. It provides the international community of researchers and clinicians with a platform for their research results, focusing on molecular carcinogenesis, prevention, surveillance, diagnosis, and treatment, including molecular targeted therapy, of the disease. Liver Cancer publishes clinical and translational research related to the field of liver cancer in both humans and experimental models in the form of original and review articles.
About HANSIZHUANG
HANSIZHUANG (recombinant humanized 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 tumors in March 2022 and actively promotes its synergy with in-house products of the company and innovative therapies. 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 worldwide 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 Caucasian 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 was also granted orphan drug designation by the FDA for treatment of 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 in global, 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.
【参考文献】
Ren Z, et al. Phase 2 Study of the PD-1 Inhibitor Serplulimab Plus the Bevacizumab Biosimilar HLX04 in Patients with Previously Treated Advanced Hepatocellular Carcinoma. Liver Cancer 2022. Advance online publication. doi: 10.1159/000526638
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