斯鲁利单抗注射液为复宏汉霖自主开发的创新型抗PD-1单抗，目前已获得中国、美国、欧盟等国家和地区的临床试验批准，共计开展10项肿瘤免疫临床试验，全面覆盖肺癌、食管癌、肝细胞癌、胃癌、头颈癌等高发大瘤种。2021年3月，斯鲁利单抗注射液用于经标准治疗失败的、不可切除或转移性高度微卫星不稳定型或错配修复缺陷型（MSI-H/dMMR）实体瘤的关键性II期临床研究达到主要研究终点，显示出产品在该适应症上良好的疗效及安全性。 目前，斯鲁利单抗针对MSI-H实体瘤适应症的上市注册申请（NDA）已正式获得国家药品监督管理局（NMPA）受理，并拟纳入优先审评程序。

以下为斯鲁利单抗（HLX10）的数据发表详情：

HLX10-010-MSI201

●  论文题目

Efficacy and safety of HLX10, a novel anti-PD-1 antibody, in patients with previously treated unresectable or metastatic microsatellite instability-high or mismatch repair-deficient solid tumors: a single-arm, multicenter, phase 2 study.

● 联合主要研究者

秦叔逵，中国人民解放军南京八一医院；李进，上海东方医院

● 展示形式

摘要及壁报

● 摘要编号

2566

● 试验设计

本研究是一项在标准治疗失败的、不可切除或转移性高度微卫星不稳定型或错配修复缺陷型实体瘤患者中进行的旨在评价HLX10疗效、安全性及耐受性的单臂、开放、多中心、II期临床试验。纳入的患者每两周静脉注射3 mg/kg HLX10，最多持续两年，直到疾病进展，出现不可接受的毒性或患者退出。该试验的主要终点为独立影像评估委员会（IRRC）依据RECIST v1.1标准评估的客观缓解率（ORR）。

● 试验结果

1）有效性

a）主要终点

本试验共入组108名患者，其中68名经中心实验室或研究中心确认MSI-H的患者被纳入主要疗效分析人群。主要疗效分析人群中，经独立影像评估委员会评估的ORR为38.2%（95% CI: 26.7%, 50.8%; 2例完全缓解）。

b） 次要终点

次要疗效终点包括研究者评估的客观缓解率，持续缓解时间（DoR），无进展生存期（PFS），总生存期（OS）。中位DoR，PFS及OS尚未达到。

2）安全性

结果表明，HLX10具有良好的安全性和耐受性。

● 结论

HLX10在标准治疗失败的MSI-H/dMMR实体瘤患者中展现了显著的抗肿瘤活性和较好的安全性。作为一种有效的组织不确定类癌症药物，HLX10有望改善患者的临床疗效。

HLX10-011-CC201

●  论文题目

Efficacy and safety evaluation of HLX10 (a recombinant humanised anti-PD-1 monoclonal antibody) combined with albumin-bound paclitaxel in patients with advanced cervical cancer who have progressive disease or intolerable toxicity after first-line standard chemotherapy: a single-arm, open-label, phase 2 study.

● 主要研究者

吴令英，中国医学科学院肿瘤医院

● 展示形式

摘要

● 摘要编号

e17510

● 试验设计

本研究是一项在一线标准化疗失败的晚期宫颈癌患者中评估HLX10联合白蛋白紫杉醇疗效、安全性及耐受性的单臂、开放、多中心、分两阶段的II期临床试验。纳入的患者每三周静脉输注HLX10（4.5 mg/kg）和白蛋白紫杉醇（260 mg/m ² ）。该试验的主要终点为独立影像评估委员会（IRRC）依据RECIST v1.1标准评估的客观缓解率（ORR）。

● 试验结果

试验第一阶段为安全导入及初步疗效探索期，共入组21名患者，其平均综合阳性分数（CPS）为39.33。经IRRC及研究者评估的ORR分别为52.4%（95% CI: 29.8%, 74.3%）和42.9%（95% CI: 21.8%, 66.0%）。试验表明，HLX10具有良好的安全性和耐受性。

● 结论

第一阶段的试验结果显示HLX10联合白蛋白紫杉醇在一线标准化疗失败的晚期宫颈癌患者中展现了较好的疗效和安全性。

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3款产品，在欧盟上市1款产品，3款产品获得中国上市注册申请受理。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研发中心，按照国际GMP标准进行生产和质量管控，位于上海徐汇的生产基地已获得中国和欧盟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单抗斯鲁利单抗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，欧盟商品名：Zercepac^®）、公司首个自身免疫疾病治疗产品汉达远^®（阿达木单抗）相继获批上市，创新产品斯鲁利单抗MSI-H实体瘤的上市注册申请已纳入优先审评审批程序，HLX04贝伐珠单抗及HLX01利妥昔单抗类风湿关节炎新适应症的上市注册申请也正在审评中。公司亦同步就10个产品、8个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国家市场开展20多项临床试验，产品对外授权覆盖全球近100个国家和地区。

Henlius Has Released Two Clinical Studies of Anti-PD-1 mAb Serplulimab for the First Time at 2021 ASCO Annual Meeting

Shanghai, China, June 7 th , 2021 –Shanghai Henlius Biotech, Inc. (2696.HK) announced that the company released the results of two phase 2 clinical studies (HLX10-010-MSI201& HLX10-011-CC201) of Serplulimab injection in patients with microsatellite instability-high or mismatch repair-deficient (MSI-H/dMMR) solid tumours and advanced cervical cancer (CC) at 2021 American Society of Clinical Oncology (ASCO) Annual Meeting for the first time.

Serplulimab injection is an innovative anti-PD-1 mAb independently developed by Henlius. Up to now, Serplulimab have been approved for clinical trials in China, the United States, the European Union, as well as other countries and regions. A total of 10 immuo-oncology therapy clinical studies of Serplulimab have been conducted to evaluate its safety and efficacy in a variety of most common tumours that cover lung cancer, esophageal cancer, hepatocellular cancer, gastric cancer, head and neck cancer, etc. In March 2021, the pivotal phase 2 study of Serplulimab in patients with unresectable or metastatic microsatellite instability-high or mismatch repair-deficient (MSI-H/dMMR) solid tumours who have progressed on or been intolerant to standard therapies met the primary endpoint, demonstrating the good efficacy and safety of Serplulimab.As of now, the New Drug Application (NDA) of serplulimab injection for the treatment of MSI-H solid tumors has been accepted by the National Medical Products Administration (NMPA) and proposed to be granted priority review .

Details of the two studies are as follows:

HLX10-010-MSI201

● Title

Efficacy and safety of HLX10, a novel anti-PD-1 antibody, in patients with previously treated unresectable or metastatic microsatellite instability-high or mismatch repair-deficient solid tumors: a single-arm, multicentre, phase 2 study.

● Co-Leading PI

Shukui Qin, MD, PhD, Chinese People's Liberation Army Cancer Center of Nanjing Bayi Hospital; Jin Li, MD, PhD, Shanghai East Hospital

● Form

Abstract and Poster

● Abstract No.

2566

● Study Design

This single-arm, open-label, multi-centre, phase 2 study aimed to evaluate the efficacy, safety, and tolerability of HLX10 in patients with unresectable or metastatic microsatellite instability-high or mismatch repair-deficient solid tumours who have progressed on or been intolerant to standard therapies. Eligible patients were recruited to receive 3 mg/kg HLX10 every two weeks intravenously for up to 2 years until disease progression, unacceptable toxicity, or patient withdrawal. The primary efficacy endpoint was objective response rate (ORR) assessed by independent radiological review committee (IRRC) per RECIST v1.1.

● Results

1) Efficacy

a) Primary endpoint

108 patients were enrolled and 68 with MSI-H confirmed by central laboratory or study sites were included in the main efficacy analysis population. IRRC assessed ORR was 38.2% (95% CI: 26.7%, 50.8%; 2 complete response) in the main efficacy analysis population.

b) Secondary endpoints

Secondary efficacy endpoints included ORR assessed by investigators, duration of response (DoR), progression-free survival (PFS), and overall survival (OS). Median DoR, PFS and OS have not been reached.

2) Safety

The results demonstrated that HLX10 was safe and well-tolerated.

● Conclusion

HLX10 provides encouraging antitumor activity with a manageable safety profile in patients with MSI-H/dMMR solid tumors who have progressed on or been intolerant to standard therapies. As an effective tissue-agnostic treatment, HLX10 possesses the potential to improve patients’ clinical outcomes.

HLX10-011-CC201

● Title

Efficacy and safety evaluation of HLX10 (a recombinant humanised anti-PD-1 monoclonal antibody) combined with albumin-bound paclitaxel in patients with advanced cervical cancer who have progressive disease or intolerable toxicity after first-line standard chemotherapy: a single-arm, open-label, phase 2 study.

● Leading PI

Lingying Wu, MD, PhD, Cancer Hospital Chinese Academy of Medical Science

● Form

Abstract

● Abstract No.

e17510

● Study Design

This is a single-arm, open-label, multi-centre, two-stage phase 2 study, aimed to evaluate the clinical efficacy of HLX10 in combination with albumin-bound paclitaxel for the treatment of advanced cervical cancer patients who have failed to respond to the first-line standard chemotherapy. Eligible patients were enrolled and given intravenous infusion of HLX10 (4.5 mg/kg) plus albumin-bound paclitaxel (260 mg/m ² ) every 3 weeks. The primary efficacy endpoint was objective response rate (ORR) assessed by independent radiological review committee (IRRC) per RECIST v1.1.

● Results

The stage one of this study was a safety run-in and preliminary efficacy exploration study. 21 patients were enrolled with an average Combined Positive Score (CPS) of 39.33. The ORR assessed by IRRC and investigators were 52.4% (95% CI: 29.8%, 74.3%) and 42.9% (95% CI: 21.8%, 66.0%), respectively. The results demonstrated that HLX10 was safe and well tolerated.

● Conclusion

Stage one results demonstrated a manageable safety profile and encouraging efficacy of HLX10 plus albumin-bound paclitaxel in advanced cervical cancer patients who have failed to respond to the first-line standard chemotherapy.

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, 3 products have been launched in China, 1 in the European Union (EU), the New Drug Applications (NDAs) of 3 products 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 commercialisation. It has established global R&D centers and a Shanghai-based manufacturing facility certificated by China and the EU Good Manufacturing Practice (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 serplulimab (anti-PD-1 mAb) as backbone. Apart from the launched products 汉利康^® (rituximab), the first China-developed biosimilar, 汉曲优^® (trastuzumab, Zercepac^® in the EU), the first China-developed mAb biosimilar approved both in China and in the EU and 汉达远^®(adalimumab), the Company's first product indicated for autoimmune diseases, the NDA of innovative product serplulimab indicated for MSI-H solid tumors has been granted priority review, and the NDAs of HLX04 (bevacizumab) and HLX01 (rituximab) for the treatment of rheumatoid arthritis are also under review. What's more, Henlius has conducted over 20 clinical studies for 10 products and 8 combination therapies worldwide, expanding its presence in major market as well as emerging market.