小细胞肺癌一线治疗新突破——复宏汉霖PD-1抑制剂研究达到OS主要研究终点

2021年12月7日，复宏汉霖（2696.HK）宣布公司自主研制的创新型PD-1抑制剂斯鲁利单抗联合化疗在既往未接受过治疗的广泛期小细胞肺癌（ES-SCLC）的一项随机、双盲、国际多中心III期临床研究（NCT04063163）第一次期中分析达到了总生存期（OS）的主要研究终点。当前全球暂无抗PD-1单抗获批用于ES-SCLC的治疗。

该研究主要目的是在既往未接受过治疗的ES-SCLC患者中研究斯鲁利单抗联合化疗的有效性和安全性。由独立数据监察委员会（Independent Data Monitoring Committee, IDMC）进行的第一次预设中期分析显示，斯鲁利单抗联合化疗对比化疗显示出明显的OS改善，达到预设的优效性标准，且安全性良好，未发现新的安全性信号，IDMC建议以本次的有效性分析结果提前申报。

NCT04063163研究主要研究者、吉林省癌症中心主任、吉林省肺癌诊疗中心主任、吉林省肿瘤医院恶性肿瘤临床研究一体化诊疗中心主任程颖教授表示：“非常兴奋看到此次斯鲁利单抗广泛期小细胞肺癌的III期研究的OS已经达到预设的主要研究终点，疗效和安全性得到充分验证，能够为患者带来明显获益。这是首个由中国研究者牵头开展的针对ES-SCLC适应症的最大规模PD-1单抗国际多中心临床研究。高质量的临床数据充分显现出我国的自主创新能力和临床试验水平。非常期待斯鲁利单抗能够早日上市，代表中国具有自主知识产权的药物站上国际舞台，为全球小细胞肺癌患者带去新的治疗选择。”

NCT04063163研究的IDMC主席、中国医学科学院肿瘤医院王洁教授表示：“SCLC是一种侵袭性强、预后较差的肺癌类型，其中ES-SCLC癌细胞极易发生转移。现阶段ES-SCLC治疗仍以化疗或化疗联合PD-L1抑制剂为主，化疗治疗后容易进展，5年生存率一般不会超过5%，患者预后长期未能得到显著改善。此次，复宏汉霖斯鲁利单抗III期研究的试验结果让我们看到了PD-1一线治疗ES-SCLC的新希望。”

另一位IDMC成员，来自意大利都灵大学医学肿瘤中心的Giorgio Scagliotti教授表示：“全球针对SCLC的临床可选方案非常有限，尤其是抗PD-1单抗相关治疗方案，目前仅有化疗或抗PD-L1单抗联合化疗作为NCCN诊疗指南一线治疗方案。复宏汉霖斯鲁利单抗针对ES-SCLC在亚洲、欧洲多个国家同步开展了国际多中心III期临床研究，全球共入组580多例受试者，期待斯鲁利单抗凭借国际多中心临床数据进入国际市场，惠及全球更多患者。”

复宏汉霖总裁朱俊先生表示：“斯鲁利单抗是复宏汉霖自主研制的创新单抗产品，公司进行了肺癌一线全面布局。基于大量未满足的临床需求，公司在SCLC领域进行重要战略部署。此次III期研究结果优异，有望助力斯鲁利单抗成为全球首个一线治疗SCLC的抗PD-1单抗产品，显著改善患者的生存获益。公司聚焦全球及中国高发癌种，未来也会积极推进斯鲁利单抗的免疫联合疗法和国际临床研究，为全球更多患者带去福音。”

SCLC恶性程度高，现有治疗手段有限

据GLOBOCAN 数据显示，肺癌是全球发病率第二大高发癌种，2020年肺癌约占全球癌症发病率的11.4%，我国约有超过81万新发肺癌病例，位居肿瘤发病率和死亡率榜首。SCLC占肺癌总数的15%-20%，是肺癌中侵袭性最强的亚型，分为局限期小细胞肺癌（LS-SCLC）和广泛期小细胞肺癌，多数患者在确诊时已处于广泛期。ES-SCLC患者肿瘤生长迅速，临床恶化快，总体预后不良。部分患者因肿瘤转移广泛，体能状况差仅能进行支持治疗，故生存期更短。

过去的20年间，依托泊苷联合卡铂或顺铂一直是ES-SCLC患者的标准一线治疗，一线化疗80%的局限期患者和几乎所有广泛期患者在一年内复发，复发后生存期约4-5个月。免疫检查点抑制剂的出现为临床提供了新的治疗选择，目前抗PD-L1单抗联合化疗已陆续被最新版NCCN指南和CSCO指南推荐为ES-SCLC一线治疗方案。然而免疫治疗在ES-SCLC领域的应用仍面临一系列挑战，近年来多款PD-1产品在SCLC领域接连折戟，未使ES-SCLC患者真正获益，因此迫切需要更为有效的PD-1抑制剂一线治疗方案。

以患者需求为核心，覆盖全类型肺癌一线治疗

围绕“Combo+Global”（联合治疗+国际化）差异化开发战略，斯鲁利单抗已获得中国、美国、欧盟等国家及地区的临床试验许可，目前共开展10项肿瘤免疫疗法临床试验，适应症广泛覆盖肺癌、肝细胞癌、食管癌、头颈癌和胃癌等高发大癌种，全球范围内累计入组约2300名受试者，也印证了国际市场对斯鲁利单抗质量的信心与认可。目前，斯鲁利单抗“泛癌种”治疗高度微卫星不稳定型（MSI-H）实体瘤适应症的上市注册申请也已于2021年4月获国家药监局（NMPA）受理并被纳入优先审评审批程序，有望于2022年上半年获批上市。

以斯鲁利单抗为基础，公司依据全球及中国癌症发病人群特点，重点聚焦肺癌和消化道肿瘤领域。复宏汉霖现已实现肺癌一线的全面临床布局，在鳞状非小细胞肺癌（sqNSCLC）、非鳞状非小细胞肺癌（nsNSCLC）和SCLC均就斯鲁利单抗开展试验，覆盖了超过90%的肺癌患者。基于其中一项在既往未接受治疗的局部晚期或转移性sqNSCLC患者中开展的随机、双盲、国际多中心III期临床试验，斯鲁利单抗一线治疗局部晚期或转移性sqNSCLC的上市注册申请已获得NMPA受理。未来，凭借丰富的国际临床研究数据，复宏汉霖将不断拓展斯鲁利单抗的国际布局，惠及全球更多患者。

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4款产品，在欧盟上市1款产品，3个产品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研发中心，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，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®）、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，HLX01利妥昔单抗类风湿关节炎新适应症、斯鲁利单抗鳞状非小细胞肺癌适应症的上市注册申请也正在审评中。公司亦同步就11个产品、8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。

Henlius’ Phase 3 clinical study of novel PD-1 inhibitor serplulimab for the treatment of first-line extensive-stage small cell lung cancer (ES-SCLC) meets primary study endpoint

Shanghai, China, December 7th, 2021 – Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first interim analysis met the primary study endpoint of the overall survival (OS) of the Phase 3 clinical study (NCT04063163) of its innovative PD-1 inhibitor serplulimab in combination with chemotherapy in previously untreated patients with extensive-stage small cell lung cancer (ES-SCLC). There is no anti-PD-1 mAb approved for the treatment of extensive-stage small cell lung cancer worldwide.

The study’s main purpose is to explore the efficacy and safety of serplulimab in combination with chemotherapy in previously untreated patients with ES-SCLC. Based on the results of a pre-defined interim analysis conducted by the Independent Data Monitoring Committee (IDMC), serplulimab in combination with chemotherapy showed a significant improvement in OS against chemotherapy, which met the pre-defined efficacy criteria, with good safety and no detection of a new safety signal. IDMC suggested that the company can hence communicate with healthy authority.

Professor Ying Cheng, the principal investigator of NCT04063163, Director of Jilin Department of Medical Oncology Cancer Center, Jilin Province Lung Cancer Diagnosis and Treatment Center, and Jilin Cancer Hospital Malignant Tumor Clinical Research Integrated Diagnosis and Treatment Center, said, “I’m very excited to see that the Phase 3 study of serplulimab in ES-SCLC has met its primary endpoint OS, and its efficacy and safety have been fully validated. This study is the first and largest ES-SCLC international multi-center clinical study led by Chinese researchers for anti-PD-1 mAb. The favorable clinical results show China’s ability to innovate with a high clinical trial level. We are looking forward to serplulimab launching as soon as possible, which brings a drug with Chinese independent intellectual property to patients with small cell lung cancer all over the world.”

IDMC Chairman of NCT04063163, and Cancer Hospital Chinese Academy of Medical Sciences, Professor Jie Wang, said, “SCLC is a type of lung cancer with strong invasion and poor prognosis, among which ES-SCLC cancer cells are prone to metastasis. At present, ES-SCLC is still mainly treated with chemotherapy or chemotherapy combined with PD-L1 inhibitors. It is easy to progress after chemotherapy, and the 5-year survival rate is generally less than 5%. The prognosis has not been improved for a long time. The results of the Phase 3 trial of serplulimab bring a new option for anti-PD-1 mAb as a first-line ES-SCLC therapy.”

Professor Giorgio Scagliotti from the Medical Oncology, University of Turin in Italy, one of IDMC members, said, “There are limited choices for SCLC clinical treatment, especially in anti-PD-1 mAb. Currently, the first-line treatment is chemotherapy or anti-PD-L1 mAb combined with chemotherapy according to the NCCN guidelines. This international multi-center Phase 3 clinical study on ES-SCLC has been carried out in many countries in Asia and Europe, with more than 580 subjects worldwide. It is believed that by means of international multi-center clinical data, serplulimab will enter the international market and benefit more patients worldwide.”

Mr. Jason Zhu, President of Henlius, said, “Serplulimab is an innovative mAb independently developed by Henlius, and the company has carried out a comprehensive first-line treatment layout for lung cancer. Based on the large number of unmet clinical needs, the company has invested in SCLC. The excellent results of this Phase 3 study are expected to contribute serplulimab in becoming the first anti-PD-1 mAb for the first-line treatment of SCLC, which will significantly improve the overall prognosis. Henlius focuses on high-incidence cancers both globally and in China. In the future, we will proactively promote the combination immunotherapy of serplulimab and international clinical research, benefiting more patients around the world.”

SCLC is highly malignant, and the available treatment is limited

According to GLOBOCAN data, lung cancer (LC) is the second commonly diagnosed cancer globally and accounts for 11.4% of the global cancer incidence in 2020. It is estimated that there are 810,000 new cases with LC in China in 2020, and LC is the leading cause of cancer incidence and mortality. SCLC accounts for 15%-20% among LC, and is the most aggressive subtype of LC, which is divided into limited stage small cell lung cancer (LS-SCLC) and ES-SCLC. Most patients are already in extensive stage when diagnosed. Patients with ES-SCLC always have rapid tumour growth and poor prognosis. Some of them have shorter survival due to extensive tumor metastasis and poor physical status only with supportive care.

Over 20 years, etoposide plus carboplatin/cisplatin is still the standard of care for ES-SCLC, but 80% of patients with limited stage disease and almost all patients with extensive stage disease relapse within one year, with a median survival of only 4 to 5 months after relapse. The emergence of immune checkpoint inhibitors provides a new option. At present, anti-PD-L1 mAb combined with chemotherapy has been recommended by the latest NCCN guidelines and CSCO guidelines as the first-line treatment for ES-SCLC. However, the application of immunotherapy in ES-SCLC still faces challenges. In recent years, a number of PD-1 mAbs have failed in the area. Therefore, more effective first-line treatment of PD-1 inhibitors is urgently needed.

Centering on the unmet needs of patients, covering the first-line treatment of all types of lung cancer

Henlius has adopted a differentiated “Combo+Global” strategy on serplulimab. Currently, serplulimab has been approved for clinical trials in China, the United States, the European Union and other countries and regions. A total of 10 immuo-oncology therapies clinical trials of serplulimab are ongoing to evaluate its safety and efficacy in a wide variety of solid tumors that cover LC, hepatocellular carcinoma, esophageal carcinoma, head and neck squamous cell carcinoma and gastric cancer etc. Up to date, about 2300 patients have been enrolled worldwide, proving that the quality of serplulimab has built trust in foreign markets. In April, the New Drug Application (NDA) of serplulimab for the treatment of MSI-H solid tumours was accepted by the National Medical Products Administration (NMPA) and granted priority review, which is expected to be approved in the first half of 2022.

According to the characteristics of cancer patients both globally and in China, the company focus on lung cancer and gastrointestinal cancer with serplulimab as the backbone. Henlius has achieved a comprehensive first-line clinical layout of LC, and has carried out trials on serplulimab in sqNSCLC, non-squamous non-small cell lung cancer and SCLC, covering more than 90% of lung cancer patients. Based on a randomized, double-blind, international multi-center Phase 3 clinical trials conducted in previously untreated patients with locally advanced or metastatic sqNSCLC, the NDA of serplulimab for first-line treatment of locally advanced or metastatic sqNSCLC has been accepted by the NMPA. In the future, with abundant international clinical research data, Henlius will continue expanding the international distribution of serplulimab and benefit more patients around the world.

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, 4 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 centres 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, 汉达远® (adalimumab) and 汉贝泰® (bevacizumab), the NDA of innovative product serplulimab indicated for MSI-H solid tumors has been granted priority review, and the NDAs of HLX01 (rituximab) for the treatment of rheumatoid arthritis and serplulimab for the treatment of squamous non-small cell lung cancer are also under review. What’s more, Henlius has conducted over 20 clinical studies for 11 products and 8 combination therapies worldwide, expanding its presence in major market as well as emerging market.

联系方式

媒体：PR@Henlius.com

投资者：IR@Henlius.com