2024 WCLC | 复宏汉霖H药汉斯状小细胞肺癌领域研究数据发布

2024年9月9日，复宏汉霖（2696.HK）宣布，公司自主研发的创新型单抗H药汉斯状^®（斯鲁利单抗）小细胞肺癌领域最新研究结果以壁报形式在2024年世界肺癌大会（World Conference on Lung Cancer, WCLC）上发布。

H药汉斯状^®(斯鲁利单抗)是全球首个一线治疗小细胞肺癌的的抗PD-1单抗，已在中国、印尼、柬埔寨、泰国等地获批上市。目前，H药在中国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（sqNSCLC）、广泛期小细胞肺癌（ES-SCLC）及食管鳞状细胞癌（ESCC），覆盖肺癌、消化道肿瘤等高发肿瘤，累计惠及约8万名患者。

肺癌是全球最常见的恶性肿瘤之一。其中SCLC约占肺癌总数的15%^[1]，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ES-SCLC。截至目前，H药一线治疗ES-SCLC的适应症已在中国、印尼、柬埔寨和泰国获批，其欧盟上市许可申请（MAA）也已获得欧洲药品管理局 (EMA) 受理，有望于今年获批上市。同时，公司围绕H药在肺癌一线治疗全面布局，开展了针对sqNSCLC、ES-SCLC和LS-SCLC的多项国际多中心III期临床试验，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用于ES-SCLC的头对头桥接试验。

此次2024 WCLC大会的H药研究数据结果如下：

ASTRUM-005R研究

论文题目

ASTRUM-005R：斯鲁利单抗联合化疗一线治疗广泛期小细胞肺癌的真实世界多中心研究

试验设计

这是一项评估斯鲁利单抗联合化疗一线治疗ES-SCLC疗效和安全性的多中心、真实世界队列研究。纳入2022年4月至2024年4月在中国14家研究中心接受至少两个周期斯鲁利单抗联合依托泊苷和铂类一线治疗的ES-SCLC患者，并且至少进行一次疗效评估，主要研究终点为真实世界无进展生存期（rwPFS），次要终点包括总生存期（OS）、客观缓解率（ORR）、安全性。

结果

研究共入组538例患者进行疗效和安全性分析。中位年龄为63（范围:57.00~68.75）岁，467例（86.80%）为男性患者，406例（75.46%）患者有吸烟史。ECOG PS 为 0 或 1患者占多数（491，91.26%）。排除其他原发性肿瘤外，237例（44.05%）伴有合并症。肝转移和脑转移发生率分别为33.09%和21.56%。免疫联合化疗的中位治疗周期数为4（范围:4~6）周期，222例（41.26%）患者接受了超过4周期的治疗。

疗效数据显示，中位 rwPFS 为 9.1 个月（95% CI：8.1~9.7），1 年 rwPFS 率为 34.6%，超过 ASTRUM-005 研究亚裔人群的 1 年 PFS 率 28.2%，2 年 rwPFS 率为 11.3%。无肝转移患者的中位 rwPFS 为 9.7 个月（95%CI:8.8~12.8)显著优于肝转移患者的 7.4 个月（95%CI:6.2~8.9）（P < 0.0001），接受 >4 周期免疫联合化疗较接受 ≤4 周期免疫联合化疗治疗的患者中位 rwPFS显著提高（ 10.5 个月（95%CI:9.3~13.3）vs 6.7 个月（95% CI: 6.3~9.1）（P< 0.0001））。ORR为71.29%，OS尚未成熟。安全性方面，AESI发生率为38.85%，其中≥3级AESI为15.43%。

结论

斯鲁利单抗联合化疗一线治疗ES-SCLC的真实世界生存结果，为临床实践提供有价值的见解，验证了ASTRUM-005研究结果，为斯鲁利单抗联合依托泊苷和铂类一线治疗ES-SCLC补充有力证据。

一项回顾性研究

论文题目

免疫联合化疗对比化疗新辅助治疗局限期小细胞肺癌：一项回顾性研究

试验设计

研究纳入2018年1月至2023年10月接受新辅助PD-L1/PD-1抑制剂联合铂类化疗或单纯铂类化疗后进行手术切除的LS-SCLC患者。主要研究终点为病理完全缓解（pCR)和主要病理缓解(MPR)。次要研究终点包括R0切除率、降期率和无病生存期（DFS）。

结果

研究入组51例患者，其中26例接受免疫联合化疗新辅助治疗（14例(53.8%)接受斯鲁利单抗联合化疗新辅助治疗），25例接受化疗新辅助治疗，男性和女性患者分别有39名和12名。免疫联合化疗组和化疗组的平均年龄分别为 61.6（43.1~74.5）岁和 59.5（45.8~73.2）岁（表1）。

疗效数据显示，免疫联合化疗组和化疗组的pCR分别为 38.5%和 8.0%（OR 7.2，95% CI:1.4~37.3）。免疫联合化疗组和化疗组的MPR分别为 53.8%和12.0%（OR 8.6，95% CI:2.0~35.8）。免疫联合化疗组和化疗组R0切除率分别为92.3%和80.0%（OR 3.0,95% CI:0.5~17.2）。免疫联合化疗组较化疗组的病理降期率（88.5% vs 36.0%）和N2降期率（68.2% vs 24.0%）均提升（表2）。中位随访时间为17.2个月，免疫联合化疗组的中位DFS尚未达到，化疗组的中位DFS为11.3（95% CI:6.1~16.5）个月。

表1 患者基线特征

表2 研究结果

图1 不同新辅助治疗组的无病生存期结果

结论

新辅助免疫检查点抑制剂联合化疗治疗LS-SCLC显示出良好的疗效和可行性，可作为LS-SCLC潜在治疗选择，未来可进一步开展前瞻性随机对照试验证明免疫联合化疗新辅助治疗LS-SCLC的疗效与安全性，以优化LS-SCLC的治疗策略。

【参考文献】
[1] Eskandar A, Ahmed A, Daughtey M, et al. Racial and sex differences in presentation and outcomes of small cell lung cancer in the United States: 1973 to 2010[J].Chest, 2015,147(4): e164-e165.

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，已在中国和印度尼西亚获批上市。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。

Latest Results of Serplulimab in the Field of SCLC Released at 2024 WCLC

Shanghai, China, September 9, 2024 – Shanghai Henlius Biotech, Inc. (2696.HK) announced that the latest results of the company’s self-developed innovative anti-PD-1 monoclonal antibody (mAb), HANSIZHUANG (serplulimab) were released as poster presentations at 2024 World Conference on Lung Cancer (“WCLC 2024”) in the field of small cell lung cancer (SCLC).

HANSIZHUANG, the world's first anti-PD-1 mAb approved for the first-line treatment of SCLC, has been launched in China, Indonesia, Cambodia and Thailand. Up to date, it has been approved by the National Medical 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), broadly covering high-incidence tumours including lung cancer and gastrointestinal cancer, benefiting about 80,000 patients.

Lung cancer is one of the most common malignancies around the world. SCLC is the most aggressive subtype of lung cancer, accounting for around 15% of all lung cancer cases^[1]. The SCLC breaks down into limited stage small cell lung cancer (LS-SCLC) and ES-SCLC. To date, HANSIZHUANG has been approved for the first-line treatment of ES-SCLC in China, Indonesia, Cambodia and Thailand. Its Marketing Authorisation Application (MAA) for ES-SCLC has been validated by the European Medicines Agency (EMA), which is expected to be approved in 2024. In the meantime, Henlius has successively conducted a number of immuno-combination therapy clinical trials with serplulimab, including several global multi-centre phase 3 clinical trials regarding sqNSCLC, ES-SCLC and LS-SCLC, covering the full range of first-line treatments of lung cancer. Henlius has also initiated a head-to-head bridging 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.

The latest data of the studies released at 2024 WCLC conference are as follows:

ASTRUM-005R

Title

Real-world First-line Serplulimab-based Immunochemotherapy for Extensive-stage Small Cell Lung Cancer: The Multicenter ASTRUM-005R Study

Study design

This cohort study enrolled adult patients with ES-SCLC at 14 institutions in China from April 2022 to April 2024. These patients received at least two cycles of first-line serplulimab combined with chemotherapy and underwent at least one response assessment. The primary endpoint was the investigator-assessed real-world progression-free survival (rwPFS) according to RECIST version 1.1. Secondary endpoints included overall survival (OS), objective response rate (ORR), and safety profiles refer to CTCAE version 5.0.

Results

A total of 538 patients were enrolled and evaluated for both efficacy and safety. The participants had a median age of 63 years (range 57.00-68.75), with 467 (86.80%) being male and 406 (75.46%) having a history of smoking. Most patients (491, 91.26%) had an ECOG PS of 0 or 1. Comorbidities, excluding other primary tumors, were present in 44.05% (237 patients). Liver and brain metastases were observed in 33.09% (n=178) and 21.56% (n=116), respectively. The median number of immunochemotherapy cycles was 4 (range 4-6), with 41.26% (n=222) receiving more than four cycles. The median rwPFS was 9.1 months (95% CI 8.1-9.7), with a 1-year rwPFS rate of 34.6%, surpassing the 1-year PFS rate of 28.2% reported for the Asian in the ASTRUM-005 study. Besides, the 2-year rwPFS rate was shown to be 11.3%. The median rwPFS was 9.7 months (95% CI 8.8-12.8) in patients without liver metastasis, significantly longer than the 7.4 months (95% CI 6.2-8.9) in patients with liver metastasis (P < 0.0001). Patients who received >4 cycles of immunochemotherapy had a median rwPFS of 10.5 months (95% CI 9.3-13.3), which was significantly longer than the 6.7 months (95% CI 6.3-9.1) in patients who received ≤4 cycles (P < 0.0001). The OS was not yet mature, and the ORR was 71.29%. The occurrence frequency of adverse event of special interest (AESI) was 38.85% (421 events), in which grade ≥3 AESIs occupied 15.43%.

Conclusion

The ASTRUM-005R study provides additional empirical evidence to support the therapeutic value of serplulimab plus chemotherapy and complements the pivotal data from the ASTRUM-005 clinical trial.

A retrospective study

Title

Is neoadjuvant chemoimmunotherapy better than chemotherapy in patients with limited-stage small cell lung cancer: a retrospective comparative study

Study design

Patients with LS-SCLC who received neoadjuvant PD-L1/PD-1 inhibitor plus platinum-based chemotherapy or platinum-based chemotherapy alone followed by surgery between Jan 2018 and Oct 2023 in our institute were included. The primary endpoints were pathologic complete response rate and major pathologic response. The second endpoints were R0 resection rate, downstaging rate and disease-free survival.

Results

Of the 51 eligible patients, 26 received neoadjuvant chemoimmunotherapy and 25 received neoadjuvant chemotherapy (Table 1). There were 39 males and 12 females across both groups combined. Mean (range) age at diagnosis was 61.6 years (43.1-74.5) for the chemoimmunotherapy group and 59.5 years (45.8-73.2) for chemotherapy group. Pathologic complete response rate was 38.5% (10/26) in chemoimmunotherapy group versus 8.0% (2/25) in chemotherapy group (OR 7.2, 95% CI 1.4-37.3) (Table 2). Major pathologic response rate was 53.8% (14/26) in chemoimmunotherapy group versus 12.0% (3/25) in chemotherapy group (OR 8.6, 95% CI 2.0-35.8). R0 resection rate was 92.3 (24/26) in chemoimmunotherapy group versus 80.0% (20/25) in chemotherapy group (OR 3.0, 95% CI 0.5-17.2). Pathologic downstaging rate (88.5% vs 36.0) and N2 downstaging rate (68.2 vs 24.0) were higher in chemoimmunotherapy group. After a median follow up of 17.2 months, median DFS was not reached in chemoimmunotherapy group versus 11.3 (95% CI, 6.1-16.5) months in chemotherapy group.

Conclusion

Neoadjuvant immune checkpoint inhibitors (ICIs) combined with chemotherapy demonstrated promising efficacy and feasibility, and are a potential strategy for the management of LS-SCLC. Further prospective randomized controlled trials are necessary to clearly define the benefit of neoadjuvant chemoimmunotherapy and optimize LS-SCLC treatment.

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 Indonesia. 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