Cancer Communications刊登复宏汉霖H药 汉斯状®小细胞肺癌国际多中心注册研究ASTRUM-005结果

肺癌是全球最常见的恶性肿瘤之一。小细胞肺癌（SCLC）占肺癌总数的15%-20%，具有恶性程度高、转移早、疾病进展迅速等特点，预后极差。SCLC分为局限期和广泛期，其中约30%-40%的患者确诊时处于局限期，其余处于广泛期。ASTRUM-005研究是一项随机、双盲、国际多中心的III期临床试验，旨在研究斯鲁利单抗对比安慰剂分别联合化疗一线治疗广泛期小细胞肺癌（ES-SCLC）的疗效和安全性。基于ASTRUM-005，H药 汉斯状^®已在中国、欧洲和东南亚等30多个国家和地区获批用于一线治疗ES-SCLC，为全球首个获批一线治疗小细胞肺癌的抗PD-1单抗。

研究中585例既往未接受过系统性治疗的ES-SCLC患者按2:1的比例随机分组（斯鲁利单抗组，n = 389；安慰剂组，n = 196），每三周一次接受静脉输注斯鲁利单抗4.5 mg/kg或安慰剂。所有患者均接受最多4周期的卡铂和依托泊苷治疗。主要终点是总生存期（OS）。此外，研究进行了探索性生物标志物分析，通过回归分析检验客观缓解率 （ORR）、OS和无进展生存期 （PFS）与基因突变或差异表达蛋白（differential expression proteins, DEPs）表达之间的关联，同时评估了血液学参数的预后价值。

至2022年6月13日数据截止时，在意向治疗人群中，斯鲁利单抗组和安慰剂组的中位OS分别为15.8个月和11.1个月（HR 0.62；95% CI: 0.50-0.76；描述性P < 0.001）。通过比较斯鲁利单抗组中达到客观缓解和未达客观缓解的患者的血清蛋白质组，鉴定出181个DEPs，并由此构建了基于15个蛋白表达水平的分子标志物组合（15-蛋白标志物组合）。研究结果显示，在斯鲁利单抗组中，较高的15-蛋白标志物组合评分与更长的OS和PFS显著相关（见下图）。此外，携带RB1基因突变或Notch通路突变的患者，与携带对应的野生型基因的患者相比，获得ORR、OS或PFS改善。基线中性粒细胞与淋巴细胞比值（NLR）和乳酸脱氢酶（LDH）水平则是ES-SCLC患者的独立预后因素。

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，截至目前，H药已获批用于治疗鳞状非小细胞肺癌（sqNSCLC）、广泛期小细胞肺癌（ES-SCLC）、食管鳞状细胞癌（ESCC）和非鳞状非小细胞肺癌（nsNSCLC）。未来，复宏汉霖将继续立足临床需求，持续进行创新探索，助力患者不断提高生存获益，并为全球患者带来更多高质量、可负担的治疗选择。

Updated results and biomarker analysis from the Pivotal Clinical Trial ASTRUM-005 of Serplulimab Published on Cancer Communications

Recently, the updated results and biomarker analysis of ASTRUM-005, Henlius’ international multi-centre phase 3 study of its innovative anti-PD-1 monoclonal antibody (mAb) HANSIZHUANG (serplulimab, trade name: Hetronifly^® in Europe) as first-line treatment for patients with extensive-stage small cell lung cancer (ES-SCLC) were published in Cancer Communications (IF 20.1), with Professor Ying Cheng from Jilin Province Cancer Hospital as the leading principal investigator of this study. The results of ASTRUM-005 were first presented at 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, and published in the Journal of the American Medical Association (JAMA), one of the top four medical journals in the world, in September 2022. At the recent 2025 ASCO Annual Meeting, the ASTRUM-005 study released 42.4 months of median follow-up data, disclosing a four-year overall survival (OS) rate of 21.9%. The updated results and exploratory biomarker analysis from ASTRUM-005 up to June 13, 2022, published in Cancer Communications this time, were first presented at the 2022 European Society for Medical Oncology Asia (ESMO Asia) Congress and the American Association for Cancer Research (AACR) Annual Meeting 2024, respectively.

Lung cancer is one of the most common malignancies worldwide. Small cell lung cancer (SCLC), which accounts for 15% to 20% of all lung cancers, is characterised by high malignancy, early metastasis, rapid progression, and poor prognosis. Among SCLC patients, approximately 30% to 40% are diagnosed at a limited stage, while the remaining cases are in extensive stage. ASTRUM-005 is a randomised, double-blind, international, multi-centre, phase 3 study aimed to compare the efficacy and safety of serplulimab, versus placebo in combination with chemotherapy in previously untreated ES-SCLC patients. Based on the pivotal clinical trial ASTRUM-005, HANSIZHUANG has been approved for the treatment of ES-SCLC in over 30 countries and regions, including China, Europe and Southeast Asia. HANSIZHUANG is the world’s first anti-PD-1 mAb for the first-line treatment of SCLC.

In ASTRUM-005, 585 patients with previously untreated ES-SCLC were randomised in a 2:1 ratio (serplulimab group, n = 389; placebo group, n = 196) to receive 4.5 mg/kg serplulimab or placebo intravenously every 3 weeks. All patients also received carboplatin and etoposide for up to 4 cycles. The primary endpoint was overall survival (OS). In addition, the associations between efficacy outcomes, including objective response rate (ORR), OS, and progression-free survival (PFS), and gene mutation status or differentially expressed proteins (DEPs) were examined with regression analysis in the exploratory biomarker analysis. Furthermore, the prognostic value of hematological parameters was evaluated.

By the data cutoff of June 13, 2022, in the intent-to-treat population, the median OS was 15.8 months in the serplulimab group versus 11.1 months in the placebo group (hazard ratio, 0.62; 95% confidence interval, 0.50-0.76; descriptive P < 0.001). We identified 181 DEPs by comparing the serum proteomes of responders versus non-responders in the serplulimab group and constructed a 15-protein signature. In the serplulimab group, patients with a higher 15-protein signature score were associated with significantly longer OS and PFS. Also, patients harboring tumor-suppressor retinoblastoma-1 (RB1) mutations or mutations in Notch pathway members showed improved ORR, OS, or PFS compared with their wild-type counterparts. Baseline neutrophil-to-lymphocyte ratio (NLR) and lactate dehydrogenase (LDH) level were independent prognosticators of patients with ES-SCLC.

Focusing on lung and gastrointestinal cancer, the synergy of HANSIZHUANG with in-house products of the company and innovative therapies are being actively promoted. Up to date, HANSIZHUANG has been approved  for the treatment of squamous non-small cell lung cancer (sqNSCLC), ES-SCLC, esophageal squamous cell carcinoma (ESCC) and non-squamous non-small cell lung cancer (nsNSCLC). In the future, Henlius will continue to focus on clinical needs, persist in innovative exploration, help patients improve survival benefits, and bring more high-quality, affordable treatment options to patients worldwide.

媒体：PR@Henlius.com

投资者：IR@Henlius.com