夯实持久生存获益，复宏汉霖H药汉斯状®非鳞非小最终分析数据获登Cancer Communications

近日，复宏汉霖自主研发的抗PD-1单抗H药汉斯状^®（斯鲁利单抗，欧洲商品名：Hetronifly^®）一线治疗晚期非鳞状非小细胞肺癌（nsqNSCLC）的III期临床（ASTRUM-002）研究最终生分析结果正式发表于国际顶尖肿瘤期刊Cancer Communications（影响因子：28.4）。研究结果显示，斯鲁利单抗联合化疗组的中位总生存期（mOS）达到26.8个月，此前该数据结果已作为重磅 LBA 摘要亮相 2025 年欧洲肿瘤内科学会（ESMO）年会，此次再登权威期刊进一步为H药一线治疗驱动基因阴性晚期nsq-NSCLC夯实了循证证据。

近4年长随访OS数据出炉，印证长期生存获益

ASTRUM-002研究是一项三臂、随机、双盲、多中心III期研究，旨在探索斯鲁利单抗联合化疗 ±HLX04（贝伐珠单抗）一线治疗驱动基因阴性晚期非鳞 NSCLC 的生存获益。研究共纳入636例既往未接受系统治疗的无 EGFR/ALK/ROS1 突变的局部晚期或转移性非鳞 NSCLC 患者，按1:1:1比例随机分配至三组：A组接受斯鲁利单抗联合HLX04（贝伐珠单抗）及化疗（卡铂-培美曲塞），B组接受斯鲁利单抗联合化疗，C组接受安慰剂联合化疗。

数据截至2025年8月7日，三组中位随访时间分别为48.4个月、45.4个月和45.7个月。 A、B、C组中位OS分别为23.7个月（95% CI：20.5–27.5）、26.8个月（95% CI：21.2–30.9）和20.3个月（95% CI：16.2–24.6）。结果显示，斯鲁利单抗联合化疗方案对比单纯化疗治疗显著提升生存获益。与C组（化疗组）相比，B组（斯鲁利单抗联合化疗）死亡风险显著降低（HR=0.66，95% CI：0.52–0.83，P<0.001）。试验中C组79例患者（37.6%）进展后交叉接受斯鲁利单抗联合HLX04治疗，交叉换药会稀释免疫方案真实生存优势。经两阶段模型校正消除交叉干扰后，C组校正后中位OS降至14.2个月（95% CI：11.9–17.0），B组相较校正后对照组（C组）获益进一步放大（HR=0.53，95% CI：0.42–0.68，P<0.001）。采用RPSFTM模型进行校正后，C组中位OS为16.4个月（95% CI：13.2–19.4），B组相较C组的校正后HR为0.62（95% CI：0.49–0.80，P<0.001）。三药联合（A组）相比两药免疫联合（B组）未能展现出额外的生存获益。长期生存终点显示，B组48个月的OS率达34.0%，而化疗组（C组）仅16.2% 的患者存活超4年，有力夯实斯鲁利单抗联合化疗为患者带来持久长期生存的循证证据。

研究主要终点无进展生存期（PFS）方面，此前该研究的中期PFS结果已在2025年世界肺癌大会（WCLC）上以口头报告形式首次发布，并同期发表于《柳叶刀·呼吸医学》（The Lancet Respiratory Medicine）。本次最终分析更新的PFS数据显示，斯鲁利单抗联合化疗组（B组）中位PFS为11.0个月，显著优于化疗组（C组）的5.7个月，疾病进展风险下降46%。在肿瘤缓解方面，B组确认的客观缓解率（ORR）为52.8%，中位缓解持续时间（DoR）长达15.4个月，对比 C 组 ORR 27.6%、中位 DoR 8.3 个月，两项疗效指标均显著改善。各亚组分析显示获益趋势一致，其中PD-L1 TPS≥50%的患者及伴脑转移者均表现出明确的生存获益趋势。上述结果表明，斯鲁利单抗联合化疗在驱动基因阴性晚期nsqNSCLC患者中具有广泛的适用性，为该人群一线治疗提供了有效选择。

不一样的PD-1，从机制突破到全球可及

H药是复宏汉霖自主研发的创新型人源化抗PD-1单抗，具有差异化的药理机制。临床前研究证明，该药物不仅具备更强的PD-1内吞作用，可减少T细胞表面PD-1受体¹，实现快速、强效的免疫激活；还能减少PD-1对共刺激分子CD28的募集，从而更大程度保留CD28信号传导^2-4，增强下游AKT蛋白活性⁵，促进T细胞持续活化。依托独特的机制优势，H药在肺癌和消化道肿瘤领域均取得突破，是全球首个获批用于SCLC一线治疗的抗PD-1单抗，也是全球首个且唯一*获批胃癌围术期适应症的抗PD-1单抗。截至目前，H药已在全球范围内**获批鳞状非小细胞肺癌（sqNSCLC）、ES-SCLC、食管鳞癌（ESCC）和非鳞状非小细胞肺癌（nsqNSCLC）的一线治疗以及胃癌围术期治疗。

在肺癌治疗领域，H药已全面布局晚期一线治疗。基于ASTRUM-002研究的扎实数据，2024年，nsqNSCLC率先在中国获批上市，2026年5月，欧盟委员会亦正式批准其用于驱动基因阴性晚期nsqNSCLC的一线治疗，成为H药在欧盟获批的第三项一线肿瘤适应症。除已获批适应症之外，H药联合化疗及同步放疗一线治疗局限期小细胞肺癌（LS-SCLC）的国际多中心Ⅲ期研究已完成患者入组，在美国和日本同步开展的ES-SCLC桥接试验亦已全部完成入组。此外，多项研究者发起的研究（IIT）正持续拓展H药在NSCLC中的应用边界，将治疗时机前移至围术期阶段，积极探索其在更早期肺癌患者中的治疗潜力。消化道肿瘤方面，H药联合贝伐珠单抗及化疗一线治疗转移性结直肠癌（mCRC）的Ⅲ期国际多中心临床研究（ASTRUM-015）已完成全球入组，有望填补免疫治疗在MSS mCRC领域的临床空白。

在全球商业化层面，H 药已在全球 50 个国家和地区获批上市。自2025年2月H药首次获得欧盟批准以来，复宏汉霖携手欧洲区域合作伙伴Accord持续推进其市场准入与商业化落地。截至目前，H药已在16个欧洲国家实现上市销售，并在英国、奥地利、丹麦、德国、爱尔兰、意大利、西班牙和瑞典等10余个国家纳入医保或公共支付体系，进入当地主流医疗保障体系，持续提升长期用药可及性。

*截至2026年7月6日

**不同国家或地区的获批适应症请以当地药品监管部门发布的公告为准

关于复宏汉霖

复宏汉霖（2696.HK）是一家国际化创新生物制药企业，致力于为全球患者提供高品质、可负担的生物药，产品覆盖肿瘤、自身免疫疾病、眼科疾病等领域。自2010年成立以来，公司已构建涵盖全球研发、临床、注册、生产及商业化的全产业链平台，拥有全球员工近4,000人，并在中国、美国和日本等多地设有运营及分支机构。依托生物类似药形成的稳健现金流反哺创新研发，复宏汉霖正稳步迈入“全球化2.0”阶段，持续打造可复制、可持续的全球增长模式。截至目前，公司共有10款产品在全球60余个国家和地区获批上市，其中8款已在中国获批。在欧美主流生物药市场，复宏汉霖亦取得多项里程碑式突破，已有4款产品获得美国FDA批准、5款产品获得欧盟EC批准，充分体现了公司在研发体系、质量管理及生产能力方面已全面对标国际最高标准。

在创新驱动方面，复宏汉霖依托上海、美国等多地协同布局的研发体系，构建了多元化、平台化的创新技术矩阵，覆盖免疫检查点抑制剂、免疫细胞衔接器（包括多特异性TCE）、抗体偶联药物（ADC）以及AI驱动的早期研发平台等前沿方向。目前，公司拥有50余项处于早期阶段的创新资产，其中约70%具备同类最佳（Best-in-Class）潜力，并在全球同步推进30余项临床研究。核心产品H药汉斯状^®（斯鲁利单抗，欧洲商品名：Hetronifly^®）作为全球首个获批一线治疗小细胞肺癌和首个获批胃癌围术期适应症的抗PD-1单抗，正加速全球布局，已在全球50个市场获批上市；同时，多款潜力创新资产，包括PD-L1 ADC HLX43及新表位HER2单抗HLX22（通用名：dulpatatug）正全面推进全球关键性临床研究。依托通过中、欧、美三地GMP认证的生产体系，复宏汉霖已建成总产能达84,000升的生物药生产平台，形成覆盖全球六大洲的稳定供应网络。未来，复宏汉霖将始终坚持以患者为中心，聚焦未满足的临床需求，持续推动创新成果向临床价值与患者可及转化，在全球生物医药创新生态中创造长期而稳健的价值。

Henlius’ Serplulimab Final Analysis in nsqNSCLC Published in Cancer Communications, Reinforcing Durable Survival Benefit

Recently, the final survival analysis of the Phase 3 ASTRUM-002 study involving serplulimab, Henlius’ self-developed anti-PD-1 monoclonal antibody (mAb), as first-line treatment for advanced non-squamous non-small cell lung cancer (nsqNSCLC), was formally published in the leading international oncology journal Cancer Communications (impact factor: 28.4). The study showed that serplulimab plus chemotherapy achieved a median overall survival (mOS) of 26.8 months. These findings had previously been presented as a Late-Breaking Abstract (LBA) at the 2025 European Society for Medical Oncology (ESMO) Congress. Publication in a prestigious peer-reviewed journal further strengthened the evidence supporting serplulimab plus chemotherapy as a first-line treatment option for patients with driver gene-negative advanced nsqNSCLC.

Nearly 4 Years of Follow-up OS Data Confirm Long-Term Survival Benefit

ASTRUM-002 is a three-arm, randomized, double-blind, multicenter phase 3 study designed to evaluate the survival benefit of serplulimab plus chemotherapy with or without HLX04 (bevacizumab) as first-line treatment in patients with driver gene-negative advanced non-squamous NSCLC. A total of 636 patients with treatment-naïve, locally advanced or metastatic nsq-NSCLC without epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK)/ROS proto-oncogene 1 receptor tyrosine kinase (ROS1) genetic alterations were randomized 1:1:1 to receive serplulimab plus HLX04 and chemotherapy (group A), serplulimab plus HLX04 placebo and chemotherapy (group B), or double placebo plus chemotherapy (group C).

As of August 7, 2025, the median follow-up durations were 48.4 months, 45.4 months, and 45.7 months in groups A, B, and C, respectively. Median OS was 23.7 months (95% confidence interval [CI]: 20.5–27.5), 26.8 months (95% CI: 21.2–30.9), and 20.3 months (95% CI: 16.2–24.6) in group A, B, and C, respectively. The results demonstrated that serplulimab plus chemotherapy significantly improved survival outcomes compared with chemotherapy alone. Compared with group C (chemotherapy alone), group B (serplulimab plus chemotherapy) significantly reduced the risk of death by 34% (hazard ratio [HR]=0.66, 95% CI: 0.52–0.83, P<0.001). A total of 79 (37.6%) patients in group C had crossed over to serplulimab plus HLX04 treatment, which may have diluted the true survival benefit of the immunotherapy-based regimen. Median OS in group C adjusted by the 2-stage model was 14.2 months (95% CI 11.9 to 17.0), and the survival benefit of group B versus the adjusted group C was further amplified (HR=0.53, 95% CI: 0.42–0.68, P<0.001). Median OS in group C adjusted for crossing over and subsequent immunotherapy using the RPSFTM model was 16.4 (95% CI: 13.2–19.4) months, resulting in an adjusted HR of 0.62 (95% CI: 0.49–0.80; P < 0.001) for group B compared to group C. No statistical difference in median OS for group A compared to group B. Long-term survival outcomes further showed that the 48-month OS rate reached 34.0% in group B, compared with only 16.2% in group C, providing strong evidence that serplulimab plus chemotherapy can confer durable and long-term survival benefit for patients.

Regarding progression-free survival (PFS), the interim PFS results from ASTRUM-002 were previously presented as an oral presentation at the 2025 World Conference on Lung Cancer (WCLC) and published simultaneously in The Lancet Respiratory Medicine. In this final analysis, updated PFS data showed that median PFS in group B was 11.0 months, significantly superior to 5.7 months in group C, corresponding to a 46% reduction in the risk of disease progression. In terms of tumor response, the confirmed objective response rate (ORR) in group B was 52.8%, with a median duration of response (DoR) of 15.4 months. By comparison, group C achieved an ORR of 27.6% and a median DoR of 8.3 months, indicating marked improvements in both efficacy outcomes.

Subgroup analyses showed a consistent trend of survival benefit across various patient populations. Notably, patients with PD-L1 TPS ≥50% and those with brain metastases both demonstrated clear trends toward an improved median PFS and mOS. These findings suggest that serplulimab plus chemotherapy has broad applicability and offers as an effective first-line treatment option in patients with driver gene-negative advanced nsqNSCLC.

A Differentiated PD-1: From Mechanistic Innovation to Global Accessibility

As an innovative anti-PD-1 mAb independently developed by Henlius, serplulimab is distinguished by a differentiated mechanism. Preclinical studies have proven that serplulimab not only induces stronger PD-1 internalization—reducing PD-1 receptor presence on T cells for rapid and potent immune activation¹—but also minimizes PD-1-mediated recruitment of the co-stimulatory molecule CD28, thereby preserving CD28 signaling,^2-4 enhancing downstream AKT activity,⁵ and promoting sustained T-cell activation. Leveraging its unique mechanistic advantages, serplulimab has achieved breakthroughs in both lung cancer and gastrointestinal cancer. It is the world’s first anti-PD-1 mAb approved for first-line treatment of SCLC, and also the first and only* anti-PD-1 mAb approved for the perioperative treatment of gastric cancer. To date, serplulimab has been approved globally** for first-line treatment of squamous non-small cell lung cancer (sqNSCLC), ES-SCLC, esophageal squamous cell carcinoma (ESCC), and non-squamous non-small cell lung cancer (nsqNSCLC), as well as perioperative treatment of gastric cancer.

In the field of lung cancer, serplulimab has fully covered the first-line treatment of advanced lung cancer. Based on the robust data from ASTRUM-002, it was first approved in China in 2024 for nsqNSCLC. In May 2026, the European Commission also formally approved it for first-line treatment of driver gene-negative advanced nsqNSCLC, marking its third approved indication in the European Union. Beyond already approved indications, patient enrollment has been completed in an international multicenter Phase 3 trial evaluating serplulimab in combination with chemotherapy and concurrent radiotherapy as first-line treatment for limited-stage SCLC (LS-SCLC). In addition, bridging studies for ES-SCLC being conducted in parallel in the United States and Japan have also completed enrollment. Meanwhile, multiple investigator-initiated trials (IITs) are continuing to expand the boundaries of serplulimab in NSCLC, moving treatment earlier into the perioperative setting and actively exploring its therapeutic potential in earlier-stage lung cancer. In gastrointestinal cancer, global enrollment has been completed in the international multicenter Phase 3 study ASTRUM-015, which is evaluating serplulimab in combination with bevacizumab and chemotherapy as first-line treatment for metastatic colorectal cancer (mCRC), with the potential to address an unmet need for immunotherapy in patients with MSS mCRC.

At the commercial level, serplulimab has been approved in 50 countries and regions worldwide. Since receiving its first approval in the European Union in February 2025, Henlius has been working closely with its regional partner Accord to advance market access and commercialization across Europe. To date, serplulimab has been commercially launched in 16 European countries and has been included in reimbursement or public healthcare coverage systems in over 10 countries, including the UK, Austria, Denmark, Germany, Ireland, Italy, Spain, and Sweden, continuing to improve long-term treatment accessibility for patients.

About Henlius

Shanghai Henlius Biotech, Inc. (2696.HK) is a global, innovation-driven biopharmaceutical company committed to delivering high-quality, affordable biologic therapies to patients worldwide. The Company focuses on major disease areas including oncology, autoimmune diseases, and ophthalmic diseases. Founded in 2010, Henlius has established an integrated, end-to-end biopharmaceutical platform encompassing global R&D, clinical operations, regulatory affairs, manufacturing, and commercialisation. The Company employs nearly 4,000 people globally and operates across multiple regions, including China, the United States, and Japan. Leveraging the stable cash flow generated from its biosimilar portfolio to support innovation, Henlius is steadily advancing into its “Globalisation 2.0” phase, building a scalable and sustainable global growth model. Up to date, Henlius has achieved regulatory approvals for 10 products across over 60 countries and regions worldwide, including eight approvals in China. The Company has also reached multiple milestones in major biopharmaceutical markets, with four products approved by the U.S. Food and Drug Administration (FDA) and five products approved by the European Commission (EC), reflecting its globally aligned R&D capabilities, quality systems, and manufacturing standards.

Driven by innovation, Henlius has built a diversified, platform-based technology ecosystem through coordinated R&D efforts across Shanghai, the United States, and other regions. Its innovation platforms span immune checkpoint inhibitors, immune cell engager technologies (including multispecific T cell engagers), antibody-drug conjugates (ADCs), and AI-enabled early discovery platforms. The Company currently has more than 50 early-stage innovative assets, approximately 70% of which are expected to be best-in-class, with over 30 clinical trials ongoing globally. Henlius’ core product, serplulimab (trade name: Hetronifly^® in Europe), is the world’s first anti–PD-1 mAb approved for first-line treatment of small cell lung cancer and for perioperative gastric cancer. Up to date, it has been approved in 50 markets worldwide with an accelerated globalisation process. In parallel, multiple high-potential innovative assets—including the PD-L1 ADC HLX43 and the novel epitope anti-HER2 mAb dulpatatug (HLX22) — are advancing through global pivotal clinical development. Supported by a biologics manufacturing network with a total capacity of 84,000L and GMP certifications from regulatory authorities in China, Europe, and the United States, Henlius has established a stable global supply system serving six continents. Guided by a patient-centred mission, Henlius remains focused on addressing unmet medical needs and translating scientific innovation into meaningful clinical value and patient access, contributing sustainably to the global biopharmaceutical ecosystem.

To learn more about Henlius, visit https://www.henlius.com/en/index.html and connect with us on LinkedIn at https://www.linkedin.com/company/henlius/.

参考文献

References

1. Issafras H, et al. Structural basis of HLX10 PD-1 receptor recognition, a promising anti-PD-1 antibody clinical candidate for cancer immunotherapy. PLoS One. 2021;16(12):e0257972.

2. Hui E, et al. T cell costimulatory receptor CD28 is a primary target for PD-1-mediated inhibition. Science. 2017;355(6332):1428-1433.

3. Patsoukis N, et al. Interaction of SHP-2 SH2 domains with PD-1 ITSM induces PD-1 dimerization and SHP-2 activation. Commun Biol. 2020;3(1):128.

4. Fenwick C, et al. Tumor suppression of novel anti-PD-1 antibodies mediated through CD28 costimulatory pathway. J Exp Med. 2019;216(7):1525-1541.

5. Primavera E, et al. Computer-Aided Identification of Kinase-Targeted Small Molecules for Cancer: A Review on AKT Protein. Pharmaceuticals (Basel). 2023;16(7):993.

联系方式

媒体：PR@Henlius.com

投资者：IR@Henlius.com