A Single-arm, Open-label, Phase II Study to Evaluate Clinical Efficacy, Safety and Pharmacokinetics of HLX10 (Recombinant Humanized Anti-PD-1 Monoclonal Antibody Injection) in Combination with Chemotherapy (Carboplatin-Etoposide) in Previously Untreated Japanese Patients with Extensive Stage Small Cell Lung Cancer (ES-SCLC)

Evaluate Clinical Efficacy, Safety and Pharmacokinetics of HLX10 (Recombinant Humanized Anti-PD-1 Monoclonal Antibody Injection) in Combination with Chemotherapy (Carboplatin-Etoposide) in Previously Untreated Japanese Patients with Extensive Stage Small Cell Lung Cancer (ES-SCLC)

开始日期2025-03-31

申办/合作机构

上海复宏汉霖生物技术股份有限公司

NCT06850103

/ Not yet recruiting临床2期IIT

A Phase II Exploratory Multicenter Randomized Controlled Clinical Trial to Evaluate the Effectiveness of Neoadjuvant Short-Course Radiotherapy (SCRT) Followed by CAPEOX Chemotherapy and Serplulimab in Microsatellite Stable (MSS) or Proficient Mismatch Repair (pMMR) Rectal Cancer With Synchronous Oligometastases

Background and Significance:
Colorectal cancer (CRC) ranks as the third most common cancer and the second leading cause of cancer-related deaths globally. Despite improved early screening rates, a significant proportion of newly diagnosed CRC patients present with synchronous metastases, predominantly liver metastases. The concept of oligometastases, introduced by Hellman and Weichselbaum in 1995, describes a transitional state between localized disease and widespread metastases, characterized by limited metastatic lesions (typically 1-5) confined to 1-2 organs.
Current Treatment Landscape:
The management of oligometastatic disease combines local therapeutic approaches (surgery, radiotherapy, radiofrequency ablation) with systemic treatments, aiming to achieve No Evidence of Disease (NED) status. The ESMO guidelines officially categorized metastatic CRC into oligometastatic and widespread metastatic states in 2016, emphasizing the importance of integrated local and systemic treatments for oligometastatic colorectal liver metastases (CRLM).
Treatment Evolution and Challenges:
While the EPOC study established CAPEOX neoadjuvant chemotherapy followed by R0 resection as the standard treatment for initially resectable CRLM, patients with synchronous rectal cancer oligometastases present unique challenges due to complex local anatomy and high local recurrence risks. Although various neoadjuvant approaches, including Total Neoadjuvant Therapy (TNT), have been studied, they have not demonstrated significant long-term survival benefits, primarily because distant metastases impact survival more significantly than local recurrence.
Innovative Approach:
Recent success with Immunotherapy-Based Total Neoadjuvant Therapy (iTNT) in microsatellite stable/proficient mismatch repair (MSS/pMMR) locally advanced rectal cancer has shown promising results. Short-course radiotherapy (SCRT) combined with chemotherapy and immunotherapy has demonstrated superior efficacy trends, attributed to radiation's immune-activating effects on both local and distant tumor microenvironments.
Research Objective:
This project aims to evaluate the effectiveness of iTNT combined with SCRT in MSS/pMMR rectal cancer patients with synchronous oligometastases. The novel approach integrates SCRT with CAPEOX chemotherapy and Serplulimab, potentially improving complete response rates, organ preservation opportunities, and overall treatment efficacy while reducing recurrence risks. This pioneering study represents the first investigation of iTNT in synchronous rectal cancer oligometastases, offering a potentially transformative treatment strategy for this challenging patient population.
Research Innovation:
The study uniquely combines SCRT, CAPEOX chemotherapy, and Serplulimab in a neoadjuvant setting for MSS/pMMR synchronous rectal cancer oligometastases, addressing an unmet clinical need and potentially establishing a new treatment paradigm in this field.

开始日期2025-03-28

申办/合作机构

浙江大学医学院附属第一医院（浙江省第一医院）

CTR20250349

/ Recruiting临床1/2期

一项评估HLX43（抗PD-L1 的ADC）联合斯鲁利单抗（抗PD-1人源化单克隆抗体注射液）在晚期/转移性实体瘤患者中的安全性、耐受性和有效性的Ib/II 期临床研究

Ib期（剂量递增阶段）：主要目的：评价HLX43 联合斯鲁利单抗在晚期/转移性实体瘤患者中的安全性和耐受性，确定联合用药中HLX43 的最大耐受剂量（MTD）。次要目的：研究HLX43 的药代动力学（PK）特征及斯鲁利单抗的血药浓度；研究HLX43 及斯鲁利单抗的免疫原性；研究HLX43 联合斯鲁利单抗的潜在疗效；研究HLX43 联合斯鲁利单抗治疗晚期/转移性实体瘤患者的潜在药效学、潜在预测性和耐药性生物标志物。 II 期（剂量拓展阶段）：主要目的：研究不同剂量HLX43 联合斯鲁利单抗治疗晚期非小细胞肺癌（NSCLC）的有效性。次要目的：研究HLX43 联合斯鲁利单抗治疗晚期NSCLC 的安全性和耐受性，确定后续临床试验推荐剂量（RP2/3D）；研究HLX43 在NSCLC 患者体内的PK 特征；研究HLX43 免疫原性；研究HLX43 联合斯鲁利单抗治疗NSCLC 的潜在药效学、潜在预测性和耐药性生物标志物。

开始日期2025-03-05

申办/合作机构

上海复宏汉霖生物技术股份有限公司

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100 项与斯鲁利单抗相关的临床结果

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100 项与斯鲁利单抗相关的转化医学

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100 项与斯鲁利单抗相关的专利（医药）

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项与斯鲁利单抗相关的文献（医药）

2025-12-31·ANNALS OF MEDICINE

Cost-effectiveness of PD-1 inhibitors combined with chemotherapy for first-line treatment of oesophageal squamous cell carcinoma in China: a comprehensive analysis

Article

作者: Zhang, Lingli ; Xu, Kai ; Yu, Man ; Lin, Yingtao ; Li, Xin ; Su, Dan ; Shang, Jingjing ; Sun, Qingli ; Gong, Jinhong ; Qian, Xiaodan

BACKGROUND:

Programmed death-1 (PD-1) inhibitors combined with chemotherapy have become a standard first-line treatment for advanced oesophageal squamous cell carcinoma (ESCC). Given the high costs associated with immunotherapy, evaluating the cost-effectiveness of different PD-1 inhibitors in the Chinese healthcare setting is essential for guiding treatment decisions and policy development.

METHODS:

A cost-effectiveness analysis was conducted comparing six PD-1 inhibitors-sintilimab, toripalimab, tislelizumab, camrelizumab, serplulimab, and pembrolizumab-combined with chemotherapy for first-line treatment of advanced ESCC. A partitioned survival model was used to calculate incremental cost-effectiveness ratios (ICERs) from healthcare system perspective, with a willingness-to-pay (WTP) threshold set at $36,598.19 per quality-adjusted life year (QALY). Sensitivity analyses were performed to evaluate the robustness of the results.

RESULTS:

The ICERs for toripalimab, camrelizumab, pembrolizumab, serplulimab, sintilimab, and tislelizumab were $32,356.79/QALY, $48,410.64/QALY, $312,743.54/QALY, $121,200.84/QALY, $29,663.42/QALY, and $35,304.33/QALY, respectively. Sintilimab, toripalimab, and tislelizumab were below the WTP threshold. Among all regimens, the top three in life years (LYs) gained were toripalimab, serplulimab, and tislelizumab. Sensitivity analysis showed that utility values and drug prices were key factors influencing ICERs. Probabilistic analysis indicated that toripalimab, sintilimab, and tislelizumab had the highest probabilities of being cost-effective, at 83.1%, 81.4%, and 70.0%, respectively.

CONCLUSION:

Sintilimab, toripalimab, and tislelizumab are the most cost-effective PD-1 inhibitors when combined with chemotherapy for the first-line treatment of advanced ESCC in China, with ICERs below the WTP threshold. While all six PD-1 inhibitors demonstrated clinical benefits, pembrolizumab and serplulimab were less favourable from a cost-effectiveness standpoint. Sensitivity analysis confirmed that drug prices and utility values are significant determinants of cost-effectiveness.

2025-02-01·INTERNATIONAL IMMUNOPHARMACOLOGY

Deep analysis of the trials and major challenges in the first-line treatment for patients with extensive-stage small cell lung cancer

Review

作者: Yin, Xiaoyan ; Zhuang, Lulu ; Wu, Peizhu ; Gao, Ran ; Meng, Xiangjiao

The median overall survival (OS) is approximately 10 months when chemotherapy alone is the first-line treatment for extensive-stage small cell lung cancer (ES-SCLC). The approval of the two PD-L1 inhibitors, atezolizumab and durvalumab, marked the beginning of the immunotherapy era for ES-SCLC. Serplulimab, as the first PD-1 inhibitor to achieve success in the first-line treatment of ES-SCLC, has not only demonstrated significant improvements in patient survival outcomes but also ushered in a new era for PD-1 inhibitors in the treatment of ES-SCLC. Recently, antiangiogenic agents with chemo-immunotherapy have achieved breakthroughs in first-line ES-SCLC treatment. Improving the clinical benefits of individualized treatment for patients with ES-SCLC remains challenging. Challenges include identifying biomarkers for targeted therapy, exploring new treatments, developing new medicines, and classifying SCLC molecular subtypes. This review provides an in-depth analysis of research on first-line ES-SCLC treatment. Additionally, it discusses advances in ES-SCLC treatment.

2025-01-01·BIOMEDICINE & PHARMACOTHERAPY

Combined treatment of small cell lung cancer using radiotherapy and immunotherapy: Challenges and updates

Review

作者: Cao, Zhumin ; Tian, Ke ; Wang, Bin ; Jiang, Jinxiu ; Deng, Kai

Currently, chemotherapy remains the standard first- and second-line treatment for small cell lung cancer (SCLC). Research concerning immunotherapy has brought about a remarkable development in the treatment pattern of SCLC. Atirizumab, duvalizumab, atezolizumab, and serplulimab can significantly improve the clinical outcomes of SCLC. Given the rapidly evolving concept that combining immunotherapy with radiotherapy can increase therapeutic effectiveness, clinicians are devoted to further improving local tumor control by integrating immunotherapy with radiotherapy. This paper reviews the research progress in this field to date and explores ways to further enhance the efficacy of this combination therapy. We first discussed that immunotherapy combined with radiotherapy can improve the abscopal effect, progression-free survival, and overall survival rates of SCLC patients. Then, the biomarkers related to the radiation immune microenvironment, such as programmed death ligand-1 (PD-L1), tumor mutational burden (TMB), and the immune function of patients were discussed. Next, we explored the occurrence and underlying mechanisms of immune resistance during radiotherapy implementation. Finally, we clarified that the emerging trend of low-dose radiotherapy help overcome the inhibitory signals that limit T-cell infiltration in the tumor matrix. In summary, considering the rapid development of this field, these combined therapy strategies may have unlimited potential to further improve the efficacy of radiotherapy combined with immunotherapy for patients.

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项与斯鲁利单抗相关的新闻（医药）

2025-04-09

·BiG生物创新社

复宏汉霖斯鲁利单抗附条件批准是“捷径”还是“坑”？

作者｜大道至简2022年3月，复宏汉霖的PD-1抑制剂斯鲁利单抗（Serplulimab，汉斯状®，或H药）获得国家药品监督管理局（NMPA）附条件批准上市，用于不可切除或转移性微卫星高度不稳定（MSI-H）的成人晚期实体瘤患者，成为国内第七款上市的抗PD-1单抗。此后，该药的其他适应症又陆续获批，包括鳞状非小细胞肺癌（sqNSCLC）、广泛期小细胞肺癌（ES-SCLC）和晚期、复发或转移性食管鳞状细胞癌（ESCC），以及2024年12月批准的第五项适应症非鳞状非小细胞肺癌（nsNSCLC）。 01 附条件批准和适应症选择根据公开资料，斯鲁利单抗2022年首次附条件批准的这项适应症为微卫星高度不稳定（MSI-H）实体瘤，后续的适应症，如鳞状非小细胞肺癌、广泛期小细胞肺癌、食管鳞癌等则是通过常规审评程序获批。全球斯鲁利单抗获批适应症一览表来源：自NMPA、FDA、EMA和企业官网整理为什么附条件批准选择了微卫星高度不稳定（MSI-H）实体瘤呢？我们先来回顾一下附条件批准相关的制度。2020年11月，国家药监局发布了《药品附条件批准上市技术指导原则（试行）》，目的是鼓励以临床价值为导向的药物创新，加快具有突出临床价值的临床急需药品上市。（1）适用情形严重危及生命且尚无有效治疗手段的疾病（如晚期恶性肿瘤等）；国家卫生健康部门认定的公共卫生急需药品；重大突发公共卫生事件（I/II级）急需的疫苗或治疗药物。（2）准入条件需证明药物在有效性、安全性或依从性上显著优于现有疗法，例如：改善疾病预后；适用于现有疗法无效或不耐受患者；降低不良反应或提升治疗依从性。（3）有效性评价的替代路径对于符合附条件批准情形的药品，可基于替代终点、中间临床终点或早期临床试验数据而附条件批准上市。申请人应充分评估说明所选择的替代路径与预期的临床获益之间的相关性、合理性，并提供相应的证据。替代终点（如肿瘤缩小率）：需证明与临床获益（如生存率）的合理相关性。中间临床终点（如缩短临床试验周期）：需验证短期数据对长期疗效的预测能力。早期临床试验数据：如重大疫情中，疫苗的期中分析数据或中药人用经验数据可作为支持依据。（4）补充条款2023年8月25日，国家药监局综合司发布《药品附条件批准上市申请审评审批工作程序（试行）（修订稿征求意见稿）》，在领域药品批准口径方面做出调整。政策规定，某药品获附条件批准上市后，原则上不再同意其他同机制、同靶点、同适应症的同类药品开展相似的以附条件上市为目标的临床试验申请。也就是说，为避免同质化竞争，CDE要求附条件批准的新适应症需具备差异化优势，同类药品仅允许一家“先到先得”。根据上述政策，进一步推测CDE选择在治疗微卫星高度不稳定（MSI-H）实体瘤上附条件批准斯鲁利单抗的原因：（1）弥补国内短板早在2017年，美国食品药品监督管理局（FDA）就加速批准了帕博利珠单抗（Keytruda®）用于微卫星高度不稳定（MSI-H）实体瘤治疗，但中国直到2021年才有首款针对该适应症的抗PD-1单抗恩沃利单抗上市。斯鲁利单抗的出现进一步弥补了国内的短板，尤其是在标准治疗失败或无满意替代治疗方案的情况下，为国内患者提供了新的治疗选择和希望。（2）早期临床数据支持斯鲁利单抗在针对微卫星高度不稳定（MSI-H）实体瘤的临床试验中表现出良好的疗效和安全性。一项斯鲁利单抗治疗微卫星高度不稳定（MSI-H）实体瘤的关键II期单臂研究（HLX10-010-MSI201）数据显示，客观缓解率（ORR）31.0%，疾病控制率（DCR）54.8%，6 个月和 12 个月缓解持续时间（DoR）率均为 82.5%。此外，⼤多数不良事件的发⽣率与已上市的PD-1类研究结果相似。（3）免疫应答率高，适用癌种广泛微卫星高度不稳定（MSI-H）通常与错配修复缺陷（dMMR）相关，这类肿瘤患者对免疫检查点抑制剂（如抗PD-1/PD-L1单抗）具有较高的应答率。研究表明，MSI-H患者在使用免疫治疗时，尤其是抗PD-1/PD-L1单抗治疗时，能够显著提高生存率和缓解率。MSI-H状态在多种实体瘤中普遍存在，包括子宫内膜癌、结直肠癌、胃癌、肾细胞癌、卵巢癌等。这些癌症类型中，MSI-H的发生率约为14%。因此，斯鲁利单抗附条件批准的微卫星高度不稳定（MSI-H）实体瘤，适应症覆盖范围较广，能够满足多类癌种患者的需求。 02 新药附条件上市的风险与难度中国附条件批准政策允许基于早期临床数据（如II期单臂试验）加速审批，但需在限定时间内完成确证性临床试验。那么，结合斯鲁利单抗案例，看看新药附条件上市的风险与难度在哪里？（1）临床数据不确定性斯鲁利单抗2022年的这次获批，基于一项关键的单臂临床II期试验（HLX10-010-MSI201），患者均为单一中国本土患者，样本量较小，FAS人群仅42例，且未覆盖儿童患者，客观缓解率（ORR）为31%，低于帕博利珠单抗（Keytruda®）批准该适应症时的客观缓解率（ORR）39.6%（约40%）。斯鲁利单抗的这项II期临床研究也未明确完全缓解率（CR）的具体数据，长期生存数据（如中位总生存期OS）仍需更长时间随访。在安全性方面，斯鲁利单抗现有数据显示，接受治疗的患者中所有级别的不良反应发生率为92.8%，3级以上不良反应率高达41.9%，上市后真实世界使用可能暴露罕见不良反应。附条件批准后需持续追踪罕见或长期不良反应，例如免疫相关不良事件（irAE）的发生率可能随患者基数扩大而上升。FDA曾统计过去10年附条件批准的药物，有20%因安全性或疗效问题被撤销，抗肿瘤药占比达65%。（2）成本投入和竞争优势的平衡截至2024年12月，复宏汉霖对斯鲁利单抗累计研发投入达29.8亿元，附条件批准后仍需做临床Ⅲ期试验，高额投入对企业的资金管理能力构成挑战。同时，国内PD-1赛道竞争激烈，后续有更多用于该适应症的竞品被批，而且帕博利珠单抗（Keytruda®）在2023年已在国内批准用于该适应症，在临床使用时，医生可能更倾向于选择已有国际临床经验的成熟产品。（3）政策变化的风险2023年8月，国家药监局在《药品附条件批准上市申请审评审批工作程序（试行）（修订稿征求意见稿）》中提出：“明确附条件批准前就要开启确证性研究，并且要求4年内完成确证性研究。”就是说，若附条件批准的药物未能定期汇报、按时推进确证性临床试验、完成后续研究，药监部门可注销批准，亦可能导致药物直接退市。除此之外，斯鲁利单抗未来参与到医保谈判，降价压力也是复宏汉霖必须面对的考验。 03 对药企的启示与策略建议第一课：避开“内卷”，适应症选择差异化。注重差异化布局，聚焦未满足临床需求，如罕见病或疗效空白领域。复宏汉霖没有盲目跟随跨国药企的研发路径，采用“小适应症快速上市+大适应症逐步拓展”模式。斯鲁利单抗以MSI-H泛癌种附条件获批后，再扩展至肺癌等大适应症，避开PD-1高竞争领域的红海。第二课：借船出海，分摊风险。通过授权合作，分散研发风险，提升商业化效率。复宏汉霖将斯鲁利单抗的欧洲和印度市场授权给印度公司Intas，东南亚市场通过KG Bio合作布局，在美国则是与Syneos共同开发，降低独自闯关的合规成本。目前，斯鲁利单抗已覆盖到了欧美、东南亚等70余个市场。第三课：擅用“组合拳”。研发管线协同，延长产品生命周期；快速推入市场，提升患者可及性。复宏汉霖探索“PD-1+化疗+靶向药”联合治疗方案，覆盖更多癌种，延长产品生命周期。2022年正值疫情期间，斯鲁利单抗在附条件批准后仅过去4个工作日，全国10多家顶级医院就开出首张处方，足见企业具备强大的医院覆盖能力和快速的市场推进力。目前，斯鲁利单抗已完成中国境内全部省份的招标挂网，覆盖全国约1800家约36000名专业医生。作为复宏汉霖的第一个创新药产品，斯鲁利单抗在2024年贡献销售额13.09亿元，较上年同期增长约为1.89亿元，涨幅16.9%，已经成为复宏汉霖业绩的重要支撑。结语斯鲁利单抗的附条件批准与后续适应症拓展，既展现了中国监管机构对创新药的审慎态度，也为药企创新提供了战略启示。目前，斯鲁利单抗的附条件批准中已删除/注销了“既往经过氟尿嘧啶类、奥沙利铂和伊立替康治疗后出现疾病进展的晚期结直肠癌患者；既往至少二线治疗后出现疾病进展且无满意替代治疗方案的晚期胃癌患者；既往至少一线治疗后出现疾病进展且无满意替代治疗方案的其他晚期实体瘤患者”，原因可能是验证性研究数据不足，或是针对这些患者的临床获益有限、副作用发生率较高，又或是企业对研发策略和产品定位的调整，将适应症扩展到泛癌种生物标志物导向治疗而非特定癌种，避免在一些已广泛适用的领域直接竞争，将资源集中于更具潜力的方向。总之，附条件批准上市并非产品的终点，而是风险与机遇并存的起点。正如复宏汉霖秉持一贯秉持的理念“以患者为中心”，企业需以临床价值为核心，在科学创新与合规风险间找到平衡，通过差异化设计、全球化布局和高效资源整合，推动真正满足未竟医疗需求的产品，在全球竞争中占据一席之地。参考资料1.Yang G, Zheng RY, Jin ZS.Correlations between microsatellite instability and the biological behaviour of tumours. J Cancer Res Clin Oncol. 2019 Dec;145(12):2891-2899.2.斯鲁利单抗注射液.上海复宏汉霖生物制药有限公司.2022年3月.3.官网或其他公开资料.共建Biomedical创新生态圈！如何加入BiG会员？

临床研究上市批准疫苗

2025-04-09

·复宏汉霖

复宏汉霖PD-L1 ADC HLX43联合H药汉斯状® Ib/II临床研究招募晚期/转移性实体瘤受试者

临床招募由上海复宏汉霖发起的“一项评估HLX43（抗PD-L1的ADC）联合斯鲁利单抗（抗PD-1人源化单克隆抗体注射液）在晚期/转移性实体瘤患者中的安全性、耐受性和有效性的Ib/II期临床研究”正在招募受试者。HLX43是靶向PD-L1的新型抗体偶联药物，临床前研究及I期临床研究提示，HLX43在抗PD-1/PD-L1单抗耐药的非小细胞肺癌等多个瘤种中显示出显著疗效，且耐受性良好。临床前及临床研究结果表明ADC和PD-1/L1 单克隆抗体联合用药可产生协同增效作用。该项临床试验已在多家研究中心获得伦理批准。申办方上海复宏汉霖生物技术股份有限公司上海复宏汉霖生物医药有限公司如果您符合以下入选标准您将有可能加入这项临床试验年龄18-75周岁；经组织学或细胞学确认的，经标准治疗失败或无标准治疗的晚期/转移恶性实体肿瘤患者根据RECIST 1.1疗效评价标准，至少具有一个可测量病灶；您将获得HLX43产品和斯鲁利单抗静脉输注治疗；研究规定的影像学检查、12导联心电图检查、实验室检查（包括血常规、血生化、凝血、内分泌功能检查等）等；研究治疗期间，研究医生为您做疾病诊断和治疗指导注：本临床试验遵守《药物临床试验质量管理规范》和《赫尔辛基宣言》。目前正在开展的研究中心清单中心名称主要研究者联系人联系方式陆军军医大学第二附属医院朱波敖老师15683231863山东省肿瘤医院孙玉萍陈老师18854063652河南科技大学第一附属医院张治业王老师19103798705湖南省肿瘤医院邬麟余老师腾老师1320312134319330097253上海市胸科医院钟华关老师13611739100吉林省肿瘤医院程颖俞老师13147749193华中科技大学同济医学院附属同济医院褚倩黄老师15871718698郑州大学第一附属医院黄思远孙老师18848893038哈尔滨医科大学附属肿瘤医院于雁张老师17614663816中国人民解放军陆军特色医学中心（大坪医院）李力陈老师18875157579天津市肿瘤医院陈鹏秦老师15832112368南方医科大学珠江医院魏婷李老师18078191702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，4款产品在国际获批上市，5个上市申请分别获中国药监局、美国FDA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，涵盖约50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）、全球首个获批一线治疗小细胞肺癌的抗PD-1单抗汉斯状®（斯鲁利单抗，欧洲商品名：Hetronifly®）以及汉奈佳®（奈拉替尼）。公司亦同步就19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。喜欢本文内容点击下方按钮·分享 ·收藏 ·点赞 ·在看

抗体药物偶联物上市批准临床1期申请上市

2025-04-09

·复宏汉霖

复宏汉霖 PD-L1 ADC HLX43联合H药汉斯状®的Ib/II临床研究完成首例受试者给药

2025年4月9日，复宏汉霖（2696.HK）宣布，公司基于与宜联生物的合作开发的靶向程序性死亡-配体1（PD-L1）的新型抗体偶联药物（ADC）注射用HLX43联合自研的H药汉斯状®（抗PD-1人源化单克隆抗体注射液，通用名：斯鲁利单抗注射液）用于治疗晚期/转移性实体瘤患者的Ib/II期临床试验（HLX43HLX10-ST201）于中国完成首例受试者给药。此前，HLX43单药或联合治疗晚期/转移性实体瘤已在中国启动II期临床研究并完成首例受试者给药。目前，全球尚无同类靶向PD-L1的ADC产品获批上市，仅有SGN-PDL1V（来自辉瑞）计划于2025年下半年启动临床III期试验，HLX43为全球第二款也是国内首款进入临床阶段的靶向PD-L1的ADC产品。近年来，以抗PD-1/L1抗体为代表的免疫检查点抑制剂（ICI）促进了肿瘤免疫治疗的高速发展，成为肿瘤患者各线治疗的主要手段之一。然而，部分患者对该疗法无响应，或者出现耐药[1]。对于免疫治疗耐药或经免疫治疗等标准治疗失败后的患者人群，尚缺少有效的后线治疗方案，亟待探索更前沿的新型治疗方案，进一步提高患者的临床获益。ADC作为当下肿瘤治疗中疗效最突出的新型疗法，已在乳腺癌、肺癌、食管癌、胃癌等多项实体瘤中展现出初步的治疗潜力，成为重要的探索方向[2]。而PD-L1在非小细胞肺癌、结直肠癌、三阴性乳腺癌、鳞状细胞癌等多种癌种中均有表达，且在正常组织中的表达有限，使其成为开发ADC药物的潜力靶点，为肿瘤治疗带来新的途径[3]。HLX43兼具抗体分子的高度靶向性和细胞毒素的强大杀伤力，可通过与肿瘤细胞表面PD-L1 抗原特异性结合，经内吞后释放小分子毒素，从而发挥抗肿瘤作用。其采用的毒素DNA拓扑异构酶I（Topoisomerase I）抑制剂在血液中的半衰期更短，安全性更好，同时其更强的膜穿透性和细胞膜亲和力便于产品发挥旁观者效应[4]，独特的作用机制使得HLX43较同类ADC产品具有更大的治疗窗口，增强ADC在实体肿瘤中的治疗效果。临床前研究及I期临床研究提示，HLX43在抗PD-1/PD-L1单抗耐药的非小细胞肺癌等多个瘤种中显示出显著疗效，且耐受性良好，临床前研究数据于2023欧洲肿瘤内科学会（ESMO）大会以壁报形式进行展示。基于此，公司于近期启动了HLX43在食管鳞癌等潜在实体瘤适应症中的II期临床试验，以进一步评HLX43的疗效和安全性。在加速拓展抗体偶联药物（ADC）产品布局的同时，复宏汉霖亦积极探索ADC与免疫治疗药物的联用方案，前瞻性布局IO+ADC治疗领域，以期实现协同增效的抗肿瘤疗效，进一步提高患者的临床获益，解决未满足的临床需求。未来，复宏汉霖将持续立足于未满足的临床需求，充分发挥公司在抗体药物和抗体偶联药物领域的一体化平台优势，加速推动更多前沿治疗方案的研究和开发，为全球患者带来更多高质量、可负担的创新治疗方案。关于HLX43HLX10-ST201本研究为一项旨在评估HLX43联合汉斯状®治疗晚期/转移性实体瘤患者的安全性、耐受性和有效性的Ib/II期临床研究。研究分为Ib期剂量递增和II期剂量拓展两个阶段。第一阶段为开放标签研究，合格的受试者将接受不同剂量的HLX43联合固定剂量的汉斯状®静脉输注给药，每3周一次（Q3W）。第二阶段为多中心、随机、开放标签的对照研究，在第一阶段数据的基础上，评估3个不同剂量的HLX43联合固定剂量汉斯状®在晚期非小细胞肺癌（NSCLC）患者中的安全性和有效性。第一阶段的主要终点为剂量限制性毒性（DLT）观察期内每个剂量组发生DLT事件的受试者比例和HLX43联合汉斯状®用药的最大耐受剂量（MTD）。第二阶段的主要终点为独立影像评估委员会（IRRC）根据实体瘤疗效评价标准（RECIST）v1.1评估的客观缓解率（ORR）。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，4款产品在国际获批上市，5个上市申请分别获中国药监局、美国FDA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，涵盖约50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）、全球首个获批一线治疗小细胞肺癌的抗PD-1单抗汉斯状®（斯鲁利单抗，欧洲商品名：Hetronifly®）以及汉奈佳®（奈拉替尼）。公司亦同步就19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。First Subject Dosed for a Phase 1b/2 Clinical Trial of Henlius' PD-L1-Targeting ADC HLX43 in Combination with Novel Anti-PD-1 mAb SerplulimabShanghai, China, April 9, 2025 — Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first subject has been dosed for a phase 1b/2 clinical trial of HLX43 for Injection, the novel Programmed Death-Ligand 1 (PD-L1)-targeting antibody-drug conjugate (ADC) that developed by the company based on the collaboration with MediLink Therapeutics, in combination with the Henlius' independently developed innovative anti-PD-1 monoclonal antibody (mAb) HANSIZHUANG (serplulimab injection), for the treatment of patients with advanced/metastatic solid tumours in Chinese mainland. Recently, the company has also completed the first subject dosing for a phase 2 clinical trial of HLX43 for monotherapy or combination therapy to treat patients with advanced/metastatic solid tumours. At present, no PD-L1 targeting ADC has been approved for marketing globally, and only SGN-PDL1V from Pfizer is about to initiate a phase 3 clinical trial. HLX43 is the world's second and China's first PD-L1-targeting ADC to progress to clinical research.Immune checkpoint inhibitors represented by PD-1/PD-L1 monoclonal antibodies have emerged in recent years and revolutionised all lines of treatment for tumour patients. However, there are still many patients with positive PD-L1 expression who do not respond to or develop resistance to PD-1/PD-L1-targeted therapy [1]. To date, there has been no subsequent-line treatment for patients who are resistant to PD-1/L1 immunotherapy or failed to benefit from the standard treatments including immunotherapy, indicating a significant unmet medical need to further improve the clinical benefits for these patients. As a novel targeting therapy with the most prominent anti-tumour efficacy, ADCs have shown preliminary therapeutic potential in the treatment of multiple advanced solid tumours, such as breast cancer (BC), lung cancer (LC), esophageal cancer (EC) and gastric cancer (GC), making it a promising therapeutic in solid tumours [2]. PD-L1 is expressed in patients across a broad spectrum of tumour types including non-small cell lung cancer (NSCLC), colorectal cancer (CRC), triple negative breast cancer (TNBC), squamous cell carcinoma and displays limited expression on normal tissues, highlighting the potential of PD-L1 as a target for ADCs, which may bring new options for cancer treatment [3].Combining the selectivity of targeted monoclonal antibodies with the highly potent cytotoxic agent, HLX43 could exert anti-tumour effects through specific binding to the PD-L1 expressed on the surface of tumour cells and release cytotoxic payloads after internalisation by the cancer cells. The cytotoxic payload of HLX43 is a novel DNA topoisomerase-I inhibitor which are known for their potent anti-tumor activity, shorter half-life in the bloodstream, and improved safety profile [4]. This next generation design allows HLX43 to possess a higher therapeutic index and potency for treatment of solid tumours. Several non-clinical studies and the phase 1 clinical trial have shown that, HLX43 has good anti-tumour effects and a favorable tolerability profile in non-small cell lung cancer (NSCLC), and other tumour types that were PD-1/L1 mAb-resistant. The results of the pre-clinical studies were published as poster presentation at the 2023 European Society of Medical Oncology (ESMO) Congress. Based on these compelling results, Henlius has initiated phase 2 clinical trials of HLX43 in potential solid tumour indications including ESCC 安定other solid tumours to further evaluate the efficacy and safety of HLX43. While accelerating the development of ADCs and diversified drug conjugates, Henlius is also actively exploring combination therapies involving ADCs with immunotherapy to encourage progress in the next wave innovation of “IO+ADC”, further providing more effective treatment options to fulfill the unmet clinical needs.Moving forward, Henlius remains committed to addressing unmet medical needs by leveraging its antibody drug R&D platform, actively driving the development of innovative therapies to deliver high-quality and affordable treatment options to patients worldwide.About HLX43HLX10-ST201This phase 1b/2 study aims to evaluate the safety, tolerability, and efficacy of HLX43 in combination with HANSIZHUANG in patients with advanced/metastatic solid tumors. The study is divided into two stages: phase 1b dose escalation and phase 2 dose expansion. Eligible subjects will receive intravenous infusions of different doses of HLX43 combined with a fixed dose of HANSIZHUANG every three weeks (Q3W). The second stage is a multicenter, randomized, open-label controlled study to evaluate the safety and efficacy of three different doses of HLX43 combined with a fixed dose of HANSIZHUANG in patients with advanced non-small cell lung cancer (NSCLC) based on data from the first stage. The primary endpoints of the first stage are the proportion of subjects experiencing dose-limiting toxicity (DLT) events in each dose group during the DLT observation period and the maximum tolerated dose (MTD) of HLX43 in combination with HANSIZHUANG. The primary endpoint of the second stage is the objective response rate (ORR) assessed by the Independent Radiological Review Committee (IRRC) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.About HenliusHenlius (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, 4 have been approved for marketing in overseas markets, and 5 marketing applications have been accepted for review in China, the U.S. 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 about 50 molecules and has continued to explore immuno-oncology combination therapies with proprietary HANSIZHUANG (anti-PD-1 mAb) as the backbone. To date, the company's launched products include 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), HANSIZHUANG (serplulimab, trade name: Hetronifly® in Europe), the world’s first anti-PD-1 mAb for the first-line treatment of SCLC, and HANNAIJIA (neratinib). What’s more, Henlius has conducted over 30 clinical studies for 19 products, expanding its presence in major markets as well as emerging markets.References[1] Attili I, et al. Strategies to overcome resistance to immune checkpoint blockade in lung cancer[J]. Lung cancer: Journal of the International Association for the Study of Lung Cancer, 2021(154-):154.[2] He J, Zeng X, Wang C, Wang E, Li Y. Antibody-drug conjugates in cancer therapy: mechanisms and clinical studies. MedComm (2020). 2024 Jul 28;5(8):e671.[3] Kwan B, et al. 783 SGN-PDL1V, a novel, investigational PD-L1-directed antibody-drug conjugate for the treatment of solid tumors[J]. 2021.[4] Conilh, L, et al. Payload diversification: a key step in the development of antibody–drug conjugates. J Hematol Oncol 16, 3 (2023).联系方式媒体：PR@Henlius.com投资者：IR@Henlius.com喜欢本文内容点击下方按钮·分享 ·收藏 ·点赞 ·在看

抗体药物偶联物免疫疗法临床3期临床2期临床结果

100 项与斯鲁利单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	斯鲁利单抗	-	-

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
非鳞状非小细胞肺癌	中国	上海复宏汉霖生物制药有限公司	2024-12-01
食管鳞状细胞癌	中国	上海复宏汉霖生物制药有限公司	2023-09-19
广泛期小细胞肺癌	中国	上海复宏汉霖生物制药有限公司	2023-01-16
鳞状非小细胞肺癌	中国	上海复宏汉霖生物制药有限公司	2022-10-25
晚期胃癌	中国	上海复宏汉霖生物制药有限公司	2022-03-22
结直肠癌	中国	上海复宏汉霖生物制药有限公司	2022-03-22
MSI-H 实体瘤	中国	上海复宏汉霖生物制药有限公司	2022-03-22

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
食管癌	申请上市	中国	上海复宏汉霖生物制药有限公司	2022-08-26
MSI 癌症	申请上市	中国	上海复宏汉霖生物技术股份有限公司	2021-04-23
胃癌	临床3期	中国	上海复星医药产业发展有限公司	2023-01-30
晚期宫颈癌	临床3期	中国	上海复宏汉霖生物技术股份有限公司	2022-09-30
局限期小细胞肺癌	临床3期	美国	上海复宏汉霖生物技术股份有限公司	2022-05-17
局限期小细胞肺癌	临床3期	中国	上海复宏汉霖生物技术股份有限公司	2022-05-17
局限期小细胞肺癌	临床3期	奥地利	上海复宏汉霖生物技术股份有限公司	2022-05-17
局限期小细胞肺癌	临床3期	捷克	上海复宏汉霖生物技术股份有限公司	2022-05-17
局限期小细胞肺癌	临床3期	德国	上海复宏汉霖生物技术股份有限公司	2022-05-17
局限期小细胞肺癌	临床3期	希腊	上海复宏汉霖生物技术股份有限公司	2022-05-17

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临床结果

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ESMO_TAT2025	N/A	小细胞肺癌	39	Serplulimab plus chemotherapy	壓餘築遞網蓋願襯積選(壓製獵膚餘鬱壓鹽選夢) = 繭繭選鑰壓鬱憲網繭獵廠遞淵襯積製選憲糧構 (獵襯艱壓築獵選願鹹齋, 3.1 ~ 7.2) 更多	积极	2025-03-03
				Second-line serplulimab plus chemotherapy	壓餘築遞網蓋願襯積選(壓製獵膚餘鬱壓鹽選夢) = 餘鹽簾選鹽膚壓構鑰鬱廠遞淵襯積製選憲糧構 (獵襯艱壓築獵選願鹹齋, 6.9 ~ NR)
NCT05831891 (ASCO_GU2025) 人工标引	临床2期	肾细胞癌一线	16	Fruquintinib+serplulimab	構願糧淵醖壓構襯窪繭(獵鏇遞糧糧餘觸構鑰蓋) = not reached 鬱觸壓衊選憲顧構繭鑰 (繭廠餘襯願網遞衊築鏇 ) 更多	积极	2025-02-13
NCT04547166 (ASCO_GI2025) 人工标引	临床2/3期	转移性结直肠癌一线 Microsatellite Stable (MSS) \| PD-L1	112	Serplulimab + Bevacizumab + XELOX	夢廠構簾鏇衊鏇遞窪艱(網夢範選窪窪餘襯齋積) = 鬱衊糧願淵築選醖觸衊衊淵鏇窪積網鑰範顧衊 (廠遞夢積蓋齋蓋夢蓋鏇 ) 更多	积极	2025-01-23
				Placebo + Bevacizumab + XELOX	夢廠構簾鏇衊鏇遞窪艱(網夢範選窪窪餘襯齋積) = 糧構廠築蓋鏇獵選遞鹽衊淵鏇窪積網鑰範顧衊 (廠遞夢積蓋齋蓋夢蓋鏇 ) 更多
NCT03973112 (Pubmed \| Cancer Immunol Immunother) 人工标引	临床2期	晚期肝细胞癌一线	61	Serplulimab 3 mg/kg + HLX04HLX04 10 mg/kg	糧簾簾範鑰築繭鑰糧構(憲憲醖淵膚選膚淵積醖) = 獵糧餘構蓋獵醖醖蓋餘範壓繭鑰膚積觸膚網膚 (簾製範廠繭窪餘鬱壓遞, 18.1 ~ 42.7) 更多	积极	2025-01-03
ESMO_IO2024 人工标引	N/A	广泛期小细胞肺癌三线 \| 二线 \| 一线	40	Serplulimab + Chemotherapy + Anlotinib (first-line)	淵餘觸膚襯夢願膚鹹襯(繭網範繭艱簾鬱顧願簾) = 積醖窪選齋鏇願範遞鬱獵餘糧繭簾壓觸繭構廠 (膚鬱顧鑰願糧觸鬱鑰簾, 15.6 ~ NR) 更多	积极	2024-12-12
NCT05659251 (ESMO_IO2024) 人工标引	临床2期	食管鳞状细胞癌新辅助	48	Serplulimab + Chemotherapy	窪蓋壓獵餘廠醖齋淵願(艱鏇齋觸獵簾鬱淵淵獵) = 壓築膚積鹽構窪襯艱繭淵醖窪醖築鬱餘憲廠製 (糧願襯齋積廠範鏇夢壓 ) 更多	积极	2024-12-12
NEWS 人工标引	临床2期	肾细胞癌一线	16	斯鲁利单抗+呋喹替尼	憲齋艱廠繭淵糧艱艱獵(淵築選選構遞廠衊願餘) = 觸廠淵襯餘鬱觸顧廠襯鹽蓋蓋鑰窪襯膚廠繭選 (繭蓋繭簾淵繭壓膚廠築 ) 更多	积极	2024-12-09
ASTRUM-004R (ESMO_ASIA2024) 人工标引	N/A	鳞状非小细胞肺癌一线	100	Serplulimab plus Paclitaxel	夢遞鑰鑰憲鏇窪艱壓鑰(觸選艱艱鹽觸顧鹽製齋) = 鏇獵鹽壓夢選範窪廠齋蓋網製網憲壓窪艱鏇壓 (襯憲餘遞廠夢構範膚網 ) 更多	积极	2024-12-07
				Serplulimab plus Nab-paclitaxel	夢遞鑰鑰憲鏇窪艱壓鑰(觸選艱艱鹽觸顧鹽製齋) = 鏇壓餘製鏇鑰餘選膚鬱蓋網製網憲壓窪艱鏇壓 (襯憲餘遞廠夢構範膚網 ) 更多
NCT04033354 (ASTRUM-004, NEWS) 人工标引	临床3期	鳞状非小细胞肺癌一线	359	斯鲁利单抗+化疗	願鑰夢積顧齋製範醖糧(積膚製鹹選製衊膚憲憲) = 鑰廠鹹願蓋襯齋憲鹹顧夢壓衊淵遞築築壓鏇糧 (觸範構窪糧鹽醖顧觸壓 ) 更多	积极	2024-09-29
				安慰剂+化疗	願鑰夢積顧齋製範醖糧(積膚製鹹選製衊膚憲憲) = 繭齋構夢憲觸夢築獵廠夢壓衊淵遞築築壓鏇糧 (觸範構窪糧鹽醖顧觸壓 ) 更多
NCT04033354 (ASTRUM-004, ESMO2024) 人工标引	临床3期	鳞状非小细胞肺癌一线	309	Serplulimab plus chemotherapy	蓋艱鏇願鹹繭製願積壓(糧醖壓壓艱簾蓋醖夢鏇) = 壓鏇艱膚夢願餘願顧壓鑰齋構鬱鏇觸淵艱鹽憲 (範淵襯齋壓齋衊蓋鏇蓋 ) 更多	积极	2024-09-15
				Placebo plus chemotherapy	蓋艱鏇願鹹繭製願積壓(糧醖壓壓艱簾蓋醖夢鏇) = 範遞餘範襯鏇願網夢艱鑰齋構鬱鏇觸淵艱鹽憲 (範淵襯齋壓齋衊蓋鏇蓋 ) 更多