NRG-GY037: A Phase III Study of Induction Pembrolizumab and Chemotherapy Followed by Chemoradiation and Pembrolizumab Versus Chemoradiation and Pembrolizumab Both Followed by Pembrolizumab for High Risk Locally Advanced Cervical Cancer

This phase III trial compares the addition of induction chemotherapy, with carboplatin, paclitaxel and pembrolizumab, to chemotherapy and radiation, with cisplatin and pembrolizumab followed by pembrolizumab maintenance for the treatment of patients with cervical cancer that has spread to nearby tissue or lymph nodes (locally advanced). Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. Adding induction chemotherapy to the usual treatment of chemotherapy and radiation followed by maintenance may be more effective in treating patients with high risk, locally advanced cervical cancer.

开始日期2026-06-26

申办/合作机构

National Cancer Institute

NCT07061964

/ Recruiting临床2期IIT

Single Arm Phase II Study of Bladder Preservation With Immunoradiotherapy After a Clinically Meaningful Response to Neoadjuvant Therapy in Patients With Muscle Invasive Bladder Cancer (BRIGHT)

This phase II trial tests the effect of giving pembrolizumab in combination with radiation therapy after chemotherapy in preventing surgery to remove the bladder in patients with muscle invasive bladder cancer. Standard of care therapy includes chemotherapy before surgery (neoadjuvant) to shrink or get rid of the tumor. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Photon beam radiation therapy is a type of radiation therapy that uses x-rays or gamma rays that come from a special machine called a linear accelerator. The radiation dose is delivered at the surface of the body and goes into the tumor and through the body. Giving pembrolizumab in combination with radiation therapy after neoadjuvant chemotherapy may help prevent surgical removal of the bladder in patients with muscle invasive bladder cancer.

开始日期2026-06-01

申办/合作机构

National Cancer Institute

NCT07037004

/ Not yet recruiting临床2期IIT

Impact of Microbiome Modulation With CBM588 in Combination With Pembrolizumab for Adjuvant Therapy of High-Risk, Resected Renal Cell Carcinoma (RCC)

This phase II trial compares the effect of adding a Live Biotherapeutic Product called CBM588 to pembrolizumab versus pembrolizumab alone in preventing return of disease (recurrence) after surgery for patients with renal cell cancer. Pembrolizumab is an immune checkpoint inhibitor. Immunotherapy with monoclonal antibodies such as pembrolizumab may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Pembrolizumab is approved for the treatment of renal cell cancer after surgery. Research has shown that changes to the composition of the healthy bacteria in the body (the microbiome), may improve a patient's response to treatment with immunotherapy. CBM588, a Live Biotherapeutic Product (LBP) containing a bacteria called Clostridium butyricum, has been shown to improve outcomes in patients treated with immunotherapy for other types of cancer. Adding CBM588 to treatment with pembrolizumab after surgery may cause changes in the microbiome that improve patient response to treatment and reduce disease recurrence, compared to pembrolizumab alone.

开始日期2026-05-04

申办/合作机构

City of Hope National Medical Center

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100 项与帕博利珠单抗相关的临床结果

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100 项与帕博利珠单抗相关的转化医学

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100 项与帕博利珠单抗相关的专利（医药）

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10,375

项与帕博利珠单抗相关的文献（医药）

2026-02-01·COMPUTATIONAL BIOLOGY AND CHEMISTRY

Targeting colorectal cancer liver metastasis through repurposing metabolic and immune inhibitors: A theoretical study

Article

作者: Lahiri, Aditya ; Datta, Aniruddha ; Mondal, Madhurima

Liver metastasis from colorectal cancer is a major cause of death in patients with advanced colorectal cancer (CRC) and remains a difficult challenge in oncology. In spite of commendable developments in medical inventions, the complexity and poor prognosis of metastatic stage, alliterative strategies are required to address Colorectal cancer liver metastasis (CRLM). This paper presents a computational study on drug repurposing for CRLM using a Boolean Network model. We comprehensively analyze CRLM signaling pathways such as WNT, PI3K/AKT/mTOR, MAPK, Hedgehog, TGF-β, NF-kB, NOTCH and HGF and target them with metabolic and immune inhibitors. This study utilizes a computational analysis to evaluate single and multi-agent treatments across scenarios involving single and multiple genetic mutations. Our findings highlights the efficacy of metabolic inhibitors such as Simvastatin, Metformin, and predict compatible partner drugs to enhance their efficacy. Additionally, we predict possible improvements for CRLM treatment using an immunotherapy drug like Pembrolizumab. Overall, this paper suggests potential combinations requiring experimental validation for drug repurposing to improve CRLM treatment outcomes.

2026-01-01·TALANTA

Biosimilarity and advanced structural characterization of monoclonal antibodies charge variants using capillary zone electrophoresis and mass spectrometry

Article

作者: Joomun, Rania ; Gahoual, Rabah ; Alez-Martin, Lola ; François, Yannis-Nicolas ; Mignet, Nathalie ; Houzé, Pascal

Monoclonal antibodies (mAbs) structural complexity arises from their macromolecular nature and their propensity to undergo post-translational modifications (PTM), potentially leading to the formation of charge variants. Capillary zone electrophoresis (CZE) showed to be particularly relevant for their analysis, however the selectivity provided by CZE separation is not completely elucidated. In this work, CZE-UV analysis was used to characterize charge variants for biosimilars products corresponding to infliximab. Results demonstrated the possibility to identify faint variations between the different products showing its applicability to contribute to mAbs biosimilarity assessment. Enzymatic treatment allowed to attribute the origin of infliximab charge variants. CZE-UV analysis of pembrolizumab showed that none of the five charge variants separated were originating from C-terminal lysine residues and/or N-glycans. To enable further identification, an analytical strategy was developed to achieve CZE-UV fraction collection and enrichment of mAb charge variants followed by systematic offline characterization in CE coupled to tandem mass spectrometry (MS/MS). CE-MS/MS experiments allowed the identification of different types of PTMs such as N-terminal pyroglutamic acid formation and asparagine deamidation for charge variant fractions correlated with decreased mobility. In addition, for the first time succinimide intermediate formation could be successfully characterized using CE-MS/MS data, which could be correlated to increased mobility. Thus, the CZE-UV separation resulted from the synergistic effect of several simultaneous PTMs affecting the apparent mobilities of the charge variants. As a consequence, experiments illustrated the relevance and potential of intact mAbs analysis using CZE-UV to provide an overview of the structural diversity of therapeutic mAbs.

2026-01-01·JOURNAL OF PHARMACEUTICAL SCIENCES

Subcutaneously administered anti-PD-(L)1 antibodies are predominantly absorbed via the lymphatic system, resulting in high drug exposure to draining lymph nodes

Article

作者: Fei, Xiaoxuan ; Sun, Lie ; Yan, Simin ; Li, Li ; Zou, Jianjun ; Ge, Weihong ; Hu, Luojuan ; Han, Sifei ; Zhang, Huimin ; Pei, Junyi

Compared to classic intravenous (IV) administration, subcutaneous (SC) delivery of monoclonal antibodies (mAbs) offers new opportunities to improve patient compliance and healthcare efficiency. However, insufficient understanding of drug absorption process following SC administration, particularly the role of lymphatic transport, may hinder the development of SC formulations for mAbs. The current study aimed to examine the absorption route of widely used anti-PD-(L)1 mAbs following SC injection, and four marketed products (Pembrolizumab, Tislelizumab, Envafolimab, Sugemalimab) were selected as the model drugs. In the thoracic lymph duct-cannulated rat model, all mAbs were found to be primarily absorbed via the lymphatics following SC injection, with 63.1-72.0 % of the administered dose recovered in the thoracic lymph, contributing to >80 % of SC bioavailability. This absorption pattern also resulted in elevated exposure of mAbs in draining lymph nodes (an order of magnitude higher drug concentrations compared to the systemic drug exposure). In addition, markedly different lymphatic absorption profiles were observed following SC administration at different sites, reflecting specific draining routes associated with certain anatomical regions in the rat. Our data suggested that the food pad is likely the optimal SC injection site for quantitative studies of lymphatic transport, whereas injection to the lower hind leg (a common SC injection site in previous studies) appeared to underestimate the absolute extent of lymphatic drug transport in the thoracic lymph duct-cannulated rat model, as lymphatic drainage from this region partially bypasses the cannulation site, leading to incomplete collection of draining lymph.

9,525

项与帕博利珠单抗相关的新闻（医药）

19 小时之前

·投医问药

Cell丨范德堡大学利用大型语言模型生成抗原特异性双链抗体

点击蓝字关注我们投医问药 Summary 当前，传统抗体发现过程受限于效率低、成本高、成功率低等问题，且现有 AI 抗体制备方法多依赖初始抗体模板，无法实现无模板、抗原特异性抗体的高效设计，多种新兴病原体（如新型 H5N1 禽流感病毒）的抗体研发仍面临技术瓶颈，亟需突破现有方法局限的全新工具。 2025 年 11 月 4 日，美国范德堡大学医学中心 Ivelin S. Georgiev 团队（通讯作者）在《Cell》发表题为 “Generation of antigen-specific paired-chain antibodies using large language models”（利用大型语言模型生成抗原特异性双链抗体）的研究论文。研究团队开发了蛋白质语言模型 MAGE，通过整合公共数据库与 LIBRA-seq 数据构建训练集，对预训练模型 Progen2 进行微调，使其可针对目标抗原生成人源重链与轻链可变区双链抗体序列。实验验证表明，MAGE 生成的抗体对 SARS-CoV-2、H5N1、RSV-A 三种病原体均具有结合特异性，其中针对 SARS-CoV-2 的抗体中和效价优于 10 ng/mL，针对 H5N1 的抗体展现出零样本学习能力，且通过冷冻电镜解析证实抗体具有多样化结合模式。该模型无需初始模板即可设计多靶点抗体，为抗体研发提供了高效新方案。欢迎关注公众号并设置星标发送日期如20251105可获取原文 Highlights 模型功能明确：对蛋白质语言模型进行微调，使其具备生成抗原特异性抗体的能力数据集构建全面：整合公共数据库与 LIBRA-seq 数据，构建抗体 - 抗原序列数据库实验验证充分：在 RSV-A、SARS-CoV-2、H5N1 三种病原体上，验证了所设计抗体的功能抗体特性优异：生成的抗体具有多样化的结合特异性、中和活性及表位识别能力 01 ｜INTRODUCTION 人源单克隆抗体是一类多样化的治疗药物，理论上可特异性靶向任意蛋白质，因此成为治疗多种疾病的潜在候选药物。直至近年，抗体研发仍主要依赖基于发现的实验方法，通常需筛选接触过目标抗原的人或动物样本。尽管近年来抗体发现技术的通量已大幅提升，但该过程仍耗时费力、成本高昂。随着治疗性单克隆抗体市场规模持续扩大及应用场景不断拓展，对能加速抗体发现进程、拓展抗体研发能力的计算机工具需求日益迫切。人工智能领域的最新突破 —— 尤其是基于 Transformer 架构的大型语言模型（LLMs）和扩散模型在各类任务中展现出的卓越性能 —— 推动了抗体相关设计计算方法的快速发展。这些方法包括亲和力成熟、抗体重新设计及单域抗体制备等。然而，目前尚无已发表的方法能实现无模板、抗原特异性抗体的设计。现有方法局限于抗体重新设计，且聚焦于互补决定区（CDRs）的生成，需以初始抗体为模板提供抗体的可变基因及框架区。此外，这类模型多基于结构构建，训练过程需依赖抗体 - 抗原复合物，而由于数据不足（尤其是人源双链抗体数据），其应用范围受到极大限制。本研究中，研究团队提出 MAGE（单克隆抗体制备器）—— 一款蛋白质语言模型（PLM），可根据输入的抗原序列，生成具有结合特异性的重链与轻链可变区双链抗体序列。MAGE 通过对 Progen2（一款基于自回归解码器的大型语言模型，已在通用蛋白质序列上完成预训练）进行微调开发而成。Progen2 通过预测下一个氨基酸残基学习已知氨基酸序列，并利用自注意力机制捕捉输入序列中的复杂依赖关系。研究团队以该预训练模型对氨基酸序列的习得表征为基础，进一步学习人源抗体序列中与多种抗原靶点结合特异性相关的特征。研究表明，MAGE 生成的抗体序列具有多样化特征，包括重链与轻链可变基因的使用、体细胞超突变（SHM）水平，以及未在训练数据中出现的新型 CDR 序列。当以 SARS-CoV-2 野生型受体结合域（RBD）为提示时，经实验验证的 20 种 MAGE 生成抗体中，9 种被证实具有结合特异性，其中 1 种抗体对 SARS-CoV-2 的中和效价优于 10 ng/mL。研究团队还设计并验证了针对呼吸道合胞病毒 A（RSV-A）融合前 F 蛋白的抗体（23 种抗体中 7 种有效）—— 该靶点在训练数据中的占比显著较低。通过冷冻电镜（cryo-EM）解析了两种 MAGE 设计抗体与 RSV F 蛋白复合物的结构，证实 MAGE 生成的抗体具有多样化结合模式，且能在关键结合界面整合具有重要作用的残基。最后，MAGE 设计的抗体对 H5/TX/24 血凝素（HA）的结合能力也得到验证（18 种抗体中 5 种有效），展现出对训练数据中未出现的流感病毒株的零样本学习能力。因此，MAGE 是首个无需初始抗体序列模板即可设计针对目标抗原的新型人源功能抗体的模型。 02 ｜RESULTS 研究人员整合公共数据库（CoV-AbDab、SAbDab 等）与 LIBRA-seq 数据，构建含 18507 个抗体 - 抗原序列对的训练集，对 Progen2 模型进行微调，使其具备生成双链抗体的能力。通过对 1000 个针对 SARS-CoV-2 RBD 的生成抗体进行筛选，969 个序列符合 “无缺失 CDR / 框架区、长度达标、人源化评分≥70%” 标准；生成抗体使用 37 种重链可变基因与 30 种轻链可变基因，CDRH3 长度 5-28 aa、CDRL3 长度 7-12 aa，序列多样性显著；与训练数据对比，重链平均差异 11.7 个残基、轻链平均差异 1.4 个残基，且 CDR3 区域差异最大，证实序列新颖性。图1 Progen2 经微调用于抗原特异性抗体制备研究人员从 969 个符合标准的抗体中，按 “无偏筛选（10 种，覆盖前 5 种高频重链基因的 20% 与 80% germline 一致性序列）、偏倚筛选（10 种，含 5 种 CDRH3 高相似序列与 5 种重链高相似序列）” 原则，选择 20 种抗体进行实验验证。ELISA 结果显示，45%（9/20）的抗体与 SARS-CoV-2 RBD 结合（信号为背景 2 倍以上），其中无偏筛选的 RBD-839 结合信号与阳性对照 S309 相当；BLI 实验证实 8 种结合抗体对 RBD-SD1 的亲和力达纳摩尔至亚纳摩尔级，且对 RSV F 蛋白无交叉结合；结合抗体与训练数据的重链差异 5-25 个残基，即使差异达 18 个残基的 RBD-839 仍保持强结合能力，证实序列新颖性与功能有效性。图2 筛选 20 种抗体验证其与 RBD 的结合能力研究人员分析 9 种 RBD 结合抗体的序列特征，发现其 “公共性” 差异显著（RBD-61 无公共克隆，RBD-238 公共克隆超 100 个），且 8 种抗体的重链与训练数据的差异不仅限于 CDRH3 区域，证实 MAGE 可生成完整可变区新颖的抗体；6 种结合抗体可结合全长 SARS-CoV-2 刺突蛋白，部分还可交叉结合 SARS-CoV-1 与 Lyra-CoV 刺突蛋白；4 种抗体可中和 SARS-CoV-2 假病毒，其中 RBD-409 对野生型病毒的 IC₅₀达 6.7 ng/mL，对 Gamma、Delta 及多种 Omicron 亚型仍保持中和活性，展现出广谱抗病毒潜力。图3 生成的 RBD 结合抗体具有多样化序列特征研究人员分别以 RSV-A F 蛋白和 H5/TX/24 HA 蛋白为提示，各生成 1000 个抗体序列，发现针对特定抗原的生成序列中，对应抗原特异性克隆占比显著高于以 RBD 为提示的序列，证实模型可学习抗原特异性序列特征；三种抗原提示下的抗体重链可变基因使用存在显著偏好（RBD 提示偏好 IGHV3-53/66，RSV 提示偏好 IGHV1-18，H5 提示偏好 IGHV4-34），且 H5 与 RSV 提示生成的抗体与训练数据的差异更大（重链平均差异更高）、体细胞超突变（SHM）水平更高，序列新颖性更显著。图4 针对 RSV 与 H5/TX/24 的生成序列特征研究人员从 1000 个针对 H5/TX/24 HA 的生成抗体中，按与训练数据的 CDRH3 一致性分组，选择 18 种抗体验证，ELISA 结果显示 28%（5/18）的抗体强结合 H5/TX/24 HA，7 种弱结合；结合抗体的重链与训练数据差异 4-16 个残基、轻链差异 1-8 个残基，SHM 水平重链 6%-11%、轻链 7%-8%，且差异分布于整个重链区域，非仅 CDR 区；假病毒中和实验证实，5 种强结合抗体对 H5/TX/24 的 IC₅₀均 < 1 μg/mL，且对 H1、H5 等不同亚型流感病毒展现出多样化中和谱，证实其功能有效性与广谱性。图5 MAGE 生成针对 A/Texas/37/2024 H5 的新型结合抗体研究人员从 10000 个针对 RSV-A F 蛋白的生成抗体中，经筛选选择 23 种抗体验证，ELISA 结果显示 30%（7/23）的抗体可结合 RSV-A 融合前 F 蛋白，其中 3 种来自无偏筛选组；结合抗体的重链与训练数据差异 6-21 个残基、轻链差异 4-12 个残基，SHM 水平重链 3%-21%、轻链 2%-12%，且 7 种抗体的重链差异覆盖 4 个以上区域，序列新颖性显著；假病毒中和实验证实，3 种结合抗体可强效中和 RSV-A，其中无偏筛选的 RSV-2245（重链与训练数据差异 17 个残基，SHM 10%）中和活性最强，证实无模板设计的有效性。图6 MAGE 生成针对 RSV-A 的新型结合抗体研究人员通过冷冻电镜解析了 RSV-2245 与 RSV-3301 抗体 Fab 片段与 RSV-A F 蛋白复合物的 3.4 Å 分辨率结构，发现 RSV-2245 结合于融合前特异性抗原位点 V，通过重链 3 个 CDR 区与轻链 2 个 CDR 区形成疏水作用与氢键，其中 CDRH2 的 Tyr53 与 F 蛋白的 Tyr53 形成氢键，且轻链 CDRL1 的 Asp30（生殖系为 Asn）与 F 蛋白的 Lys192 形成盐桥（该突变在训练数据中仅占 0.34%）；RSV-3301 结合于抗原位点 I，主要依赖 CDRH3 的疏水作用与极性相互作用，CDRH1 的 Arg32 与 F 蛋白的 Glu378、CDRH2 的 Asp58 与 F 蛋白的 Lys390 形成盐桥；两种抗体结合模式完全不同，证实 MAGE 生成抗体的结合多样性。图7 RSV-2245 与 RSV-3301 抗体 Fab 片段结合 RSV-A F 蛋白的冷冻电镜结构 03 ｜DISCUSSION 本研究开发了纯序列依赖的 MAGE 模型，可根据抗原氨基酸序列生成重链 - 轻链双链抗体序列，无需模板抗体或蛋白质结构信息。经验证，MAGE 生成的抗体对 SARS-CoV-2 RBD、H5 HA、RSV-A F 蛋白均具有结合活性，部分抗体展现出强效中和能力；无偏筛选的抗体（如 RSV-2245）即使与训练数据差异显著，仍保持功能有效性；针对训练数据中未出现的 H5/TX/24 病毒株，MAGE 生成的抗体仍能有效结合并中和，展现出零样本学习能力。从序列特征看，MAGE 生成的抗体具有多样化的可变基因使用、CDR 长度及 SHM 水平，部分抗体的结合表位（如 RSV-3301 结合的位点 I）此前未被充分表征，且结构解析证实抗体可通过训练数据中罕见的突变（如 RSV-2245 的 Asp30）增强结合能力。研究还发现，MAGE 生成的抗体不仅能复现训练数据中的共识序列特征，还能产生与共识序列差异显著的功能抗体，且经 TAP 工具预测，这些抗体的可开发性符合临床阶段抗体标准。研究局限性包括：训练数据仅基于抗体 - 抗原结合的二元标注，未整合亲和力、中和活性等功能数据，因此无法定向生成高亲和力或强效中和抗体；模型目前仅针对病毒抗原验证，对细菌、肿瘤等其他抗原的适用性需进一步验证；大规模抗体表达与验证的技术挑战限制了低训练数据占比靶点的验证效率。未来通过整合更多功能数据、扩大训练集规模，MAGE 有望实现更广泛靶点的抗体设计。 References [1] Wasdin PT, Johnson NV, Janke AK, et al. Generation of antigen-specific paired-chain antibodies using large language models. Cell. 2025; 188: 1–16. https://doi.org/10.1016/j.cell.2025.10.006 [2] Hie BL, Shanker VR, Xu D, et al. Efficient evolution of human antibodies from general protein language models. Nature Biotechnology. 2024; 42: 275–283. [3] Desautels TA, Arrildt KT, Zemla AT, et al. Computationally restoring the potency of a clinical antibody against Omicron. Nature. 2024; 629: 878–885. [4] Rojas LA, Sethna Z, Soares KC, et al. Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer. Nature. 2023; 618: 144–150. [5] Weber JS, Carlino MS, Khattak A, et al. Individualised neoantigen therapy mRNA-4157 (V940) plus pembrolizumab versus pembrolizumab monotherapy in resected melanoma (KEYNOTE-942): a randomised, phase 2b study. Lancet. 2024; 403: 632–644. [6] Yarmarkovich M, Marshall QF, Warrington JM, et al. Targeting of intracellular oncoproteins with peptide-centric CARs. Nature. 2023; 623: 820–827. [7] Benton A, Liu J, Poussin MA, et al. Mutant KRAS peptide targeted CAR-T cells engineered for cancer therapy. Cancer Cell. 2025; https://doi.org/10.1016/j.ccell.2025.05.006 [8] Li G, Mahajan S, Ma S, et al. Splicing neoantigen discovery with SNAF reveals shared targets for cancer immunotherapy. Science Translational Medicine. 2024; 16: eade2886. [9] Nijkamp E, Ruffolo JA, Weinstein EN, et al. ProGen2: Exploring the boundaries of protein language models. Cell Systems. 2023; 14: 968–978.e3. [10] Abu-Shmais AA, Guo L, Khalil AM, et al. A potently neutralizing and protective human antibody targeting antigenic site V on RSV and hMPV fusion glycoprotein. bioRxiv. 2024; https://doi.org/10.1101/2024.10.31.621295 [11] Chen EC, Gilchuk P, Zost SJ, et al. Convergent antibody responses to the SARS-CoV-2 spike protein in convalescent and vaccinated individuals. Cell Reports. 2021; 36: 109604. 投医问药投医问药起源于清华大学、北京大学和中国科学院，包含投医问药分享会和投医问药俱乐部，以及与清华大学生命科学学院合办的行业大咖论坛等板块，为生物医药领域专业人士专门打造，通过小型圆桌论坛和分享会的形式，提供一个深度交流和合作的平台。俱乐部成员包括PI、博士后、博士生以及生物医药产业和金融界的专业人士。在这里，大家可以分享自己的研究成果，讨论科研转化的可能性，寻找合作伙伴和资本介入的机会。投医问药注重建立信任关系，保持公益性，为生物医药相关人士促成各类资源的精准匹配，促进科研成果、创业想法的转化和社会价值的实现。欢迎关注投医问药，并添加小编微信号：seekmedicine，添加微信时请备注：单位/职业/姓名，如果是PI/教授、创始人、合伙人等，还请注明。声明：本内容仅用作生物医药行业信息传播，不构成任何用药和投资建议。如需转载，请务必注明文章作者和来源。对本文有异议或投诉，请联系seekmedicine@163.com。点赞收藏分享

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就这么一款抗癌药，在短短的10年时间卖了1400亿美元，折合人民币将近1万亿元，有款叫帕博利珠单抗的抗癌药，那真是莫沙东公司的“摇钱树”。帕博利珠单抗作为一款PD-1免疫检查点抑制剂，已在全球获批超过30项适应症，从经一线治疗失败的转移性黑色素瘤，到EGFR基因突变阴性的局部晚期非小细胞肺癌，

就这么一款抗癌药，在短短的10年时间卖了1400亿美元，折合人民币将近1万亿元，有款叫帕博利珠单抗的抗癌药，那真是莫沙东公司的“摇钱树”。帕博利珠单抗作为一款PD-1免疫检查点抑制剂，已在全球获批超过30项适应症，从经一线治疗失败的转移性黑色素瘤，到EGFR基因突变阴性的局部晚期非小细胞肺癌，再到转移性食管鳞状细胞癌，为多种癌症患者提供了生存期延长的可能。这款2014年在美国获批、2018年进入中国的药物，不仅在临床上展现出实际价值，更在市场上创造了惊人成绩——截至2024年初，其上市近十年的累计销售额接近1400亿美元，2023年单年销售额达250.11亿美元，超越常年霸榜的修美乐成为全球“药王”，占默沙东当年药品收入的46.67%。同样的治疗方案在不同国家的价格差距显著。美国患者完成两年疗程需支付约20万美元，而中国市场同款疗程费用约14万元人民币。尽管中国定价远低于美国，但由于目前该药物尚未纳入医保，1.5万至1.875万元一支的采购价，仍构成不少患者的经济负担，这种差异直观反映出全球药品定价体系的复杂性。天价药费背后是制药行业的高风险研发逻辑。默沙东从2000年启动帕博利珠单抗的研发，耗时11年才推动其上市，单款药物投入约50亿美元。这并非个例：全球新药研发平均成本高达26亿美元，临床试验周期平均24个月，从二期临床推进到三期的成功率不足30%。默沙东2024年全球研发投入达179亿美元，这些资金中大部分最终会成为“沉默成本”——那些投入巨大却未能上市的项目，最终只能靠少数成功药物的利润覆盖。值得注意的是，默沙东的企业形象并非只有商业属性。1989年，在中国乙肝疫苗技术尚处空白阶段，该公司以极低价格转让基因重组乙肝疫苗技术，不仅邀请中国技术人员赴美学习，还捐赠设备、派遣工程师协助建起疫苗工厂。中国疾控中心原副主任梁晓峰曾感慨，这一举动让千万中国儿童免受乙肝病毒侵害，为社会节省了巨大成本。这款“药王”的专利将在2028年到期，届时本土企业可合法生产生物类似药，市场竞争将推动价格大幅下降。事实上，国内企业早已布局相关仿制工作：百奥泰曾推进帕博利珠单抗生物类似药研发，累计投入超2.24亿元，后因欧美药监政策调整——疗效比对研究不再是上市审批必要数据——终止部分临床试验以节省成本。德国、瑞士的药企也纷纷调整同类仿制项目的临床方案，为专利到期后的市场竞争做准备。参考过往案例，仿制药上市后价格通常降幅超35%，复旦张江的一款抗癌药就因集采调整价格，降幅达35%以上。帕博利珠单抗的故事折射出创新药的完整生命周期：从高额投入换来的临床突破，到专利保护期内的商业回报，再到专利到期后的普惠化。这背后是专利制度对创新的激励与对公众需求的平衡，也提出了深层命题——如何在保障企业研发动力的同时，让救命药更快抵达普通患者手中。这场关于科学、商业与民生的平衡，仍在持续探索中。

生物类似药临床3期疫苗带量采购

22 小时之前

·ETPharma

Merck secures $700 million funding from Blackstone to develop cancer therapy

Bengaluru: Merck said on Tuesday that it has entered into an agreement to receive funds managed by Blackstone Life Sciences for $700 million to develop an experimental cancer therapy. Under the terms of the agreement, Blackstone's drug development unit will fund a portion of the development costs to test sac-TMT , an experimental antibody-drug conjugate . Antibody-drug conjugates are designed to deliver an anti-cancer drug more precisely to malignant cells, causing less damage to healthy cells than chemotherapy. Merck is currently evaluating sac-TMT in 15 global late-stage trials spanning six tumor types, including breast, endometrial and lung cancers. The company is working on adding new drugs to its pipeline as its blockbuster cancer drug Keytruda faces competition from cheaper biosimilars later this decade. "We are making important investments...to sustain our business for the future, while remaining disciplined towards maintaining an appropriate financial profile," said Caroline Litchfield, chief financial officer, Merck. The payment is expected to be made throughout 2026, the companies said. Blackstone is eligible to receive low-to-mid single-digit royalties on net sales of sac-TMT, contingent upon receipt of regulatory approval in the U.S. Sac-TMT targets a protein called trophoblast cell-surface antigen 2, found on the surface of various cancer cells. Antibody-drug conjugates that target this protein have shown encouraging anti-tumor activity in clinical studies, Merck said. The company added that it will retain control over the development, manufacturing and commercialization of sac-TMT, and Blackstone will not receive any rights to the cancer therapy. Sac-TMT is being developed as part of an exclusive license and collaboration agreement with Sichuan Kelun-Biotech Biopharmaceutical. (Reporting by Sneha S K in Bengaluru; Editing by Vijay Kishore)

引进/卖出抗体药物偶联物

100 项与帕博利珠单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10574	帕博利珠单抗	L01XC18	DB09037

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
局部晚期头颈部鳞状细胞癌	冰岛	Merck Sharp & Dohme BV	2025-10-30
局部晚期头颈部鳞状细胞癌	列支敦士登	Merck Sharp & Dohme BV	2025-10-30
局部晚期头颈部鳞状细胞癌	挪威	Merck Sharp & Dohme BV	2025-10-30
不可切除的肝细胞癌	中国	Merck Sharp & Dohme LLC	2025-06-10
不可切除的胸膜恶性间皮瘤	冰岛	Merck Sharp & Dohme BV	2025-04-16
不可切除的胸膜恶性间皮瘤	挪威	Merck Sharp & Dohme BV	2025-04-16
不可切除的尿路上皮癌	欧盟	Merck Sharp & Dohme BV	2024-07-25
不可切除的尿路上皮癌	冰岛	Merck Sharp & Dohme BV	2024-07-25
不可切除的尿路上皮癌	列支敦士登	Merck Sharp & Dohme BV	2024-07-25
不可切除的尿路上皮癌	挪威	Merck Sharp & Dohme BV	2024-07-25
晚期子宫内膜癌	美国	Merck Sharp & Dohme LLC	2024-06-17
MSI-H 子宫内膜癌	美国	Merck Sharp & Dohme LLC	2024-06-17
错配修复缺陷子宫内膜癌	美国	Merck Sharp & Dohme LLC	2024-06-17
晚期胃癌	日本	MSD KK (Tokyo)	2024-05-17
复发性胃癌	日本	MSD KK (Tokyo)	2024-05-17
不能切除的胆道癌	加拿大	Merck Sharp & Dohme Corp.	2024-05-09
晚期胆道癌	中国	Merck Sharp & Dohme LLC	2024-01-30
局部晚期胆管癌	中国	Merck Sharp & Dohme LLC	2024-01-30
胃腺癌	挪威	Merck Sharp & Dohme BV	2023-12-20
HER2阴性胃癌	美国	Merck Sharp & Dohme LLC	2023-11-16

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
肌层浸润性膀胱癌	申请上市	美国	Merck & Co., Inc.	2025-10-23
复发性铂耐药性卵巢癌	申请上市	美国	Merck & Co., Inc.	2025-10-20
小肠癌	申请上市	欧盟	Merck Sharp & Dohme Corp.	2022-03-25
卵巢上皮癌	临床3期	美国	Merck Sharp & Dohme Corp.	2021-12-13
卵巢上皮癌	临床3期	日本	Merck Sharp & Dohme Corp.	2021-12-13
卵巢上皮癌	临床3期	比利时	Merck Sharp & Dohme Corp.	2021-12-13
卵巢上皮癌	临床3期	加拿大	Merck Sharp & Dohme Corp.	2021-12-13
卵巢上皮癌	临床3期	哥伦比亚	Merck Sharp & Dohme Corp.	2021-12-13
卵巢上皮癌	临床3期	丹麦	Merck Sharp & Dohme Corp.	2021-12-13
卵巢上皮癌	临床3期	德国	Merck Sharp & Dohme Corp.	2021-12-13

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临床结果

适应症

分期

评价

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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


NCT04370509 (CTgov)	临床2期	转移性肾细胞癌 \| 晚期肾细胞癌 \| 肾细胞癌 ... 更多	6	Cytoreductive Nephrectomy (CN)+Pembrolizumab	衊鹽鬱範鹹範醖鬱獵糧 = 糧鏇壓獵獵膚壓衊網廠鬱憲蓋顧壓襯餘鹹範顧 (襯襯蓋蓋衊廠艱窪鏇憲, 膚構憲製蓋鏇艱壓顧衊 ~ 遞蓋網築願範簾觸選壓) 更多	-	2025-11-05
NCT03069378 (CTgov)	临床2期	血管肉瘤	41	Pembrolizumab+T-Vec	獵選齋鏇範觸鹽廠遞餘 = 網廠顧網築繭壓糧齋憲夢衊網網鏇獵淵膚窪糧 (築餘襯積製齋選廠顧範, 願簾構構鬱願壓襯蓋製 ~ 顧積顧願積廠廠壓鹹膚) 更多	-	2025-10-29
NCT04828486 (CTgov)	临床2期	晚期肝细胞癌	14	Quality-of-Life Assessment+Futibatinib+Pembrolizumab	鑰艱憲積醖襯積窪獵廠 = 鹹獵繭願繭簾膚蓋淵獵願鹹憲繭製衊壓齋繭範 (構網衊衊鏇餘願製醖齋, 齋壓鹹顧襯淵糧淵選齋 ~ 糧鏇鏇廠廠簾糧鏇艱蓋) 更多	-	2025-10-29
NCT03728972 (CTgov)	临床2期	外周T细胞淋巴瘤 \| 结外NK-T细胞淋巴瘤 \| NK细胞淋巴瘤	19	Pembrolizumab (Early-Stage NK/T-cell Lymphoma/ENKTL (Stage I/II))	衊築夢簾窪糧觸鹽艱鹽 = 鹽範範衊鑰窪顧鑰醖繭鹽窪範廠鹽積繭築構淵 (襯淵鹽憲築鹹夢鏇淵衊, 鏇窪壓觸製獵蓋壓鏇觸 ~ 膚願築蓋餘獵蓋築鏇鏇) 更多	-	2025-10-23
				Pembrolizumab (Early-Stage NK/T-cell Lymphoma/ENKTL (Stage III/IV))	衊築夢簾窪糧觸鹽艱鹽 = 齋窪範鏇膚獵築選壓窪鹽窪範廠鹽積繭築構淵 (襯淵鹽憲築鹹夢鏇淵衊, 齋積鹹廠網繭願範鹹遞 ~ 鑰顧齋膚壓齋糧製艱壓) 更多
NCT03049618 (CTgov)	临床2期	复发性头颈癌 \| 非小细胞肺癌IIIA期 \| 复发性头颈部鳞状细胞癌 ... 更多	42	Laboratory Biomarker Analysis+Recombinant EphB4-HSA Fusion Protein+Pembrolizumab (Head and Neck Cancer Cohort)	齋觸鹽餘糧鑰構壓築夢 = 艱鑰製選簾顧夢鹽膚夢餘餘淵醖繭醖簾選構鬱 (壓醖獵壓鹹鑰醖鬱夢範, 蓋築範製築糧膚鹽鬱構 ~ 衊襯淵鹽壓憲選鹽鏇顧) 更多	-	2025-10-22
				Laboratory Biomarker Analysis+Recombinant EphB4-HSA Fusion Protein+Pembrolizumab (Non-Small Cell Lung Cancer Cohort)	齋觸鹽餘糧鑰構壓築夢 = 構觸衊艱構願衊艱醖選餘餘淵醖繭醖簾選構鬱 (壓醖獵壓鹹鑰醖鬱夢範, 憲遞鏇壓獵蓋遞鹹網鬱 ~ 糧蓋餘遞鬱壓繭網觸範) 更多
NCT03425643 (KEYNOTE-671, ESMO2025) 人工标引	临床3期	可切除非小细胞肺癌 \| 非小细胞肺癌新辅助	797	Pembrolizumab+chemoPembrolizumab	齋製糧醖鹹齋憲鬱鬱選(範膚齋艱鹹網憲齋範窪) = 繭蓋製簾襯鏇蓋醖繭鏇鏇艱鏇鑰蓋艱製鬱構鹹 (襯積簾餘衊醖鏇構鏇顧, 44.6 ~ 55.0) 更多	积极	2025-10-17
				Placebo+chemo	齋製糧醖鹹齋憲鬱鬱選(範膚齋艱鹹網憲齋範窪) = 鑰繭簾鏇遞襯窪齋鹹夢鏇艱鏇鑰蓋艱製鬱構鹹 (襯積簾餘衊醖鏇構鏇顧, 21.7 ~ 31.5) 更多
NCT03740165 (ENGOT-ov43, ESMO2025)	临床3期	一线	1,367	Pembro + ola	-	积极	2025-10-17
				Pembro + chemo
NCT05101629 (IKF t-037, ESMO2025)	临床2期	晚期肝细胞癌	32	Pembrolizumab 200 mg/Q3WLenvatinib 8-12 mg daily + Pembrolizumab 200 mg/Q3WLenvatinib 8-12 mg daily	簾獵壓艱願鬱願餘鏇膚(衊遞構構蓋夢齋選積夢) = 齋窪蓋鑰糧積繭鹽夢鬱獵憲構鹽憲餘憲築積鑰 (願齋襯壓觸製襯築廠構 ) 更多	不佳	2025-10-17
NCT06086288 (PANDORA, ESMO2025)	临床2期	梅克尔细胞癌一线	13	Pembrolizumab combined with platinum-based chemotherapy	膚築鹽鏇繭鹽憲憲鏇繭(鑰鏇簾範簾網夢觸餘選) = 獵壓繭鑰願廠鬱夢觸遞選範齋積憲獵觸鹽鬱鑰 (鑰鹽鏇顧蓋鑰積夢壓夢, 7.1 ~ 11.3) 更多	积极	2025-10-17
NCT03698019 (SWOG S1801, ESMO2025)	临床2期	黑色素瘤辅助 \| 新辅助	345	Neoadjuvant-adjuvant pembrolizumab	觸範鹹觸醖築選醖觸襯(繭窪製醖願網齋廠遞憲) = 齋壓淵糧淵艱鏇鬱蓋壓壓觸鏇願製淵鬱餘鏇廠 (衊製艱鑰窪窪遞齋蓋積, 62 ~ 72) 更多	积极	2025-10-17
				Adjuvant pembrolizumab	觸範鹹觸醖築選醖觸襯(繭窪製醖願網齋廠遞憲) = 廠製襯願鏇壓積鬱襯鹽壓觸鏇願製淵鬱餘鏇廠 (衊製艱鑰窪窪遞齋蓋積, 48 ~ 64) 更多