A Phase 2b, Randomized, Blinded Trial Investigating the Efficacy and Safety of Visugromab in Combination With Nivolumab and a Tyrosine Kinase Inhibitor Compared to Double Placebo and a Tyrosine Kinase Inhibitor in Participants With Unresectable or Metastatic Hepatocellular Carcinoma and Compensated Liver Function (Child-Pugh A) After Failure of First-Line Treatment That Included an Anti PD-(L)1 Compound (GDFATHER HCC-01)

This is a Phase 2b, randomized, blinded clinical trial investigating the efficacy and safety of visugromab in combination with nivolumab and a TKI compared to double placebo and a TKI in participants with unresectable or metastatic HCC and compensated liver function (Child-Pugh A) after failure of 1L treatment that included an anti-PD-(L)1 compound. The trial consists of 2 Parts: a non-randomized Safety-run-in part (Part 1) and the subsequent randomized part (Part 2) with 2 treatment arms (A and B). Randomization of participants into Treatment Arm A and B will continue until 40 efficacy-evaluable participants are enrolled into each Treatment Arm.

开始日期2026-02-01

申办/合作机构

CatalYm GmbH

NCT07112196

/ Recruiting临床2/3期

Adaptive, Phase 2/3, Randomized, Double-Blind Trial Investigating the Efficacy and Safety of Visugromab Versus Placebo in Patients With Cancer-associated Cachexia

A study of how well and safely a new drug called visugromab works in people with certain kinds of cancer (including lung and bowel cancer) and unintended weight loss known as cachexia. The main questions it aims to answer are:
* Does visugromab help participants put weight back on and have a better appetite?
* Does visugromab help participants move more and better?
* What medical problems do participants have when taking visugromab? Researchers will compare visugromab to a placebo (a look-alike substance that contains no drug).
Participants will visit the hospital or clinic once every 4 weeks to receive visugromab or placebo via a drip into a vein and to undergo checkups and tests.

开始日期2026-01-01

申办/合作机构

CatalYm GmbH

NCT07246863

/ Recruiting临床2期

Ph 2, Randomized, Blinded, Placebo-Controlled Trial Investigating the Efficacy and Safety of Visugromab and Nivolumab With or Without Docetaxel Versus Docetaxel in 2L Treatment of Participants With Metastatic NSCLC (GDFATHER-NSCLC-02)

This is an exploratory, signal-finding, randomized, placebo-controlled, blinded, multi-center phase 2b trial of the anti-GDF-15 antibody Visugromab (CTL-002) at two different dose levels plus Nivolumab with Docetaxel versus Visugromab at the higher dose plus Nivolumab with placebo versus double-placebo with Docetaxel, in participants that receive second-line treatment for non-squamous NSCLC after failure of prior first-line treatment including a CPI (checkpoint inhibitor).
The trial consists of 3 Parts: an open-label Safety Run-in part (Part A) followed by a subsequent randomized phase 2b part with 4 treatment arms. After the treatment of 15 participants with visugromab at the expansion dose, an interim safety and preliminary efficacy analysis will be conducted (Part B), followed by the treatment of the remaining participants (Part C).

开始日期2025-10-07

申办/合作机构

CatalYm GmbH

100 项与维苏格罗单抗相关的临床结果

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100 项与维苏格罗单抗相关的转化医学

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100 项与维苏格罗单抗相关的专利（医药）

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项与维苏格罗单抗相关的文献（医药）

2025-01-30·Nature

Neutralizing GDF-15 can overcome anti-PD-1 and anti-PD-L1 resistance in solid tumours

Article

作者: Trojan, Jörg ; Vilalta-Lacarra, Anna ; Fettes, Petra ; Richly, Heike ; Akdemir, Julia ; Chun, Felix Kyoung Hwan ; Hackl, Hubert ; Gajewski, Thomas F ; Racca, Fabricio ; Esteban-Villarrubia, Jorge ; Reis, Henning ; Rössler, Bernhard ; Torres-Jiménez, Javier ; Bargou, Ralf ; Lloyd, Peter ; Wild, Peter ; Trajanoski, Zlatko ; Alonso, Guzman ; Landa-Magdalena, Ana ; Auckenthaler, Alexandra ; Hermann, Frank ; Schuler, Martin ; Schuberth-Wagner, Christine ; Gjorgjioska, Ana ; Rodriguez Ruiz, Maria-Esperanza ; König, David ; Koster, Kira-Lee ; Foerster, Friedrich ; Melero, Ignacio ; Goebeler, Maria-Elisabeth ; Auer, Marlene ; Saavedra, Omar ; Koll, Florestan J ; Machacek, Matthias ; Dutta, Aradhana ; Gromke, Tanja ; Fridman, Wolf H ; Galle, Peter R ; de Miguel Luken, Maria ; Soto-Castillo, Juan José ; Eggenschwiler, Corinne ; Liebig, Mara ; Sanduzzi-Zamparelli, Marco ; Dummer, Reinhard ; Garralda, Elena ; Läubli, Heinz ; Hess, Dagmar ; Rüschoff, Josef ; da Silva, Antonio ; Tereshchenko, Anastasiia ; Rüdiger, Manfred ; Eggermont, Alexander M M ; Calvo, Emiliano ; L'Huillier, Phil ; Haake, Markus ; Fortuny, Marta ; Koch, Christine ; Klar, Kathrin ; Gogolla, Falk ; Moreno, Irene ; Sayehli, Cyrus ; Joerger, Markus ; Sabat, Paula ; Oberoi, Arjun ; Hernando-Calvo, Alberto ; Schmitt, Andreas M ; Reichhardt, Daniela ; Schöniger, Sandra ; Lichtenegger, Felix S ; Ramelyte, Egle ; Zink, Carina ; de Velasco, Guillermo ; Martín-Liberal, Juan ; Wischhusen, Jörg ; Reig, Maria ; Leo, Eugen

Cancer immunotherapies with antibodies blocking immune checkpoint molecules are clinically active across multiple cancer entities and have markedly improved cancer treatment¹. Yet, response rates are still limited, and tumour progression commonly occurs². Soluble and cell-bound factors in the tumour microenvironment negatively affect cancer immunity. Recently, growth differentiation factor 15 (GDF-15), a cytokine that is abundantly produced by many cancer types, was shown to interfere with antitumour immune response. In preclinical cancer models, GDF-15 blockade synergistically enhanced the efficacy of anti-PD-1-mediated checkpoint inhibition³. In a first-in-human phase 1-2a study (GDFATHER-1/2a trial, NCT04725474 ), patients with advanced cancers refractory to anti-PD-1 or anti-PD-L1 therapy (termed generally as anti-PD-1/PD-L1 refractoriness) were treated with the neutralizing anti-GDF-15 antibody visugromab (CTL-002) in combination with the anti-PD-1 antibody nivolumab. Here we show that durable and deep responses were achieved in some patients with non-squamous non-small cell lung cancer and urothelial cancer, two cancer entities identified as frequently immunosuppressed by GDF-15 in an in silico screening of approximately 10,000 tumour samples in The Cancer Genome Atlas database. Increased levels of tumour infiltration, proliferation, interferon-γ-related signalling and granzyme B expression by cytotoxic T cells were observed in response to treatment. Neutralizing GDF-15 holds promise in overcoming resistance to immune checkpoint inhibition in cancer.

2015-07-01·Arteriosclerosis, thrombosis, and vascular biology1区 · 医学

Choline Transporter-Like Protein-2

1区 · 医学

Article

作者: Santoso, Sentot ; Werth, Silke ; De Meyer, Simon F. ; Tjahjono, Yudy ; Bayat, Behnaz ; Berghöfer, Heike ; Deckmyn, Hans ; Sachs, Ulrich J.

Objective—:

In contrast to other antibodies involved in transfusion-related acute lung injury, anti–HNA-3a antibodies are incapable of inducing direct neutrophil activation and seem to interact with endothelial cells (ECs) primarily. In animal studies, anti–HNA-3a-mediated transfusion-related acute lung injury could be precipitated in the absence of neutrophils, but was stronger when neutrophils were present. In a different context the target protein of these antibodies, choline transporter-like protein-2 (CTL-2), was reported to interact with a protein of the inner ear carrying 2 von Willebrand factor (VWF) A-domains. These observations prompted us to investigate whether VWF might be involved in anti–HNA-3a-mediated neutrophil activation, and whether signaling via CD11b/CD18 is involved, as in various other experimental settings.

Approach and Results—:

Cell adhesion demonstrated specific binding of CTL-2 to VWF. Immunoprecipitation analysis of CTL-2/CD11b/CD18 coexpressing cells indicated that anti–HNA-3a colocalizes CTL-2 and CD11b/CD18 when VWF is present. Functional studies revealed that anti–HNA-3a-mediated neutrophil agglutination is an active, protein kinase C-dependent and partially Fc-dependent process. Agglutination and the production of reactive oxygen species seem to require the formation of a trimolecular complex between the target antigen (CTL-2), CD11b/CD18 and VWF. In line with these observations, anti–HNA-3a induced less severe transfusion-related acute lung injury and less neutrophil recruitment to the alveolar space in VWF knockout mice.

Conclusions—:

We introduce CTL-2 as a new binding partner for VWF. Interaction of neutrophils with VWF via CTL-2 allows anti–HNA-3a to induce signal transduction via CD11b/CD18, which leads to neutrophil activation and agglutination. In transfusion-related acute lung injury, this mechanism may further aggravate endothelial leakage.

CHINESE MEDICAL JOURNAL

Decoding GDF15: Impact on prostate cancer metabolism, chemoresistance, and clinical applications

Article

作者: Huang, Weichao ; Yang, Lu ; Li, Yifan ; Zhu, Weizhen ; Wei, Qiang ; Xiong, Xingyu ; Feng, Dechao ; Xu, Hang

Abstract:

Prostate cancer (PCa) presents a significant global health challenge, and cachexia in end-stage PCa further reduces survival time and deteriorates patient quality of life. This necessitates nuanced approaches to prevention, diagnosis, and treatment. This review analyzes the complex role of growth differentiation factor 15 (GDF15) in various aspects of PCa, including metabolism, chemoresistance, metastasis, and clinical implications. Mechanically, the interactions of GDF15 with PCa lipid metabolism and stromal activation are hypothesized to drive PCa progression and promote cachexia. GDF15’s role in PCa bone metastasis is mediated through interactions with osteoblasts and osteoclasts. Furthermore, GDF15’s role in chemoresistance emphasizes its impact on drug responses and suggests a potential therapeutic target. Clinically, GDF15 has shown potential as a biomarker, offering diagnostic precision and prognostic value, particularly when combined with established markers such as prostate-specific antigen. The review concludes with a discussion on several monoclonal antibodies targeting GDF15 in clinical trials, such as AV-380, NGM120, Visugromab, and AZD8853, highlighting promising strategies for novel therapies and precision medicine.

项与维苏格罗单抗相关的新闻（医药）

2025-12-18

·药研网

GDF15从“潜力靶点”向“验证靶点”过渡，商业价值有望比肩PD-1?

前言在实体瘤研究中，肿瘤周围的“正常”癌旁组织，长期被视为相对被动的背景结构。然而，越来越多证据表明，癌旁微环境并非沉默旁观者，而是深度参与肿瘤进展的重要调控者。 2025年12月3日，复旦大学附属肿瘤医院与上海交通大学医学院附属第一人民医院团队在 Nature Aging（IF = 19.4）发表研究，首次揭示衰老的癌旁结肠上皮细胞（CEC）分泌的GDF15，通过激活糖酵解–组蛋白乳酰化反馈环路，调控结直肠癌的进展机制。[1] 该研究揭示了一种结直肠癌细胞与癌旁上皮细胞之间的全新代谢–表观遗传通讯模式，将GDF15的作用边界从肿瘤细胞本身拓展至癌旁衰老上皮细胞与微环境调控层面，显著拓宽了该靶点在肿瘤领域的干预想象空间。 GDF15靶点简介生长分化因子15（GDF15），又称巨噬细胞抑制细胞因子（MIC-1），是一种应激诱导型分泌蛋白，以25 kDa二聚体形式循环，由两个含112个氨基酸的多肽链经二硫键连接组成。GDF15在正常生理条件下表达水平较低，主要在肝、肾、心、肺等器官受到损伤或细胞应激时上调表达。近年来研究发现，GDF15在炎症调节、组织修复、代谢紊乱和细胞应激等生理及病理过程中均发挥关键作用，且其表达可由多种应激因子（如细胞损伤、氧化应激、抗糖尿病药物二甲双胍等）诱导上升。[2] Figure.Structure of GDF-15 GDF15介导的信号通路 GDF15通过与其唯一已知受体GFRAL（胶质细胞源性神经营养因子家族α样受体）结合，形成配体-受体复合物，并招募辅助受体RET，从而激活一系列下游信号通路，包括RET、AKT、ERK和PLC-γ1等通路。该受体主要表达于延髓的孤束核区，’因此 GDF15–GFRAL 轴在调控食欲、能量代谢和体重稳态中发挥核心作用，并在代谢性疾病和肿瘤相关综合征中展现出重要干预潜力。 Figure. Intracellular signaling pathways.[3] 吉满生物基于前沿研究与市场需求，创新推出GDF15药物研发全流程解决方案，完整覆盖稳定表达细胞系、高灵敏度报告基因细胞系及高纯度抗体蛋白产品系列，为抗体药物体外药效评估提供精准工具，高效支持临床前研究及IND申报。我们拥有HEK293、Jurkat E6.1、CHO-K1细胞商业化使用授权，同时拥有HEK293细胞中国内地定向用途分授权独家代理，可提供合规性授权解决方案。为客户从早期研发到产品上市保驾护航。咨询吉满客服联系同微信：18916119826。 “一靶多病”的治疗潜力肿瘤免疫逃逸：破解“冷肿瘤”的新钥匙 GDF15在肿瘤微环境中高表达，抑制树突状细胞成熟、T细胞活化及浸润，帮助肿瘤逃避免疫监视。其“胎盘式免疫屏障”机制也被肿瘤细胞利用，导致免疫治疗耐药。靶向GDF15有望打破免疫抑制，增强PD-1/PD-L1疗法效果，为冷肿瘤患者提供新解法。恶病质治疗的新希望癌症恶病质（Cancer Cachexia）是一种常见且高度致残的癌症并发症，这类代谢综合征在50%~80%的癌症患者中出现，表现为厌食、体重骤降、肌肉和脂肪萎缩，严重影响生存质量和治疗耐受性。大量研究表明，GDF15是癌症恶病质的驱动因子之一。通过作用于中枢神经系统的 GDF15–GFRAL 通路，GDF15 可显著抑制食欲、扰乱能量代谢稳态，从而加速体重和肌肉丢失。当前，靶向 GDF15 的治疗策略正快速推进，以辉瑞开发的 Ponsegromab（珀塞古单抗）为代表的抗 GDF15 单克隆抗体，已在 II 期临床研究中显示出改善患者体重、食欲、身体功能及恶病质症状的积极疗效，为这一长期缺乏有效治疗手段的领域提供了全新的解决方案。肥胖与糖尿病：继GLP-1后的中枢减重新靶点 2017年前后，医学界发现了GDF15在肥胖治疗领域的潜力，礼来、诺和诺德和强生三家制药巨头同时在Nature Medicine明确指出GFRAL是GDF15的高亲和力受体，在减少摄食和降低体重机制中发挥着核心作用。这是科学家们首次确定GDF15调节体重的核心机制和关键受体，为肥胖和Ⅱ型糖尿病的治疗提供了绝佳的靶点。 2023年6月28日，加拿大McMaster大学Dr. Gregory Steinberg课题组的王冬冬博士领导的GDF15研究项目在Nature上发表成果，系统阐释了GDF15通过提高肌肉能量消耗发挥减重作用的机制。 Figure.连接GDF15与GFRAL和肾上腺素能受体的生物回路的机制图，以在热量限制期间维持肌肉的能量消耗[4] NAFLD与心血管疾病：炎症与代谢调控新窗口 GDF15在非酒精性脂肪肝中可改善肝脏代谢、减轻炎症；同时作为心血管事件的应激标志物，GDF15 也具备潜在的早期诊断和干预价值，正在成为慢病管理领域的新兴关注点。 GDF15靶点在研格局目前，全球 GDF15 靶向药物仍处于相对早期阶段，药物类型以单抗为主，最高临床阶段为临床II期，包括CatalYm的Visugromab、辉瑞的ponsegromab，NGM Bio的NGM120。数据来源：药研网辉瑞抗GDF15单抗Ponsegromab 去年9月，辉瑞在欧洲肿瘤内科学会（ESMO）年会上公布Ponsegromab在临床II期研究中的积极结果：在所有测试的剂量中，ponsegromab组均达到了体重相对于基线的变化，与安慰剂相比，在12周时评估的最高剂量下体重平均增加5.6%；ponsegromab在所有剂量水平下均被认为安全且耐受性良好的，而且在测试的最高剂量下，患者食欲和恶病质症状、身体活动和肌肉质量较基线有所改善。按照辉瑞此前披露的计划，Ponsegromab预计在2025年推进III期临床试验；2022年底，Ponsegromab在国内也获批临床，成为国内首款获批临床的GDF15单抗。[5] CatalYm—Visugromab Visugromab可中和肿瘤衍生的GDF-15，是一种局部作用的免疫抑制剂，可促进免疫疗法耐药性。此前在2024年ASCO年会上公布了1期临床研究结果，使用 Visugromab 中和 GDF-15 可逆转关键的癌症耐药机制，通过重新激活免疫细胞和肿瘤浸润来恢复有效的抗肿瘤反应。Visugromab 在临床1期试验中已展现出良好的安全性，目前正在针对多种实体瘤适应症开展临床2期研究。劲方医药GDF15/IL-6双抗GFS202A GFS202A为拮抗性双特异性抗体，是全球首个恶病质双抗疗法及GDF15/IL-6双抗产品，也是国内首个进入临床的恶病质靶向疗法及GDF-15抗体类药物。今年3月，劲方医药宣布，GFS202A针对肿瘤恶病质前期及恶病质期患者开展一项开放标签、多中心的I期临床研究试验申请获得国家药品监督管理局批准。此外，针对GDF-15靶点的其他药物类型有纳米抗体、融合蛋白、重组蛋白和小分子化药，适应症多为肥胖。其中由美国强生开发小分子药物JNJ-9090处于临床1期阶段，这是一款GDF-15调节剂，其作用机制主要是通过激活GFRAL受体来促进产热和脂解。这些靶向GDF-15的临床前阶段药物种类丰富，也为未来的药物研发提供了积极的信号。总结 Nature Aging 的最新研究显著拓展了该靶点在实体瘤中的作用边界。综合来看，GDF15 正逐步从应激与代谢相关因子，升级为连接肿瘤微环境、免疫调控与系统性能量代谢的关键枢纽分子。结合其在癌症恶病质、免疫耐药及代谢性疾病中的临床推进，GDF15 已展现出清晰的“一靶多病”开发潜力，有望成为免疫、代谢与肿瘤微环境协同干预的重要切入点。吉满生物吉满生物基于前沿研究与市场需求，创新推出GDF15药物研发全流程解决方案，完整覆盖稳定表达细胞系、高灵敏度报告基因细胞系及高纯度抗体蛋白产品系列。 1 靶点相关细胞系：适用于药物功能筛选、活性评价、药效学研究及信号通路验证 2 高活性重组蛋白：满足结合分析、筛选及免疫研究需求 3 高特异性抗体：提供经严格验证的抗体产品，支持流式细胞术、免疫组化、Western Blot、ELISA 等多种检测应用，确保实验结果准确可靠 GDF15相关产品及数据 01 细胞系数据展示（部分） GM-C06718 H_GDF15 Reporter 293 Cell Line，传代稳定，30代信号响应表现仍然优秀。功能验证，结果表现可靠，可以有效帮助用户进行药物筛选和活性评价。使用Human GDF15 Protein; His Tag稳定性验证结果使用Anti-GDF15 hIgG1 Reference Antibody(Ponsbio)抗体block验证结果 02 蛋白数据展示（部分） GM-87627RP 经ELISA验证蛋白表现出优异的活性，信号强、背景低，可应用于抗体筛选及结合分析等实验 Human GDF15 Protein; His Tag ELISA验证 Human GDF15 Protein; His Tag ELISA验证 Human GDF15 Protein; His Tag ELISA验证经Cell-based验证，该蛋白在体外细胞体系中表现出优异的生物学活性，可有效激活目标信号通路，适用于功能分析、受体激动实验及药理机制研究等应用。 Human GDF15 Protein; His Tag cell base 联系我们吉满生物(Genomeditech)成立于2011年，是专业从事生物科技服务和前沿技术研发的高新技术企业。吉满生物专注为生物药开发赋能，自主创立了国内知名的细胞系品牌-DDXCELL，目前已布局近400个热门靶向药靶点，超1000株现货单克隆细胞系，涵盖GPCR、细胞因子、免疫检查点、TAA等多领域，做到进口细胞的国产替代。此外，吉满生物还可在药物研发进程中提供一系列抗体、蛋白产品，旨在为客户提供高效的研发工具和解决方案! 扫码咨询扫码找现货参考资料 1.https://www.nature.com/articles/s43587-025-01023-9 2. Delrue, C., et al., Growth differentiation factor 15 (GDF-15) in kidney diseases. Adv Clin Chem, 2023. 114: p. 1-46. 3. Adela, R. and S.K. Banerjee, GDF-15 as a Target and Biomarker for Diabetes and Cardiovascular Diseases: A Translational Prospective. J Diabetes Res, 2015. 2015: p. 490842 4. Wang, D., Townsend, L.K., DesOrmeaux, G.J. et al. GDF15 promotes weight loss by enhancing energy expenditure in muscle. Nature 619, 143–150 (2023). https://doi.org/10.1038/s41586-023-06249-4 5.https://www.esmo.org/oncology-news/inhibition-of-gdf-15-with-ponsegromab-results-in-increased-weight-gain-and-overall-activity-level-and-reduced-cancer-cachexia-symptoms.

2025-12-02

·Business Wire

CatalYm Announces First Patient Dosed in Phase 2b Trial Evaluating Visugromab in Combination with Chemoimmunotherapy as Second-Line Treatment in Metastatic Non-squamous NSCLC

MUNICH & SAN FRANCISCO--(BUSINESS WIRE)--CatalYm today announced that the first patient has been dosed in the randomized Phase 2b GDFATHER‑NSCLC‑02 (GDF‑15 Antibody‑MediaTed‑Human‑Effector‑T‑Cell Relocation) trial (NCT07246863). The trial evaluates the company’s lead anti-GDF-15 antibody visugromab as a second-line treatment in patients with metastatic non-squamous non-small cell lung cancer (nsq NSCLC) who have progressed following initial systemic treatment including an approved immune checkpoint inhibitor. The trial will assess multiple treatment strategies combining visugromab with an anti-PD-1 antibody and the chemotherapy docetaxel, including a chemo-free regimen. Standard-of-care chemotherapy alone will serve as the control arm. The trial consists of a safety run-in followed by a randomized phase evaluating visugromab in the different combination regimen settings. Visugromab is a humanized, monoclonal antibody that targets Growth Differentiation Factor-15 (GDF-15), a tumor-derived cytokine known to drive immune suppression and resistance to anti-PD-(L)1 therapies. In the exploratory Phase 1/2a GDFATHER trial (NCT04725474), visugromab demonstrated encouraging anti-tumor activity when combined with an anti-PD-1 antibody in advanced-stage, anti-PD-(L)1 relapsed/refractory NSCLC patients, demonstrating deep and durable responses, with a median duration of response of 32.2 months and a favorable safety profile. In addition to its ability to restore immune activation, visugromab also showed potential to alleviate cancer cachexia, a severe condition limiting treatment tolerability and responsible for 20-40% of cancer deaths.1 “The decision to evaluate visugromab in second-line nsq NSCLC, in addition to the first-line setting, was driven by the strength of our Phase 1/2a data in heavily pretreated patients, where we observed deep and durable responses well beyond those typically seen with other therapies in this setting,” said Sujata Rao, MD, Chief Medical Officer at CatalYm. “By neutralizing GDF-15, a key driver of immune suppression, visugromab may overcome resistance, restore responsiveness to immunotherapy and extend the benefit of anti-PD-1 agents. Its additional potential to mitigate cancer cachexia and support tolerance to chemotherapies and other anti-cancer regimens offers a distinct advantage in this difficult-to-treat population.” “We are expanding visugromab’s development into key settings where immune resistance severely limits treatment options,” said Scott Clarke, Chief Executive Officer at CatalYm. “Second-line nsq NSCLC is a particularly challenging indication with limited benefit from current standard-of-care. This trial builds on the compelling rationale for GDF-15 neutralization and is part of our late-stage development program to deliver visugromab’s potential to patients in urgent need of better solutions.” The randomized, multi-arm Phase 2b GDFATHER-NSCLC-02 trial will enroll approximately 131 patients across multiple sites in the US, EU and Switzerland. Following the safety run-in, patients will be randomized into one of four treatment arms: Visugromab + anti-PD-1 inhibitor + chemotherapy Visugromab + anti-PD-1 inhibitor (chemo-free) Visugromab (at lower dose) + anti-PD-1 inhibitor + chemotherapy Chemotherapy alone (control) The primary endpoint of the study is objective response rate (ORR) defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary endpoints include duration of response (DOR), progression-free survival (PFS), overall survival (OS), participant weight course over time and safety-related measures. About NSCLC Lung cancers remain the leading cause of cancer-related mortality globally and non-small cell lung cancers (NSCLCs) account for approximately 87% of the 210,000 annual lung cancer diagnoses in the US2. Five-year survival rates in the US for non-squamous NSCLC are low: 12.8% for adenocarcinoma and 5.1% for large-cell carcinoma3. 70-85% of NSCLC patients either exhibit primary resistance to PD-1 blockade or develop acquired resistance to immunotherapy4, emphasizing the need for innovative approaches to overcome immunotherapy resistance. About Visugromab Visugromab is a monoclonal antibody that neutralizes Growth Differentiation Factor-15 (GDF-15), a locally acting immunosuppressant produced by tumors which fosters resistance and drives cachexia in people with cancer. Neutralizing GDF-15 with visugromab reverses key cancer resistance mechanisms to reinstate an efficient anti-tumor response by re-enabling immune cell activation, proliferation and induction of interferon-γ. In addition, visugromab also mitigates cancer cachexia, a severe condition affecting a significant number of advanced cancer patients by inhibiting the activation of the GFRAL pathway in the brainstem, a key driver of weight loss and appetite suppression in cancer patients. About CatalYm CatalYm is developing visugromab, a first-in-class anti-GDF-15 antibody, in solid tumors and cachexia. In its first-in-human Phase 1/2a study, visugromab demonstrated durable anti-tumor efficacy with long-lasting objective responses in relapsed and refractory metastatic solid tumor patients in combination with anti-PD-1 treatment. In addition, data from the same study demonstrated that visugromab can significantly counteract the effects of cachexia in these patients. This data was published in Nature and presented at the International Conference on Sarcopenia, Cachexia & Wasting Disorders. CatalYm is now advancing visugromab into multiple Phase 2b studies including first-line metastatic non-squamous NSCLC (NCT07098988), second-line metastatic non-squamous NSCLC (NCT07246863) and cachexia (NCT07112196). Founded in 2016 and based in Munich, Germany and San Francisco, USA, CatalYm is backed by leading international investors including Canaan Partners, Omega Funds, Bioqube Ventures, Forbion, Jeito Capital, Brandon Capital, Gilde Healthcare, Novartis Venture Fund, Vesalius, Bayern Kapital, BioGeneration Ventures, and Coparion. 1 Fearon K. et al. Lancet Oncol. 2011;12(8):489–495. 2 American Cancer Society, Key Statistics for Lung Cancer, 2025: https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html, retrieved on Aug. 06, 2025 3 https://seer.cancer.gov/ 4 Mariniello A, Borgeaud M, Weiner M, Frisone D, Kim F, Addeo A. Primary and Acquired Resistance to Immunotherapy with Checkpoint Inhibitors in NSCLC: From Bedside to Bench and Back. BioDrugs. 2025 Mar;39(2):215-235. doi: 10.1007/s40259-024-00700-2. Epub 2025 Feb 15. PMID: 39954220; PMCID: PMC11906525.

免疫疗法临床2期临床结果

2025-10-26

·科学网

GDF15阻断剂：癌症恶病质候选药物进入首个关键临床试验

GDF15阻断剂：癌症恶病质候选药物进入首个关键临床试验Pfizer与GDF15阻断剂：癌症恶病质市场迎来关键突破近年来，癌症药物研发持续集中在肿瘤本身，而癌症恶病质长期被忽视。该综合征不仅导致患者体重下降、肌肉和脂肪流失，还降低治疗耐受性和生存率，约占癌症死亡的20�30%。在长期缺乏有效药物干预的背景下，GDF15阻断剂正在成为产业关注的新焦点。研发进展与机制解析GDF15（Growth Differentiation Factor-15）隶属于TGF-β超家族，自20世纪90年代被发现以来，因其多效性与广泛表达而受到关注。2006�2007年的研究首次揭示GDF15过表达与体重下降密切相关，动物实验显示，抗体干预可逆转这一消瘦过程。进一步机制研究明确，GDF15通过与脑干GFRAL受体结合，抑制食欲中枢活动，从而导致体重持续下降。这一发现为恶病质药物研发提供了明确的靶点。基于该通路，辉瑞（Pfizer）的 ponsegromab 与CatalYm的 visugromab 应运而生，均为GDF15通路阻断型抗体。不同于以往通过激活GDF15-GFRAL信号治疗肥胖的策略，辉瑞选择“逆向干预”路径，通过阻断该信号恢复食欲、减缓恶病质进展。目前，这两款抗体药物均进入关键临床阶段：ponsegromab 即将启动II/III期临床试验，visugromab 预计在2026年初开启类似试验。专家普遍认为，这一阶段性进展代表了恶病质治疗领域的关键拐点――若III期结果积极，将标志着该领域从长期空白迈向产业化突破。临床数据与关键指标辉瑞II期试验共招募187例高GDF15水平的癌症恶病质患者，采用安慰剂对照及三档剂量设计。数据显示：高剂量组12周体重增加2.81公斤（相较安慰剂）；食欲及恶病质症状改善明显；活动水平增加；安全性良好，不良事件与安慰剂相当，主要包括腹泻、癌症进展、贫血、低钾血症、恶心、呕吐及发热。即将启动的II/III期关键试验计划招募980余例转移性胰腺癌患者，评估联合全身化疗的ponsegromab疗效。主要终点为：12周体重变化百分比（评估药物减缓消瘦效果）；FAACT 5项食欲量表评分（患者自评食欲及生活质量）。此外，总生存期（OS）作为次要终点，用于探索药物是否可改善患者整体生存。辉瑞认为，成功改善食欲和体重的药物，有望增强患者免疫力和对化疗毒性的耐受性。市场潜力与商业前景癌症恶病质长期以来缺乏行业重视，导致该领域药物开发几乎处于空白状态。尽管临床上存在如低剂量奥氮平等成本较低的对症替代方案，但若GDF15阻断剂能在改善体重和生活质量之外进一步延长患者生存期，其市场价值仍将十分可观。据分析机构预测，仅癌症消瘦症一项的潜在市场规模就可达1000亿美元，尚未包括心衰、慢阻肺等相关适应症的扩展空间。辉瑞（Pfizer）的竞争优势体现在三方面：• 前瞻布局――率先进入该领域并掌握核心临床数据；• 临床信号明确――II期试验显示显著疗效及良好耐受性；• 拓展潜力广泛――未来有望扩展至多种实体瘤及与免疫治疗的联合方案。CatalYm紧随其后，计划于2026年启动涵盖约500例患者的II/III期临床试验，以进一步验证visugromab在癌症恶病质及免疫联合治疗中的应用前景。从产业视角来看，GDF15阻断剂有望成为癌症支持治疗领域首个具有突破性意义的创新药物类别。研发趋势与未来布局当前，产业链关注点集中在三方面：早期干预：阻断GDF15以预防体重下降，提升化疗耐受性；组合策略：与PD1/PDL1抑制剂联合，利用GDF15阻断的免疫调控效应增强抗肿瘤活性；新靶点拓展：MC3/4R、NPY、CCL2等新兴靶点推动行业技术迭代，为未来药物组合和差异化竞争提供空间。业内专家普遍认为，癌症恶病质正进入快速发展期：从基础研究、药物验证到产业化布局，正形成完整的研发闭环。GDF15阻断剂的临床数据和商业前景，将对资本关注度、投资热度和市场格局产生深远影响。总结Pfizer ponsegromab及CatalYm visugromab代表了癌症恶病质领域首次系统的产业化尝试。凭借明确的靶点、高信号的中期临床数据以及潜在适应症拓展空间，GDF15阻断剂有望开辟癌症恶病质治疗的新赛道。如果未来证明能够改善患者生存期，其产业价值和市场潜力将进一步放大，为制药企业提供新的增长引擎。英文原文于2025年10月10日发表于 Nature Reviews Drug Discoveryhttps://www.nature.com/articles/d41573-025-00168-x转载本文请联系原作者获取授权，同时请注明本文来自刘玉娥科学网博客。链接地址：https://wap.sciencenet.cn/blog-3592244-1507565.html?mobile=1

临床结果临床2期

100 项与维苏格罗单抗相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
恶病质	临床3期	美国	CatalYm GmbH	2026-01-01
肝细胞癌	临床2期	美国	CatalYm GmbH	2026-02-01
转移性非小细胞肺癌	临床2期	美国	CatalYm GmbH	2025-08-01
转移性非小细胞肺癌	临床2期	德国	CatalYm GmbH	2025-08-01
转移性非小细胞肺癌	临床2期	西班牙	CatalYm GmbH	2025-08-01
转移性非小细胞肺癌	临床2期	瑞士	CatalYm GmbH	2025-08-01
转移性非鳞状非小细胞肺癌	临床2期	美国	CatalYm GmbH	2025-08-01
转移性非鳞状非小细胞肺癌	临床2期	德国	CatalYm GmbH	2025-08-01
转移性非鳞状非小细胞肺癌	临床2期	西班牙	CatalYm GmbH	2025-08-01
转移性非鳞状非小细胞肺癌	临床2期	瑞士	CatalYm GmbH	2025-08-01

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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


NCT04725474 (GDFATHER-01, ESMO2025)	临床1/2期	肝细胞癌 \| 非小细胞肺癌 \| 尿路上皮癌	77	Visugromab (V) + Nivolumab (N) (non-squamous NSCLC + urothelial cancer + hepatocellular cancer + anti-PD1/-L1 relapsed/refractory)	糧顧淵構顧鹽觸鏇蓋壓(鹽餘齋繭築齋範鏇積淵) = 鹽鹽願鏇糧鹽網顧獵簾鏇鏇鹽鹹淵蓋範鏇製網 (顧積廠醖鹹齋築餘鬱夢 ) 更多	积极	2025-10-17
NCT06059547 (GDFather-NEO, ESMO2025)	临床2期	肌层浸润性膀胱癌新辅助	31	Nivolumab+Visugromab	鹽壓壓遞廠襯襯鏇憲窪(顧醖壓範簾壓憲夢觸艱) = 範顧遞鏇鑰製糧醖顧鹽觸夢窪繭顧鏇鏇築壓艱 (衊夢夢壓鹹壓簾壓遞選 ) 更多	积极	2025-10-17
NCT06059547 (GDFather-NEO, ESMO2025)	临床2期	肌层浸润性膀胱癌新辅助	31	Nivolumab+Placebo	鹽壓壓遞廠襯襯鏇憲窪(顧醖壓範簾壓憲夢觸艱) = 壓簾鬱壓鬱網鹽鹹鑰蓋觸夢窪繭顧鏇鏇築壓艱 (衊夢夢壓鹹壓簾壓遞選 ) 更多	积极	2025-10-17
NCT04725474 (GDFATHER, BusinessWire) 人工标引	临床1/2期	肝细胞癌 \| 实体瘤 \| 非鳞状非小细胞肺癌 ... 更多	-	visugromab (non-squamous NSCLC)	壓淵積構廠鑰廠遞願淵(夢獵簾積夢範齋膚鹽鑰) = 觸鏇膚積憲淵獵齋鹹醖觸醖淵積鬱齋鑰簾襯蓋 (鏇構齋淵憲鹽餘築築醖 ) 更多	积极	2024-12-11
NCT04725474 (GDFATHER, BusinessWire) 人工标引	临床1/2期	肝细胞癌 \| 实体瘤 \| 非鳞状非小细胞肺癌 ... 更多	-	visugromab (UC)	壓淵積構廠鑰廠遞願淵(夢獵簾積夢範齋膚鹽鑰) = 鹹繭醖窪製廠築鏇壓顧觸醖淵積鬱齋鑰簾襯蓋 (鏇構齋淵憲鹽餘築築醖 ) 更多	积极	2024-12-11
NCT04725474 (GDFATHER, Biospace) 人工标引	临床1/2期	肝细胞癌 \| 非小细胞肺癌 \| 尿路上皮癌	-	Visugromab + Nivolumab	鬱鏇鹽憲積夢遞淵觸餘(積範製衊衊壓獵糧壓鏇) = 構顧選選餘襯齋襯餘襯範膚鬱網積壓簾繭蓋築 (鏇鏇窪鬱構糧鑰艱淵築 )	积极	2024-06-02
NCT04725474 (GDFATHER, Biospace) 人工标引	临床1/2期	肝细胞癌 \| 非小细胞肺癌 \| 尿路上皮癌	-	Visugromab + Nivolumab (NSCLC)	齋憲願艱鬱糧築襯築糧(壓選膚夢醖鹹衊鬱鬱淵) = 構糧顧簾廠構膚鹹簾鬱繭襯顧襯繭廠夢鑰遞鑰 (膚衊膚齋願範餘範憲醖 )	积极	2024-06-02
NCT04725474 (GDFather, ASCO2024) 人工标引	临床2期	肝细胞癌 \| 鳞状非小细胞肺癌 \| 尿路上皮癌	87	Visugromab 10 mg/kg + Nivolumab 240 mg Q2W	廠積齋憲壓蓋齋糧醖積(觸憲鹹簾夢鏇繭醖製齋) = 簾壓築鑰鏇網憲繭顧膚構範窪網鑰簾顧鹽廠製 (壓蓋衊獵壓鹽鬱願觸壓 ) 更多	积极	2024-05-24
NCT04725474 (GDFather, ASCO2024) 人工标引	临床2期	肝细胞癌 \| 鳞状非小细胞肺癌 \| 尿路上皮癌	87	Visugromab 10 mg/kg + Nivolumab 240 mg Q2W (NSCLC)	-	积极	2024-05-24
NCT04725474 (GDFATHER-2, Biospace) 人工标引	临床2期	晚期非小细胞肺癌 \| 尿路上皮癌 PD-L1 Positive	27	Visugromab+nivolumab (NSCLC)	襯製獵觸簾鹹鑰壓積構(廠蓋鬱選衊構獵願鑰夢) = 鹽鬱願鏇顧憲糧繭範願廠簾餘鬱餘遞夢顧鬱積 (簾窪蓋選遞糧築選簾築 )	积极	2023-12-06
NCT04725474 (ESMO_IO2023)	临床2期	实体瘤 \| 非小细胞肺癌 \| 膀胱癌 PD-L1+	114	Visugromab 10 mg/kg + Nivolumab 240 mg	願鹽願鬱範廠積鬱醖構(壓廠糧蓋齋獵繭膚繭衊) = 獵艱襯醖鹹艱襯鏇衊構繭鑰壓膚鹹築淵膚蓋窪 (齋觸鏇觸壓積鏇糧壓構 )	积极	2023-12-06
NCT04725474 (GDFATHER, ASCO 12023 \| ASCO 22023) 人工标引	临床2期	实体瘤	79	Nivolumab 240 mg+visugromab 10 mg/kg	餘築願築衊積製獵獵範(繭蓋鹹積齋膚淵窪淵鏇) = 衊築願願壓鹽鑰顧窪糧淵廠繭築簾簾壓衊築繭 (願壓蓋簾餘鬱艱齋壓鹽 ) 更多	积极	2023-05-31
NCT04725474 (GDFATHER-1, ESMO2022) 人工标引	临床1期	复发性实体肿瘤	25	CTL-002 0.3-20 mg/kg+Nivolumab	願鬱膚遞鏇窪齋觸襯衊(構選繭壓襯鹽遞顧觸廠) = 淵齋衊壓簾鬱艱顧糧遞鏇膚觸鹹範襯鏇選衊鹹 (夢廠獵鹹衊鹹淵觸簾膚 ) 更多	积极	2022-09-10