Phase II Trial of Siltuximab for Cytokine Release Syndrome Prophylaxis Prior to Treatment With Teclistamab in Relapsed or Refractory Multiple Myeloma (RRMM)

The purpose of this study is to examine the safety, efficacy and feasibility of the use of one standard dose of siltuximab prior to teclistamab infusion. Siltuximab is an investigational (experimental) drug that works by binding directly to human interleukin-6 (IL-6). IL-6 is a cytokine; these are products that are secreted by certain cells of the immune system and effect other cells in participant's body. IL-6 regulates immune, inflammatory and metabolic processes. Siltuximab has already been tested and approved for use by the FDA in participants with a condition called multicentric Castleman's disease, which is a lymphoproliferative disorder. This study is being conducted to investigate if administration of a single dose of siltuximab will reduce the rates of and severity of Cytokine Release Syndrome (CRS) and Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS) in participants prior to teclistamab administration. CRS and ICANS are adverse effects commonly experienced by participants being treated with teclistamab that are related to inflammation in the body. Siltuximab is experimental because it is not approved by the Food and Drug Administration (FDA) for prophylactic use prior to administration of teclistamab infusion.

开始日期2025-01-01

申办/合作机构

The Case Comprehensive Cancer Center

NCT06447376 / Not yet recruiting临床1期IIT

Pilot Safety-feasibility Study of Cytokine Release Syndrome Prophylaxis and Treatment with Siltuximab Prior to Epcoritamab

The goal of this clinical trial is to is to determine the safety, feasibility and efficacy of siltuximab prophylaxis of cytokine release syndrome and neurotoxicity occurring after epcoritamab subcutaneous administration for participants with large b-cell lymphoma (DLBCL) or follicular lymphoma (FL).
Participants will receive siltuximab, prior to the injection of epcoritamab. Epcoritamab is administered in 28 day cycles for one year. After this injection, the physician will continue to watch participants for side effects and follow the condition for a minimum of 60 days.

开始日期2024-12-01

申办/合作机构

The Case Comprehensive Cancer Center

[+3]

NCT06470971 / Recruiting临床2期IIT

Immune Checkpoint Inhibitor Rechallenge in Combination With Siltuximab Prophylaxis for Patients Who Had Prior Immune-Related Adverse Event (CIRES Trial)

This phase II trial studies how well giving siltuximab during the reintroduction (rechallenge) of immune checkpoint inhibitor (ICI) therapy works in preventing severe immune-related adverse events (irAEs) in patients with cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Immune checkpoint inhibitors, such as anti-PD1 and anti-PD-L1 monoclonal antibodies, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. The use of ICI therapy may lead to severe irAEs that can affect essentially any organ system in the body. Severe irAEs may lead to the early stopping of life saving treatment. Most patients that stop ICI therapy early will eventually progress and require additional treatment. Sometimes the decision is made to rechallenge with ICI therapy. Many patients who developed severe irAEs during initial ICI therapy are at risk for developing severe irAEs again during the rechallenge. Siltuximab is a monoclonal antibody that binds to receptors for a protein called interleukin-6 (IL-6). This may help lower the body's immune response and reduce inflammation. Giving siltuximab during ICI rechallenge may help prevent severe irAEs in patients with advanced cancer.

开始日期2024-07-31

申办/合作机构

Ohio State University Comprehensive Cancer Center

100 项与司妥昔单抗相关的临床结果

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100 项与司妥昔单抗相关的转化医学

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100 项与司妥昔单抗相关的专利（医药）

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373

项与司妥昔单抗相关的文献（医药）

2024-10-01·Cancer Reports

Cytokine Release Syndrome Associated With Immune‐Modulating Chemotherapy: Potential Mitigating Role of Intravenous Omega‐3 Fatty Acid Triglycerides

Review

作者: Bistrian, Bruce R. ; Driscoll, David F.

ABSTRACT:

Background:

Patient susceptibility to cytokine release syndrome (CRS) resulting from immune‐modulating chemotherapy has profound implications for clinical outcome. This is particularly true for patients receiving CAR T‐cell therapy. First‐line pharmacotherapy for CRS includes the administration of the IL‐6 receptor‐binding monoclonal antibody tocilizumab, or tocilizumab and corticosteroids. Other agents, such as siltuximab, anakinra, and dasatinab are also being explored for refractory cases of CRS. This review summarizes the potential role of omega‐3 fatty acids, that is, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at ameliorating CRS in cancer patients receiving immune‐modulating chemotherapy, and is compared with current treatment strategies to reduce the severity of the inflammatory response.

Recent Findings:

Selective blockade of specific proinflammatory mediators (e.g., IL‐6) is effective, but carries a significant risk of serious opportunistic infections. In contrast, omega‐3 fatty acids affect multiple triggers underlying the inflammatory response (i.e., prostaglandins, leukotrienes, transcription factors, and specialized proresolving molecules), and its major limitation is avoidance of hypertriglyceridemia, which can be managed by reducing the rate of intravenous administration. This discussion proposes a novel approach by continuous infusion of omega‐3 fatty acids to modulate the intensity of the severe systemic inflammatory response from CRS. The purpose of this review is to highlight the potential clinical benefits of a specialized omega‐3 fatty acids dosage form to mitigate the severity of CRS as a hypothetical alternative to current treatment.

Conclusion:

Optimizing the formulation, for example, enriched fish oil that meets drug concentration standards for EPA and DHA, a continuous infusion rate, reductions in long‐chain saturated fatty acids concentrations, and addition of medium‐chain triglycerides to improve EPA + DHA utilization and physical stability are key pharmaceutical factors. This may result in a safer and more effective option than targeted abrogation of cytokines and consequent risks of adverse drug reactions, but will require formal study in randomized control trials in humans.

2024-09-12·Nature Communications

A metabolic crosstalk between liposarcoma and muscle sustains tumor growth.

Article

作者: Prieto Romero, Jaime ; Carrere, Sebastien ; Quignot, Chloé ; Perot, Gaelle ; Riscal, Romain ; Riquier-Morcant, Blanche ; Chibon, Frédéric ; Gayte, Laurie ; Pomiès, Pascal ; Cisse, Madi Y ; Watson, Sarah ; Manteaux, Gabrielle ; Firmin, Nelly ; Heuillet, Maud ; Jacq, Solenn ; Sengenes, Coralie ; Fourneaux, Benjamin ; Larroque, Marion ; Bellvert, Floriant ; Linares, Laetitia K ; Amsel, Alix ; Gruel, Nadège

Dedifferentiated and Well-differentiated liposarcoma are characterized by a systematic amplification of the Murine Double Minute 2 (MDM2) oncogene. We demonstrate that p53-independent metabolic functions of chromatin-bound MDM2 are exacerbated in liposarcoma and mediate an addiction to serine metabolism to sustain tumor growth. However, the origin of exogenous serine remains unclear. Here, we show that elevated serine levels in mice harboring liposarcoma-patient derived xenograft, released by distant muscle is essential for liposarcoma cell survival. Repressing interleukine-6 expression, or treating liposarcoma cells with Food and Drugs Administration (FDA) approved anti-interleukine-6 monoclonal antibody, decreases de novo serine synthesis in muscle, impairs proliferation, and increases cell death in vitro and in vivo. This work reveals a metabolic crosstalk between muscle and liposarcoma tumor and identifies anti-interleukine-6 as a plausible treatment for liposarcoma patients.

2024-09-01·COMPUTERS IN BIOLOGY AND MEDICINE

Identification of critical genes and metabolic pathways in rheumatoid arthritis and osteoporosis toward drug repurposing

Article

作者: Ziaastani, Zahra ; Kalantari-Khandani, Behjat ; Niazi, Mohammad-Javad ; Kazemipour, Ali

BACKGROUND:

Rheumatoid arthritis (RA) and osteoporosis (OP) are considered to be complex diseases. In recent studies, a positive association between RA and OP has been reported triggering growing research interest. This study aims to investigate the drugs related to critical genes in RA and OP, using bioinformatics approaches, toward drug repurposing.

METHOD:

RA and OP genes were identified. The RA-OP PPI network was constructed and analyzed using the STRING and Cytoscape, respectively. Hub genes and modules were extracted and enriched Gene Ontology, through the WebGestalt and g:Profiler. The identification of the drugs related to critical genes using the DGIDB, and extracted the miRNAs using miRWalk and miRNet.

RESULTS:

By network clustering, five significant modules were obtained that have important roles in the immune system. IL6, TNF, IL1B, STAT3, TGFB1, TP53, HIF1A, CCL2, IL10, and MMP9 were found as the top 10 hub genes in the RA-OP network. Hub genes were shown to have implications in inflammatory response, significant functions in cytokine receptor binding, and localized mostly in extracellular space. By investigating the drugs related to hub genes, 16 drugs were identified as repurposing candidate drugs. The 10 drugs included Hydroxychloroquine, Infliximab, Adalimumab, Etanercept, Certolizumab, Cyclosporine, Diacerein, Gevokizumab, Canakinumab, and Olokizumab proposed for OP. Also, six drugs including Pirfenidone, Pentoxifylline, Vadimezan, Rilonacept, Metelimumab, and Siltuximab have important roles in inflammatory control and were proposed for both RA and OP.

CONCLUSIONS:

The results of the present study can provide novel insights into the pathogenesis and treatment of RA and OP.

项与司妥昔单抗相关的新闻（医药）

2024-10-18

·BiG生物创新社

盘点｜自免重磅靶点及研发进展

作者｜小麦目前自免是仅次于肿瘤的第二大市场领域，2022年全球自免药物市场规模约达1323亿美元，据弗若斯特沙利文预测，到2030年，全球自免药物市场规模有望达到1760亿美元，2022~2030年复合年增长率为3.6%。国内在自免领域远远落后于国外，但近几年国内自免药物发展迅速，今年迪哲医药的JAK抑制剂戈利昔替尼、康诺亚生物的IL-4Rα抗体药物司普奇拜单抗、恒瑞医药的靶向IL-17A生物制剂夫那奇珠单抗和智翔金泰的靶向IL-17A生物制剂赛立奇单抗等相继获批上市，有望打破进口药的垄断地位，给患者提供更多的选择。 01 JAK靶向制剂 JAK激酶属于细胞内非受体酪氨酸激酶家族，包括JAK1、JAK2、JAK3、TYK2四个成员，介导细胞因子产生的信号，并通过JAK-STAT信号通路传递下去，参与了免疫、细胞分裂、细胞死亡和肿瘤形成等过程。该通路异常可能导致各种疾病，如皮肤病、癌症和影响免疫系统的疾病等（图1）[1]。图1. JAK家族介导信号通路全球已有十多款JAK抑制剂获批上市，包括第一代的托法替布、芦可替尼、巴瑞替尼、培非替尼和迪高替尼；第二代的菲达替尼、乌帕替尼、非戈替尼、阿布昔替尼和帕瑞替尼以及第三代的氘可来昔替尼等，这些抑制剂大多用于关节炎、特应性皮炎等自免疾病（图2）。图2. 获批和部分在研的JAK抑制剂为了提高竞争力，很多药企开始探索JAK抑制剂的新用途，如辉瑞的利特昔替尼、礼来巴瑞替尼和Concert Pharmaceuticals/Sun Pharmaceuticals的氘代芦可替尼获批斑秃新适应症，迪哲医药的戈利昔替尼获批用于治疗既往至少接受过一线系统性治疗的复发或难治的外周T细胞淋巴瘤（r/r PTCL）成人患者，成为全球首个且唯一获批用于治疗PTCL的JAK1抑制剂。除此之外，还有很多临床在研的JAK抑制剂，如泽璟制药的杰克替尼、恒瑞医药的艾玛昔替尼、辉瑞/Priovant Therapeutics的brepocitinib和再极医药的MAX-40070等，其中杰克替尼和艾玛昔替尼都处于申报上市阶段。 02 IL-4靶向制剂白细胞介素4（IL-4）主要是由T细胞、自然T细胞、肥大细胞和嗜酸性粒细胞产生的一种糖基化的I型细胞因子。 IL-4和IL-13是2型免疫反应中的关键细胞因子，作用于1型 IL-4Rα/γ和/或2型IL-4Rα/IL-13Rα复合物引发其信号传导作用，从而激活JAK-STAT信号通路（图3）。图3. IL-4和IL-13介导的信号通路目前为止全球范围内有5款靶向IL-4R药物获批上市，分别是甲磺司特、度普利尤单抗、吡美莫司、Actimmune以及司普奇拜单抗，其中度普利尤单抗是全球首款获批的IL-4R单抗药物，司普奇拜单抗是国内首个、全球范围第二个申报并获批上市的IL-4Rα抗体药物。图4. 获批和部分在研的靶向IL-4的药物度普利尤单抗是赛诺菲的当家花旦，在自免领域尤其是特应性皮炎适应症上取得巨大成功，撑起特药板块半边天，2023年销售额达到107.15亿欧元（115.7亿美元）。今年7月和9月，度普利尤单抗相继在欧盟、美国和中国获批慢性阻塞性肺病（COPD）新适应症，扩大其适应人群。除此之外，临床上还有很多在研的IL-4/IL-4R抑制剂，如康乃德的CBP-201、康方生物的AK120以及智翔医药的GR-1802等。 03 IL-17靶向制剂白细胞介素17（IL-17）是由CD4+ T细胞分泌，能够诱导上皮细胞、内皮细胞、成纤维细胞合成分泌IL-6、IL-8、G-CSF、PGE2，促进ICAM-1的表达的促炎因子。 IL-17有 IL-17A、IL-17B、IL-17C、IL-17D、IL-17E（也被称为IL-25）和IL-17F 6个家族成员。白介素IL-17受体（IL-17R）有IL-17RA、IL-17RB、IL-17RC、IL-17RD、IL-17RE 5个家族成员（图5）[2]。图5. IL-17介导的信号通路全球范围内共上市7款靶向IL-17A/IL-17RA药物，分别是司库奇尤单抗、依奇珠单抗、尼塔奇单抗、比吉利珠单抗、布罗利尤单抗、夫那奇珠单抗和赛立奇单抗（图6）。图6. 获批和部分在研的靶向IL-17药物目前，司库奇尤单抗和依奇珠单抗是全球最畅销的两款IL-17靶向生物制剂，司库奇尤单抗是由诺华研发的首款获批上市的靶向IL-17A单抗，用于治疗银屑病、银屑病关节炎和强直性脊柱炎等自免疾病，2022年销售额达47.88亿美元，2023年销售额达49.8亿美元。依奇珠单抗是由礼来研发的靶向IL-17A单抗，是第一个在银屑病关节炎（PsA）头对头研究中疗效优于阿达木单抗的IL-17A拮抗剂，2022年销售额达到24.82亿美元，2023年销售额达到27.6亿美元。今年8月份，恒瑞医药的夫那奇珠单抗和智翔金泰的赛立奇单抗获批上市，用于治疗适合接受系统治疗或光疗的中重度斑块状银屑病成人患者，成为国产首批获批的本土自主研发重组抗IL-17A人源化单克隆抗体，将打破同类进口药物的长期垄断局面，为银屑病患者提供新的治疗选择。除此之外，还有很多临床在研的靶向IL-17的生物制剂，包括荃信生物的QX-002N，康方生物的AK-111和君实生物的JS005等。 04 IL-6靶向制剂白介素-6（IL-6）是趋化因子家族的一种细胞因子，主要由单核巨噬细胞、 Th2细胞、血管内皮细胞、成纤维细胞产生。 IL-6的受体蛋白，由特异性的IL-6结合受体蛋白（IL-6R），和被称为信号转导蛋白的gp130所组成。按照信号传导方式的差异，IL-6参与的信号途径，可以分为经典信号通路（classical signaling）和转信号通路（Trans-signaling）。在经典信号通路中，IL-6与其膜结合受体mIL-6R、可溶性受体sIL-6R结合后，招募gp130（一种跨膜蛋白，细胞因子受体）结合形成IL-6-IL-6R-gp130六聚体，触发下游JAK-STAT、RAS-RAF等信号通路转导和基因表达。在转信号通路中，IL-6-sIL-6R复合物与gp130结合，启动细胞内信号转导，促进细胞增殖、分化、氧化应激和免疫调节（图7）[3]。图7. IL-6信号转导和IL-6受体系统的模式 IL-6信号通路异常与很多疾病的发病机制有关，包括类风湿性关节炎（RA）、系统性幼年特发性关节炎(sJIA)、Castleman病、巨细胞动脉炎（GCA）、大动脉炎和细胞因子释放综合征（CRS）等。目前全球有4款药物获批上市，包括靶向IL-6R的托珠单抗、Sarilumab、和萨特利珠单抗以及靶向IL-6的司妥昔单抗，其中托珠单抗由于上市时间早应用广泛，销售额遥遥领先，受益于用于新冠治疗的获批，曾在2021年达到销售峰值39.6亿美元。图8. 部分靶向IL-6的药物除此之外，临床上还有很多在研的IL-6或IL-6R拮抗剂药物，为了提高竞争性，很多药企进行差异化布局，开发新的适应症，包括优时比的olokizumab、诺和诺德的ziltivekimab和罗氏的RG6179等（图6）。 Olokizumab最初由优时比公司研发，是一款靶向IL-6的人源化单抗。后来在2013年转让给了俄罗斯药企R-Pharm，目前正在进行RA领域的上市申请。 Ziltivekimab最初是由Corvidia Therapeutics研发的IL-6单抗药物，后于2020年6月，诺和诺德以21亿美元收购Corvidia Therapeutics，接管了其主要候选药物ziltivekimab的开发工作。 Ziltivekimab旨在阻断IL-6通路来降低全身炎症，从而降低动脉粥样硬化性心血管疾病（ASCVD）和慢性肾脏病（CKD）患者的主要心血管不良事件风险，具有延长的半衰期，可以通过每月一次皮下注射给药。 RG6179是由罗氏研发的IgG2类IL-6单抗，可阻断经典和转信号传导，用于糖尿病性黄斑水肿、自身炎症性疾病、黄斑水肿和葡萄膜性黄斑水肿。小结自免是一个很大的疾病领域，有很多疾病靶点，目前全球自身免疫病药物市场中，TNF-α和IL-12/IL-23两个自免领域老靶点抑制剂销售额仍位居前列，而JAK、IL-4R、IL-17A、IL-6、IL-5、URAT1、TSLP、MASP-2、TYK2等靶点，则吸引较多创新药企布局，本文主要介绍JAK、IL-4R、IL-17A和IL-6四个热门自免靶点及其研发进展。参考文献 1.Aikaterini Tsiogka et.al, The JAK/STAT Pathway and Its Selective Inhibition in the Treatment of Atopic Dermatitis: A Systematic Review, J. Clin. Med. 2022, 11, 4431 2.Mandy J. McGeachy, Daniel J. Cua, and Sarah L. Gaffen, The IL-17 Family of Cytokines in Health and Disease, Immunity 50, April 16, 2019 3.Masashi Narazaki and Tadamitsu Kishimoto, The Two-Faced Cytokine IL-6 in Host Defense and Diseases, Int. J. Mol. Sci. 2018, 19, 3528. BiG近期会议 10月26日，第三届生物计算大会保留栏目-第二届吐槽大会即将再度来袭！将围绕投融资、行业心态、年轻人，及AI等热门话题展开策划，通过移幕换景，大咖带新秀，一同探讨AI+Biomed的融合之道！ ▼ 10月31日，BiG联合Citeline，将于10月底，举办自免小规模私董研讨会，聚焦：TCE vs. CAR-T，自身免疫开发策略，线上同步直播，敬请期待！ ▼ 共建Biomedical创新生态圈！如何加入BiG会员？

上市批准免疫疗法细胞疗法

2024-10-18

·思路迪医药 3D Medicines

IF 40.8 | 梁廷波教授团队恩沃利单抗联合仑伐替尼和TACE治疗中晚期肝癌研究结果见刊！

基于经导管动脉化疗栓塞术（TACE）的联合治疗在不可切除肝细胞癌（uHCC）中的应用仍缺乏充分的可行性证据。近日，浙江大学医学院附属第一医院梁廷波教授团队在《Signal Transduction and Targeted Therapy》期刊发表了题为“Envafolimab plus lenvatinib and transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma: a prospective, single-arm, phase II study”的研究论文，梁廷波教授和白雪莉教授为通讯作者，该论文探讨了TACE联合恩沃利单抗和仑伐替尼治疗uHCC的疗效与安全性。研究背景肝细胞癌（HCC）是常见的恶性肿瘤之一，2022年其新发病例约占所有新发癌症病例的4.3%，死亡人数占所有癌症相关死亡人数的7.8%，死亡率在所有恶性肿瘤中排名第三[1]。然而，超过50%的HCC患者在确诊时已处于中晚期，预后较差，5年生存率仅为3%[2,3]。因此，通常建议进行全身治疗以实现肿瘤降期、转化治疗和长期生存[4,5]。 TACE是中晚期HCC一线治疗的可选方案，但反复进行TACE可能损害肝功能，并通过上调血管内皮生长因子（VEGF）的表达促进血管生成和肿瘤的远处转移，且大多数病例最终会复发[6,7,8]。TACTICS试验表明，TACE联合抗血管生成治疗可以显著延长uHCC患者的无进展生存期，显示出更好的治疗潜力，但其未能改善总生存期[9]。免疫检查点抑制剂（ICIs）近年来革新了癌症治疗。TACE治疗后，肿瘤坏死组织释放大量抗原，显著增加了CD4+和CD8+ T细胞数量，改善了免疫微环境，使得TACE联合免疫治疗能触发更强烈的肿瘤特异性免疫反应，显著提升治疗效果[10]。恩沃利单抗作为首个皮下注射的抗PD-L1抗体，已在晚期实体瘤中展现出良好疗效[11,12]，有望在中晚期HCC中发挥疗效，革新HCC的治疗模式。因此，本研究评估恩沃利单抗联合仑伐替尼和TACE治疗uHCC的疗效和安全性，为中晚期HCC提供新的治疗策略。研究设计这是一项前瞻性、开放标签、单臂II期研究，在2022年3月至2022年7月期间，共纳入38例患者参与本研究。纳入标准如下：(1) 年龄在18至75岁之间；(2) 影像学、组织学或细胞学证实的HCC（基于美国肝病研究学会（AASLD）标准）；(3) 巴塞罗那肝癌分期（BCLC）B期或C期；(4) 经肝胆胰多学科团队（MDT）确认的uHCC；(5) 至少有一个可测量病灶（根据RECIST1.1标准）；(6) 未接受过全身性抗肿瘤治疗；(7) ECOG-PS评分为0-1；(8) Child-Pugh评分≤7分；(9) 器官功能正常，预期生存期至少3个月。患者从首次TACE开始，接受恩沃利单抗（300 mg，皮下注射，每三周一次）和仑伐替尼（≥60kg：12mg，<60kg：8mg，每日口服）联合治疗，直至疾病进展、转化为可手术、无法耐受的毒性、撤回知情同意或死亡。主要终点为客观缓解率（ORR），次要终点为疾病控制率（DCR）、缓解持续时间（DoR）、无进展生存期（PFS）以及总生存期（OS）。其他终点包括手术转化率、病理完全缓解率（pCR）、R0切除率、主要病理反应（MPR）和无病生存期（DFS）。研究结果 1 基线特征共纳入38例患者进行分析，基线特征如下：年龄中位数为55.5岁（95%CI：28-73），男性占81.6%。CNLC IIa、IIb、IIIa、IIIb期患者人数分别为4（10.5%）、13（34.2%）、18（47.4%）、3（7.9%）例，BCLC B期、C期患者人数分别为17（44.7%）、21（55.3%）例。14例（36.8%）患者伴有门静脉癌栓（PVTT），5例（13.2%）患者伴有肝静脉癌栓（HVTT）。所有患者的Child-Pugh评分均为A类，其中94.7%得分为5分，5.3%得分为6分。中位ALBI评分为-2.78（95%CI：-3.44 - -2.03）。3例（7.9%）患者伴有肝外转移，7例（18.4%）患者曾接受过治疗，其中3例（7.9%）接受过手术，4例（10.5%）接受过TACE。表1 患者基线特征 2 临床结局共36例患者进入疗效分析集。截至2023年12月13日，中位随访时间为16.9个月（IQR，14.8–18.1）。根据RECIST1.1标准，ORR、DCR分别为50%（95%CI：32.9–67.1%）、83.3%（95%CI：67.2–93.6%），中位DoR为6.8个月（95% CI：2.77-NA）。根据mRECIST标准，ORR和DCR均为83.3%（95%CI：67.2–93.6%）,中位DoR为8.12个月（95% CI：4.9-NA）。根据RECIST 1.1或mRECIST标准，mPFS为7.58个月（95% CI：5.1-16.1），mOS为19.9个月（95% CI：18.2-NA），1年总生存率为88.9%（95% CI：79.2–99.8%）。此外，17例患者转化为可切除的HCC，手术转化率为47.2%，其中16例患者接受了手术，R0切除率为100%，pCR率为31.3%。术后预后方面，达到pCR的患者1年无病生存率显著优于未达到pCR的患者（100%vs36.4%；P< 0.05）。术后随访仍在进行中，术后预后的结果将在未来进一步更新。图1 肿瘤反应和生存结局。 (a) 根据RECIST 1.1标准的目标病灶大小从基线开始的最佳变化的瀑布图；(b) 根据mRECIST标准的目标病灶大小从基线开始的最佳变化的瀑布图；(c) PFS的Kaplan–Meier曲线；(d) OS的Kaplan–Meier曲线。CR：完全缓解，PR：部分缓解，SD：疾病稳定，PD：疾病进展。 3 安全性分析 37（97.4%）例患者出现治疗相关不良事件（TRAEs），其中20（52.6%）例患者出现≥3级的TRAEs。最常见的≥3级的TRAEs为天冬氨酸氨基转移酶（AST）升高（34.2%）、丙氨酸氨基转移酶（ALT）升高（18.4%）以及血小板计数减少（15.8%）。只有1例（2.6%）患者出现严重不良事件（SAE；胃肠道出血），未发生与治疗相关的死亡。表2治疗相关不良事件讨论与结论这是首个评估恩沃利单抗联合靶向治疗和TACE在uHCC治疗中可行性的II期研究。研究结果表明，该联合疗法具有良好的疗效和安全性，且具有较高的手术转化率和pCR率，为中晚期uHCC患者提供了新的治疗选择。该联合疗法基于RECIST 1.1标准（50%）和mRECIST标准（83.3%）的肿瘤应答率均显著高于其他多项研究：无论是在总人群（47.4% vs. 30%），还是BCLC B期（94.12% vs.44%）或C期患者（66.67% vs.27%）中，均优于同样探讨免疫检查点抑制剂联合抗血管生成药物对HCC的疗效的IMbrave150试验[13,14]，表明联合恩沃利单抗的疗法在不同人群中均有较高应答率，不仅适用于中期患者，也有潜力作为晚期uHCC转化治疗方案。此外，本研究中手术转化切除率达47.2%，且术后病理结果良好，显示出其显著的可行性。在安全性方面，该联合疗法AE谱与各药物一致[15,16]，表现出良好的安全性。本研究未观察到输液反应，这可能得益于恩沃利单抗采用皮下注射方式。相较于其他PD-1/PD-L1抑制剂的静脉注射，皮下注射方式更具便捷性和耐受性。未来，将进一步验证该联合疗法对长期生存的影响。同时，对于可能影响生存率的因素，如TKI、PD-1/PD-L1抗体的种类，及TACE技术，未来仍需进一步探讨。总之，恩沃利单抗联合仑伐替尼和TACE在uHCC的治疗中表现出了良好的疗效、手术转化率及安全性，为uHCC患者的治疗提供了新的有价值的治疗选择。仅供医疗卫生专业人士阅读转载自：SIMMED 参考文献： [1] BRAY F, LAVERSANNE M, SUNG H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J]. CA Cancer J Clin, 2024, 74(3): 229-263. [2] SIEGEL R L, MILLER K D, FUCHS H E, et al. Cancer statistics, 2022 [J]. CA Cancer J Clin, 2022, 72(1): 7-33. [3] REIG M, FORNER A, RIMOLA J, et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update [J]. J Hepatol, 2022, 76(3): 681-693. [4] SUN H C, ZHU X D. Downstaging Conversion Therapy in Patients With Initially Unresectable Advanced Hepatocellular Carcinoma: An Overview [J]. Front Oncol, 2021, 11: 772195. [5] GUO C, ZHANG J, HUANG X, et al. Preoperative sintilimab plus transarterial chemoembolization for hepatocellular carcinoma exceeding the Milan criteria: A phase II trial [J]. Hepatol Commun, 2023, 7(3): e0054. [6] BROWN Z J, TSILIMIGRAS D I, RUFF S M, et al. Management of Hepatocellular Carcinoma: A Review [J]. JAMA Surg, 2023, 158(4): 410-420. [7] SERGIO A, CRISTOFORI C, CARDIN R, et al. Transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC): the role of angiogenesis and invasiveness [J]. Am J Gastroenterol, 2008, 103(4): 914-921. [8] LENCIONI R, DE BAERE T, SOULEN M C, et al. Lipiodol transarterial chemoembolization for hepatocellular carcinoma: A systematic review of efficacy and safety data [J]. Hepatology, 2016, 64(1): 106-116. [9] KUDO M, UESHIMA K, IKEDA M, et al. Randomised, multicentre prospective trial of transarterial chemoembolisation (TACE) plus sorafenib as compared with TACE alone in patients with hepatocellular carcinoma: TACTICS trial [J]. Gut, 2020, 69(8): 1492-1501. [10] GRETEN T F, MAUDA-HAVAKUK M, HEINRICH B, et al. Combined locoregional-immunotherapy for liver cancer [J]. J Hepatol, 2019, 70(5): 999-1007. [11] MARKHAM A. Envafolimab: First Approval [J]. Drugs, 2022, 82(2): 235-240. [12] LI J, DENG Y, ZHANG W, et al. Subcutaneous envafolimab monotherapy in patients with advanced defective mismatch repair/microsatellite instability high solid tumors [J]. J Hematol Oncol, 2021, 14(1): 95. [13] LI Q, CAO M, YUAN G, et al. Lenvatinib Plus Camrelizumab vs. Lenvatinib Monotherapy as First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Multicenter Retrospective Cohort Study [J]. Front Oncol, 2022, 12: 809709. [14] CHENG A L, QIN S, IKEDA M, et al. Updated efficacy and safety data from IMbrave150: Atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma [J]. J Hepatol, 2022, 76(4): 862-873. [15] ZHU Y, SUN P, WANG K, et al. Efficacy and safety of lenvatinib monotreatment and lenvatinib-based combination therapy for patients with unresectable hepatocellular carcinoma: a retrospective, real-world study in China [J]. Cancer Cell Int, 2021, 21(1): 503. [16] ABOU-ALFA G K, MEYER T, CHENG A L, et al. Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma [J]. N Engl J Med, 2018, 379(1): 54-63.

临床结果临床2期

2024-10-11

·GlobeNewswire-Health Care

Tourmaline Bio to Showcase Two Poster Presentations at the 2024 Cardiometabolic Health Congress

NEW YORK, Oct. 11, 2024 (GLOBE NEWSWIRE) -- Tourmaline Bio, Inc. (Tourmaline) (NASDAQ: TRML), a late-stage clinical biotechnology company developing transformative medicines to dramatically improve the lives of patients with life-altering immune and inflammatory diseases, today announced that it expects to present two posters at the upcoming 19th Annual Cardiometabolic Health Congress (CMHC), taking place October 17-19, 2024, in Boston, MA. These posters highlight Tourmaline's ongoing commitment to further characterizing inflammatory cardiovascular risk, as well as potential therapeutic mechanisms of IL-6 inhibition. Poster Presentations:Title: Utilization of High-Sensitivity C-Reactive Protein Testing in Primary and Secondary ASCVD PreventionAuthors: Emil deGoma, MD1; Yung Chyung, MD1; John Walsh, MD1; C. William Pike, MD2; Jananee Muralidharan, MD2; Vincent Marino2; J. Craig Davis2; Saurabh Gombar, MD, PhD2; Michael D. Shapiro, DO, MCR3Affiliations: 1Tourmaline Bio, Inc., New York, NY, USA2Atropos Health, Inc., New York, NY, USA 3Wake Forest University School of Medicine, Winston-Salem, NC, USA Title: Effect of IL-6 Inhibition on Lipoprotein(a) Levels: A Systematic Review and Meta-AnalysisAuthors: Saeid Mirzai, DO1; Emil deGoma, MD2; John Walsh, MD2; Raya Mahbuba, MSc3; Yung Chyung, MD2; Michael D. Shapiro, DO, MCR1Affiliations: 1Wake Forest University School of Medicine, Winston-Salem, NC, USA2Tourmaline Bio, Inc., New York, NY, USA3Independent researcher, Toronto, ON, Canada For more information, please visit https://www.cardiometabolichealth.org/19th-annual-cmhc/. About Tourmaline BioTourmaline is a late-stage clinical biotechnology company driven by its mission to develop transformative medicines that dramatically improve the lives of patients with life-altering immune and inflammatory diseases. Tourmaline’s lead asset is pacibekitug (also referred to as TOUR006). About PacibekitugPacibekitug (also referred to as TOUR006) is a long-acting, fully-human, anti-IL-6 monoclonal antibody with best-in-class potential and differentiated properties including a naturally long half-life, low immunogenicity, and high binding affinity to IL-6. Pacibekitug has been previously studied in approximately 450 participants, including patients with autoimmune disorders, across six completed clinical trials. Tourmaline is developing pacibekitug in thyroid eye disease (TED) and atherosclerotic cardiovascular disease (ASCVD) as its first two indications, with additional diseases under consideration. For more information about Tourmaline Bio and pacibekitug, please visit https://www.tourmalinebio.com. Media ContactScient PRSarah MishekSMishek@ScientPR.com Investor ContactMeru AdvisorsLee M. Sternlstern@meruadvisors.com

100 项与司妥昔单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D09669	司妥昔单抗	L04AC11	DB09036

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
多中心Castleman病	美国	EUSA Pharma (UK) Ltd.	2014-04-23
多中心Castleman病	美国	Recordati Rare Diseases, Inc.	2014-04-23

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
Castleman病	申请上市	中国	-	2021-01-20
肺炎	临床3期	美国	EUSA Pharma (UK) Ltd.	2020-11-13
急性呼吸窘迫综合征	临床3期	美国	EUSA Pharma (UK) Ltd.	2020-11-13
浆细胞骨髓瘤难治	临床3期	美国	Centocor, Inc.	2011-07-01
浆细胞骨髓瘤难治	临床3期	澳大利亚	Centocor, Inc.	2011-07-01
浆细胞骨髓瘤难治	临床3期	比利时	Centocor, Inc.	2011-07-01
浆细胞骨髓瘤难治	临床3期	保加利亚	Centocor, Inc.	2011-07-01
浆细胞骨髓瘤难治	临床3期	加拿大	Centocor, Inc.	2011-07-01
浆细胞骨髓瘤难治	临床3期	捷克	Centocor, Inc.	2011-07-01
浆细胞骨髓瘤难治	临床3期	印度	Centocor, Inc.	2011-07-01

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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


NCT04191421 (AACR2024) 人工标引	临床1/2期	晚期胰腺腺癌	-	Siltuximab 6 mg/kg	鑰鏇顧窪憲鏇鏇蓋壓憲(製選獵鹹積廠餘鹽選築) = 願獵顧製構選襯願蓋鹽襯簾繭構憲衊範憲構積 (積憲餘簾網膚窪鹹壓積 ) 更多	积极	2024-04-05
NCT04191421 (AACR2024) 人工标引	临床1/2期	晚期胰腺腺癌	-	Siltuximab 11 mg/kg	鑰鏇顧窪憲鏇鏇蓋壓憲(製選獵鹹積廠餘鹽選築) = 願觸鹽艱窪壓選鑰膚鹽襯簾繭構憲衊範憲構積 (積憲餘簾網膚窪鹹壓積 ) 更多	积极	2024-04-05
Tandem Meetings ASTCT and CIBMTR2024 人工标引	N/A	血液肿瘤	-	Siltuximab	鏇壓醖鬱壓艱淵獵憲憲(糧願淵範襯鏇鹹遞糧觸) = 鏇觸鏇築獵廠範築窪範構鬱願簾夢網築網願襯 (窪網衊製齋觸範壓遞艱 ) 更多	积极	2024-02-01
Tandem Meetings ASTCT and CIBMTR2024 人工标引	临床1期	B细胞淋巴瘤	11	Siltuximab	憲衊夢鹹鏇艱壓觸鹽範(齋選積淵餘襯顧鹽壓夢) = 網積願艱夢範餘觸鹽選鹹網鑰窪憲鑰齋選齋構 (選鬱願獵蓋願鬱觸遞窪 ) 更多	积极	2024-02-01
ASH2023	N/A	-	52	Siltuximab	構鑰獵壓窪繭簾淵鏇願(壓築鹹夢膚夢餘鏇願築) = 膚遞憲襯積繭蓋鏇襯簾構醖壓壓鹹廠齋衊網選 (範壓糧餘齋鑰醖鏇壓廠 )	-	2023-12-11
ASCO2023	N/A	Castleman病	40	Siltuximab	簾範廠繭鑰窪膚夢願夢(膚願鹹鏇築廠艱壓鬱鬱) = 網鑰網膚廠網顧積鬱鏇鏇積壓膚積鹹鏇製淵膚 (遞鏇範鏇餘選網顧襯觸, 59.7)	积极	2023-05-31
EBMT2023	N/A	细胞因子释放综合征 Interleukin-6 (IL6) receptor \| interleukin-1 (IL1)	-	Anakinra	遞齋顧夢艱艱鹹糧憲衊(鹽遞廠壓積繭糧繭壓衊) = 廠鹽獵艱蓋鬱蓋衊願製齋鏇醖鑰壓繭製顧鹹廠 (蓋艱鬱願獵獵繭觸廠襯 ) 更多	-	2023-04-23
NCT04975555 (Phase 2 Trial of Siltuximab, Tandem Meetings ASTCT and CIBMTR2023)	临床2期	神经中毒综合征 \| 细胞因子释放综合征	6	Siltuximab 11mg/kg	鏇願壓製膚衊構憲範壓(繭簾艱遞鹹餘襯醖願鑰) = 1 pt who did not respond to siltuximab and received rescue tocilizumab for persistent CRS grade 2 required ICU transfer for ICANS grade 3 壓願憲簾齋簾願構鹹夢 (獵襯鏇憲顧餘網獵網鏇 ) 更多	积极	2023-02-01
NCT01024036 (EHA2022)	临床2期	多中心Castleman病	79	Siltuximab	窪繭廠簾鹽積憲構憲襯(顧鑰衊觸願網蓋夢製網) = 製襯鑰構壓鑰衊壓構齋衊窪壓餘艱鹽壓鹽積廠 (鬱艱構網網襯壓壓鏇範 ) 更多	-	2022-05-12
NCT01024036 (EHA2022)	临床2期	多中心Castleman病	79	Placebo	窪繭廠簾鹽積憲構憲襯(顧鑰衊觸願網蓋夢製網) = 選範壓鹹觸蓋淵艱鹽齋衊窪壓餘艱鹽壓鹽積廠 (鬱艱構網網襯壓壓鏇範, 13.6 ~ upper bound not reached) 更多	-	2022-05-12
ARVO2021	N/A	视网膜疾患	8	Anti-Interleukin-6 Monoclonal Antibodies	艱艱艱衊鬱衊顧餘鹽鹹(鑰鹹範膚廠願願獵築廠) = 窪衊築膚餘鏇鹹鹽餘襯襯築鬱繭淵鬱廠鏇壓廠 (膚鬱窪願簾鏇鹽顧衊繭 ) 更多	-	2021-06-01
NCT01400503 (Pubmed \| Lancet Haematol) 人工标引	临床2期	多中心Castleman病	60	Siltuximab	餘製窪艱衊窪廠簾築鹹(鏇鹹鏇鹽鹹範鹹製鹹壓) = 憲壓艱繭鏇糧膚鬱鏇鏇鹽窪網醖醖積膚築鬱願 (艱艱選醖築顧遞構淵窪 ) 更多	积极	2020-03-01