A phase Ib/II multi-center, open label, dose escalation study of WNT974, LGX818 and cetuximab in patients with BRAFV600-mutant metastatic colorectal cancer harboring Wnt pathway mutations

开始日期2014-12-18

申办/合作机构

Array BioPharma, Inc.

NCT02278133 / Completed临床1/2期

A Phase Ib/II Multi-center, Open Label, Dose Escalation Study of WNT974, LGX818 and Cetuximab in Patients With BRAFV600-mutant KRAS Wild-type Metastatic Colorectal Cancer Harboring Wnt Pathway Mutations

The purpose of this study is to assess the safety and anti-tumor activity of the triple combination of WNT974, LGX818 and cetuximab in BRAFV600-mutant mCRC with RNF43 mutations or RSPO fusions.
The design of this study is based upon the translational and pre-clinical data that suggest that Wnt pathway signals, increased due to RNF43 mutations or RSPO fusions, cooperate with the EGFR and BRAF signals to maintain the growth of BRAFV600 CRCs. Inhibition of these signals with the triple combination of WNT974, LGX818 and cetuximab may result in anti-tumor activity.

开始日期2014-12-01

申办/合作机构

Array BioPharma, Inc.

NCT01351103 / Active, not recruiting临床1期

A Phase I, Open-label, Dose Escalation Study of Oral LGK974 in Patients With Malignancies Dependent on Wnt Ligands

The primary purpose of this study is to find the recommended dose of LGK974 as a single agent and in combination with PDR001 that can be safely given to adult patients with selected solid malignancies that have progressed despite standard therapy or for which no effective standard therapy exists

开始日期2011-12-01

申办/合作机构

Novartis Pharmaceuticals Corp.

100 项与 LGK-974 相关的临床结果

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100 项与 LGK-974 相关的转化医学

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100 项与 LGK-974 相关的专利（医药）

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项与 LGK-974 相关的文献（医药）

2023-12-30·International immunopharmacology

LGK974 suppresses the formation of deep vein thrombosis in mice with sepsis.

Article

作者: Zhishu Li ; Xiaoxi Shan ; Guolin Yang ; Lixia Dong

BACKGROUND:

Sepsis is a disorder characterized by host inflammation and is caused by systemic infection. The inflammatory cytokine storm results in platelet overactivation, leading to coagulation dysfunction and thrombosis, but the underlying mechanism remains poorly understood. Recent evidence has shown that the Wnt/β-catenin signaling pathway is related to sepsis, but its role and mechanism in sepsis complicated with deep vein thrombosis (DVT) are unclear.

METHODS:

In this study, a cecal ligation and puncture (CLP)-induced sepsis model and DVT mouse model were constructed by inferior vena cava ligation. The levels of serum inflammatory factors and adhesion molecules were measured in each group, and the thrombus weight and size, hematoxylin-eosin staining, collagen fiber tissue, and transcriptome of the venous wall were analyzed. The activation of the Wnt/β-catenin signal was evaluated by quantitative real-time polymerase chain reaction, Western blotting, ELISA, and immunohistochemical and immunofluorescence methods.

RESULTS:

Sepsis significantly promoted the formation of venous wall collagen fibers and DVT. In addition, Porcn significantly upregulated and activated the Wnt/β-catenin signaling pathway in sepsis mouse models with DVT. In contrast, the Wnt signaling inhibitor LGK974 was found to improve the survival rate, decrease thrombosis, and inhibit the expression of inflammation and adhesion molecules in sepsis mice with DVT. Therefore, activation of the Wnt/β-catenin signal may promote the formation of DVT in sepsis mice.

CONCLUSIONS:

LGK974 protects against DVT formation in sepsis mice by inhibiting the activation of the Wnt/β-catenin signal and down-regulating the production of proinflammatory cytokines, PAI-1, and adhesion molecules. LGK974 may be a new candidate for the treatment of sepsis complicated with DVT.

2023-05-23·bioRxiv : the preprint server for biology

Suppression of tumor cell lactate-generating signaling pathways eradicates murine PTEN/p53-deficient aggressive-variant prostate cancer via macrophage phagocytosis.

作者: Kiranj Chaudagar ; Hanna M Hieromnimon ; Anne Kelley ; Brian Labadie ; Jordan Shafran ; Srikrishnan Rameshbabu ; Catherine Drovetsky ; Kaela Bynoe ; Ani Solanki ; Erica Markiewicz ; Xiaobing Fan ; Massimo Loda ; Akash Patnaik

Purpose:

PTEN loss-of-function/PI3K pathway hyperactivation occurs in ∼50% of metastatic, castrate-resistant prostate cancer patients, resulting in poor therapeutic outcomes and resistance to immune checkpoint inhibitors across multiple malignancies. Our prior studies in prostate-specific PTEN/p53-deleted genetically engineered mice (Pb-Cre;PTEN ^fl/fl Trp53 ^fl/fl GEM) with aggressive-variant prostate cancer (AVPC) demonstrated feedback Wnt/β-catenin signaling activation in 40% mice resistant to androgen deprivation therapy (ADT)/PI3K inhibitor (PI3Ki)/PD-1 antibody (aPD-1) combination, resulting in restoration of lactate cross-talk between tumor-cells and tumor-associated macrophages (TAM), histone lactylation (H3K18lac) and phagocytic suppression within TAM. Here, we targeted immunometabolic mechanism(s) of resistance to ADT/PI3Ki/aPD-1 combination, with the goal of durable tumor control in PTEN/p53-deficient PC.

Experimental design:

Pb-Cre;PTEN ^fl/fl Trp53 ^fl/fl GEM were treated with either ADT (degarelix), PI3Ki (copanlisib), aPD-1, MEK inhibitor (trametinib) or Porcupine inhibitor (LGK 974) as single agents or their combinations. MRI was used to monitor tumor kinetics and immune/proteomic profiling/ ex vivo co-culture mechanistic studies were performed on prostate tumors or established GEM-derived cell lines.

Results:

We tested whether Wnt/β-catenin pathway inhibition with LGK 974 addition to degarelix/copanlisib/aPD-1 therapy enhances tumor control in GEM, and observed de novo resistance due to feedback activation of MEK signaling. Based on our observation that degarelix/aPD-1 treatment resulted in partial inhibition of MEK signaling, we substituted trametinib for degarelix/aPD-1 treatment, and observed a durable tumor growth control of PI3Ki/MEKi/PORCNi in 100% mice via H3K18lac suppression and complete TAM activation within TME.

Conclusions:

Abrogation of lactate-mediated cross-talk between cancer cells and TAM results in durable ADT-independent tumor control in PTEN/p53-deficient AVPC, and warrants further investigation in clinical trials.

STATEMENT OF TRANSLATIONAL RELEVANCE:

PTEN loss-of-function occurs in ∼50% of mCRPC patients, and associated with poor prognosis, and immune checkpoint inhibitor resistance across multiple malignancies. Our prior studies have demonstrated that ADT/PI3Ki/PD-1 triplet combination therapy controls PTEN/p53-deficient PC in 60% of mice via enhancement of TAM phagocytosis. Here, we discovered that resistance to ADT/PI3K/PD-1 therapy occurred via restoration of lactate production via feedback Wnt/MEK signaling following treatment with PI3Ki, resulting in inhibition of TAM phagocytosis. Critically, co-targeting of PI3K/MEK/Wnt signaling pathways using an intermittent dosing schedule of corresponding targeted agents resulted in complete tumor control and significantly prolonged survival without significant long-term toxicity. Collectively, our findings provide "proof-of-concept" that targeting lactate as a macrophage phagocytic checkpoint controls growth of murine PTEN/p53-deficient PC and warrant further investigation in AVPC clinical trials.

2023-04-12·Circulation research

Targeting Wnt-ß-Catenin-FOSL Signaling Ameliorates Right Ventricular Remodeling.

Article

作者: Sreenath Reddy Nayakanti ; Aleksandra Friedrich ; Poonam Sarode ; Leili Jafari ; Giovanni Maroli ; Mario Boehm ; Alice Bourgeois ; Yann Grobs ; Fatemeh Khassafi ; Carsten Kuenne ; Stefan Guenther ; Swati Dabral ; Jochen Wilhelm ; Astrid Weiss ; Astrid Wietelmann ; Baktybek Kojonazarov ; Wiebke Janssen ; Mario Looso ; Frances de Man ; Steeve Provencher ; Khodr Tello ; Werner Seeger ; Sebastien Bonnet ; Rajkumar Savai ; Ralph T Schermuly ; Soni Savai Pullamsetti

BACKGROUND:

The ability of the right ventricle (RV) to adapt to an increased pressure afterload determines survival in patients with pulmonary arterial hypertension. At present, there are no specific treatments available to prevent RV failure, except for heart/lung transplantation. The wingless/int-1 (Wnt) signaling pathway plays an important role in the development of the RV and may also be implicated in adult cardiac remodeling.

METHODS:

Molecular, biochemical, and pharmacological approaches were used both in vitro and in vivo to investigate the role of Wnt signaling in RV remodeling.

RESULTS:

Wnt/β-catenin signaling molecules are upregulated in RV of patients with pulmonary arterial hypertension and animal models of RV overload (pulmonary artery banding-induced and monocrotaline rat models). Activation of Wnt/β-catenin signaling leads to RV remodeling via transcriptional activation of FOSL1 and FOSL2 (FOS like 1/2, AP-1 [activator protein 1] transcription factor subunit). Immunohistochemical analysis of pulmonary artery banding -exposed BAT-Gal reporter mice RVs exhibited an increase in β-catenin expression compared with their respective controls. Genetic inhibition of β-catenin, FOSL1/2, or WNT3A stimulation of RV fibroblasts significantly reduced collagen synthesis and other remodeling genes. Importantly, pharmacological inhibition of Wnt signaling using LGK-974 attenuated fibrosis and cardiac hypertrophy leading to improvement in RV function in both, pulmonary artery banding - and monocrotaline-induced RV overload.

CONCLUSIONS:

Wnt- β-Catenin-FOSL signaling is centrally involved in the hypertrophic RV response to increased afterload, offering novel targets for therapeutic interference with RV failure in pulmonary hypertension.

项与 LGK-974 相关的新闻（医药）

2023-04-13

·生物谷

Sci Transl Med：科学家识别出能克服三阴性乳腺癌对疗法耐受性的新型潜在靶点

来自迈阿密大学米勒医学院等机构的科学家们通过研究发现，不成熟的自然杀伤性细胞或许存在于三阴性乳腺癌患者机体中，并且可能会促进（并非抑制）这种类型癌症的进展。自然杀伤性细胞（NK cells）是一种细胞毒性淋巴细胞，其会在肿瘤微环境中积累，通常被认为具有一定的抗肿瘤特性。近日，一篇发表在国际杂志Science Translational Medicine上题为“Immature natural killer cells promote progression of triple-negative breast cancer”的研究报告中，来自迈阿密大学米勒医学院等机构的科学家们通过研究发现，不成熟的自然杀伤性细胞或许存在于三阴性乳腺癌患者机体中，并且可能会促进（并非抑制）这种类型癌症的进展。相关研究结果或有望帮助研究人员通过确定特定的NK细胞作为潜在的治疗性靶点，从而抵御三阴性乳腺癌（一种最具侵袭性的乳腺肿瘤）患者对疗法的耐受性。 NK细胞通常被认为是机体抗肿瘤免疫反应的有效促进者，然而，并非所有的NK细胞都是平等的，研究者表示，不成熟的NK细胞或许存在于三阴性乳腺癌患者的组织样本中，且与这一类患者亚群的疾病预后较差有关。乳腺癌是一种最常被诊断的人类癌症，其目前仍然是引发美国女性癌症相关死亡的第二大原因，仅在2020年就有大约27.5万多例新发病例。三阴性乳腺癌在所有乳腺癌中占到了10%-15%的病例，其主要特点为缺失雌激素和孕激素受体，以及名为人类表皮生长因子（HER2）的特殊蛋白；相比其它类型的乳腺癌而言，三阴性乳腺癌患者有着较高的癌症复发率和转移率，而且由于缺少激素受体和HER2蛋白作为治疗性靶点，目前并没有有效的疗法来治疗这类乳腺癌患者。科学家识别出能克服三阴性乳腺癌对疗法耐受性的新型潜在靶点。图片来源：Science Translational Medicine (2023). DOI:10.1126/scitranslmed.abl4414 据美国癌症协会数据显示，三阴性乳腺癌通常会影响40岁以下的女性、黑人女性以及携带BRCA1基因突变的女性。为此，这项研究中，研究者Chakrabarti等人就通过研究利用强大的RNA测序技术在单细胞水平上对患者机体的组织样本进行研究区分其细胞变异，从而就能识别出这些行为失常的NK细胞。传统上来讲，研究人员能利用大量的RNA测序来进行这种识别过程，但这种方法或许会错过肿瘤微环境中特殊的NK细胞。研究人员还利用一种创新性的小鼠模型进行研究发现，NK细胞会促进而不是阻止小鼠机体中肿瘤的进展，通过剔除这些细胞或抑制来自NK细胞的Wnt配体分泌来防止促进基因破坏和癌症发生的错误细胞信号，研究人员就能在小鼠机体中有效阻断这种效应，这或许就表明，不成熟的NK细胞或许能作为三阴性乳腺癌患者的一种潜在的治疗性靶点。研究者解释道，本文研究对于三阴性乳腺癌患者或许有望改变“游戏规则”，对免疫疗法或化疗的耐受性或许会给这些患者带来很大的问题，因为其中很少有患者会对当前疗法产生良好的反应，而找到更好的药物靶点对于提高患者的生存率至关重要。这项研究或许就能为实现这一目标铺平道路，在研究者所开发的小鼠模型中，阻断未成熟的NK细胞就会使得肿瘤对化疗与免疫疗法的组合性疗法变得敏感，这或许就能为开发有效的疗法开辟新的路径。目前研究者Chakrabarti及其同事正在重点分析在侵袭性三阴性乳腺癌患者机体的肿瘤微环境中，行为失常的NK细胞是如何产生的以及其如何与其它免疫细胞相互作用；研究人员正在分析利用FDA批准的药物LGK-974来促使肿瘤细胞对化疗和免疫疗法变得敏感，从而导致新的以及更好的治疗效果。综上，本文研究中，研究人烟识别出了一种特殊的促癌NK细胞群，其或许有望被用来开发特殊的诊断和治疗性策略来改善三阴性乳腺癌患者的治疗结局。（生物谷Bioon.com）原始出处： GATHA THACKER,SAMANTHA HENRY,AJEYA NANDI, et al. Immature natural killer cells promote progression of triple-negative breast cancer, Science Translational Medicine (2023). DOI: 10.1126/scitranslmed.abl4414

细胞疗法临床研究

2023-03-17

·药明康德

前沿 |《科学》子刊：三阴性乳腺癌治疗新策略——靶向这种免疫细胞

乳腺癌是最为常见的癌症类型，2020年的一项最新统计显示，当年全球约新增230万名乳腺癌患者，造成68.5万名患者死亡。其中，三阴性乳腺癌（TNBC）是乳腺癌最具侵袭性的分子亚型之一，占所有乳腺癌病例的10%-15%，其特征是缺乏雌激素和孕酮受体（ER/PR）以及缺乏人表皮生长因子受体-2（HER2）。与其他乳腺癌亚型相比，TNBC患者往往更易出现复发和转移，导致预后不良。同时，由于ER、PR和HER2的表达水平较低，这类患者对于内分泌治疗和常用的靶向疗法都不敏感，TNBC患者的个体差异和肿瘤的分子异质性为“通用型”靶向疗法的开发带来了不小的挑战。图片来源：123RF科学家们转而将目光放在TNBC的肿瘤微环境（TME）中，其中存在着大量的肿瘤浸润性免疫细胞。既往研究发现这些细胞对于肿瘤进展有着重要的影响，甚至其表型分析具有指示TNBC预后的效用，凸显了这些细胞作为TNBC患者免疫治疗靶点的潜力。其中，自然杀伤（NK）细胞是细胞毒性淋巴细胞，可以识别并消除肿瘤细胞，因此被认为是对肿瘤的早期反应者，它的存在也与多种癌症的治疗结局有着密切关联。最近，宾夕法尼亚大学（University of Pennsylvania）的研究团队利用单细胞RNA测序技术和功能分析针对TNBC肿瘤微环境中的NK细胞展开了研究，详细分析了它的细胞组成和功能，并探讨了潜在的治疗策略。研究结果已整理发表于《科学》杂志子刊Science Translational Medicine上。研究人员选择了TNBC小鼠作为研究模型，这类小鼠的肿瘤具有高度自发性转移的特征。他们首先通过CD45抗体来区分TME中的免疫细胞（CD45+）和非免疫细胞（CD45-，如肿瘤细胞、纤维母细胞）。单细胞RNA测序分析表明，TNBC小鼠肿瘤中上皮间质转化、糖酵解以及缺氧相关的标志物表达水平升高，并且TME呈现出免疫抑制性特征，这些发现和以往报道相一致。此外，CD45-细胞亚群模拟了人类TNBC肿瘤的异质性和侵袭性特征，进一步验证了该模型用于研究TNBC肿瘤微环境的可行性。 CD45+免疫细胞共包含了15种不同的细胞亚群，其中，Nkg7阴性（Nkg7-）的NK细胞和NKT细胞在高度转移性/非转移性TNBC之间有着较大的基因表达差异。Nkg7-细胞可进一步被细分为5类NK或NKT细胞亚群，通过对比这些细胞亚群在转移性/非转移性TNBC小鼠肿瘤内的分布差异，研究人员判断NK细胞是其中的主要细胞类型，表明NK细胞很可能是TME中决定肿瘤侵袭性的关键细胞群。锁定“嫌疑”细胞群后，研究人员开始着手分析NK细胞的特性及其在肿瘤微环境中所起的作用。经分析，在侵袭性TNBC小鼠中，其肿瘤NK细胞中负责细胞毒性和NK细胞激活功能的基因表达被下调，并且部分NK细胞亚群的颗粒酶表达也减少，表明这类小鼠TME中的NK细胞对于癌细胞的杀伤能力降低。此外，基因集富集分析结果显示，NK细胞有着更高的炎症反应水平，它们很可能在TNBC肿瘤微环境中发挥着促炎作用。不仅如此，研究人员还发现了未成熟的NK细胞在TNBC肿瘤中数量增加，并且伴有PD-L1及血管生成相关标志物表达升高。在多个侵袭性TNBC肿瘤小鼠TME中，研究人员也观察到了NK细胞的高频率出现，而非TNBC小鼠中则不然。TNBC肿瘤微环境中存在的NK细胞具有明显的表型差异，并且没有完全成熟。和前文的分析一样，它的确与肿瘤转移和血管生成相关。 TME中的NK细胞对于肿瘤细胞的作用恐怕不止于此。研究人员发现，NK细胞中的Wnt配体（如Wnt16）表达上调，并导致癌细胞中Wnt信号通路被激活。当敲除NK细胞的Wnt16基因后，与之共培养的乳腺癌细胞系所形成的肿瘤球（tumorsphere）个数显著减少，表明TNBC肿瘤微环境内的NK细胞通过Wnt信号通路诱导了肿瘤细胞干细胞特性的产生。如果在TME中“清除”这些NK细胞会发生些什么呢？研究人员利用NK1.1抗体耗尽TME中的NK细胞，发现肿瘤的发生和进展都得到了显著改善，同时引发了原发性肿瘤细胞的凋亡增加、癌症转移减少。有趣的是，当NK细胞耗尽后，肿瘤细胞的PD-L1表达降低，研究人员猜测NK细胞或许是参与TNBC肿瘤微环境免疫抑制形成的主要细胞类型。如果是这样，将NK细胞清除和免疫疗法结合或许会有更好的疗效。研究人员没有猜错。他们向TNBC小鼠同时施用NK1.1抗体和PD-L1抗体，以耗尽TME中的NK细胞并降低癌细胞PD-L1的表达，发现与接受PD-L1抗体治疗的小鼠相比，这种组合疗法显著减少了腋窝淋巴结中K14阳性细胞的转移，并且造成原发癌细胞的凋亡增加和血管生成减少。除此外，TME中NK细胞的耗尽改善了TNBC小鼠对奥拉帕利治疗的反应，NK1.1抗体+奥拉帕利的治疗组合同样让癌细胞的凋亡增加，并且具有杀伤能力的CD8+T细胞在TME中的浸润增加，整体上看，小鼠的肿瘤生长被遏制，TME免疫抑制状况也得到了逆转。除了直接“消灭”TME中的NK细胞，阻断癌细胞的Wnt信号通路也被证明可以发挥抗肿瘤功效。当研究人员同时对TNBC小鼠进行Wnt通路抑制剂（LGK-974）和PD-L1抗体处理后，小鼠的肿瘤进展被延缓，并且肿瘤内NK细胞的丰度显著降低，这些指标的表现优于仅接受PD-L1抗体治疗的小鼠。这些数据表明，不论是消耗NK细胞或是抑制Wnt配体分泌，当这些治疗方案与抗PD-L1疗法或化疗联合使用时有望增强对TNBC肿瘤的治疗效力。最后，通过分析人类TNBC样本的基因组和蛋白数据，研究者们发现TNBC患者TME中NK细胞的数量增加，并且NK细胞标志物与TNBC患者的不良临床结局相关，提示上述在小鼠模型中得出的发现与结论在人类中可能同样成立。综上，这项研究揭示了TME中NK细胞除了免疫功能之外，还可以通过激活Wnt信号通路诱导TNBC肿瘤产生干细胞特性，并确定了基于NK细胞、可用于改善TNBC患者预后新的治疗策略。参考资料：[1] Thacker, Gatha et al. “Immature natural killer cells promote progression of triple-negative breast cancer.” Science translational medicine vol. 15,686 (2023): eabl4414. doi:10.1126/scitranslmed.abl4414 内容来源于网络，如有侵权，请联系删除。

免疫疗法细胞疗法临床研究

2022-10-11

·PRNewswire

Esophageal Cancer Clinical Trial Pipeline Insights Featuring 80+ Companies | DelveInsight

The prevalence of esophageal cancer has been rising since the past few years, which prompts the growing demand for the treatment options. The market is driven by the increasing prevalence of cancer and the increase in research & development. The Companies developing the potential therapies in the last stage of development include Celgene,Jiangsu HengRui Medicine Co., Seagen, and several others. LAS VEGAS, Oct. 11, 2022 /PRNewswire/ -- DelveInsight's ' Esophageal Cancer Pipeline Insight – 2022 ' report provides comprehensive global coverage of available, marketed, and pipeline esophageal cancer therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the esophageal cancer pipeline domain. Key Takeaways from the Esophageal Cancer Pipeline Report DelveInsight's esophageal cancer pipeline report depicts a robust space with 80+ active players working to develop 90+ pipeline therapies for esophageal cancer treatment. Leading esophageal cancer companies such as Shanghai Henlius Biotech, CStone Pharmaceuticals, Jiangsu HengRui Medicine Co., Ltd., AstraZeneca, Symphogen, Hoffmann-La Roche, Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Sinocelltech Ltd., Eli Lilly and Company, Ipsen, Jacobio Pharmaceuticals Co., Ltd., Shire, GlaxoSmithKline, Keythera Pharmaceuticals (Australia) Pty Ltd, Sunshine Lake Pharma Co., Ltd., Novartis Pharmaceuticals, Sanofi, Seagen Inc., Rapa Therapeutics LLC, Incyte Corporation, Atreca, Inc., Exelixis, Bayer, BeiGene, Lyell Immunopharma, Sichuan Baili Pharmaceutical, AP Biosciences.,Leap Therapeutics, Inc., Adlai Nortye Biopharma Co., Ltd., Athenex, Inc., Pfizer, Genentech, Hangzhou Neoantigen Therapeutics, Janssen Pharmaceutical, Curis, Inc.,Merck KGaA, Apexigen, Inc,Shenzhen Hornetcorn Bio-technology Company, LTD, MacroGenics, Bristol-Myers Squibb, Integral Molecular, CARTEXELL, EMD Serono, and others are evaluating new drugs for esophageal cancer treatment. Key esophageal cancer pipeline therapies in various stages of development include Serplulimab, CS1001, Camrelizumab, Durvalumab, Sym021, Spartalizumab, Sym022, Sym023, Regorafenib, S095033, INCB099318, RO7121661, XB002, LGK974, Abemaciclib, ladiratuzumab vedotin, ATRC-101, SGN-PDL1V, RO7247669, THOR-707, Letetresgene Autoleucel, TNO155, Anlotinib Hydrochloride, Larotinib, SCT-I10A, KF-0210, SCT200, Ramucirumab, Cabozantinib, JAB-3068, Onivyde, JAB-3312, SGN-B6A, RAPA-201,Ociperlimab, SI B001,Apatinib, AP 203, QEQ278, JAB-3312, DKN-01, AN0025, HR 070803,Oraxol, Sunitinib malate, Tiragolumab, iNeo Vac P01, Amivantamab, CA-4948, M1231, APX005M, DC-CIK, Margetuximab, Temozolomide, and others. In September 2022, Daiichi Sankyo and Sarah Cannon Research Institute (SCRI) announced that extended follow-up data from a phase I/II trial of DS-7300, continued to show promising durable tumor response in patients with several types of heavily pretreated cancers including lung, prostate or esophageal cancer.A response rate of 32% (95% CI: 24-41) was observed with 38 responses (33 confirmed; 28%; 95% CI: 20-37) in 118 patients with various solid tumors including small cell lung cancer (SCLC), squamous non-small cell lung cancer (NSCLC), metastatic castration-resistant prostate cancer (CRPC), esophageal squamous cell carcinoma (ESCC), head and neck squamous cell carcinoma (HNSCC) or endometrial cancer receiving doses of DS-7300 ranging from 4.8 mg/kg to 16.0 mg/kg. In September 2022, Integral Molecular, has licensed a panel of monoclonal antibodies (MAbs) to CARTEXELL, enabling CARTEXELL to develop CAR-T cell therapies using Integral Molecular's Claudin 18.2 (CLDN18.2) MAbs. Under the terms of the agreement, Integral Molecular will provide an exclusive worldwide license to CARTEXELL to use the panel of high-affinity, high-specificity, and fully humanized CLND18.2 MAbs for the development of CAR-T cell therapies against solid tumors including gastric, lung, pancreatic and esophageal cancers. CARTEXELL will be solely responsible for all research, development, and commercial activities. In August 2022, BeiGene announced that the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) has accepted a supplemental biologics license application (sBLA) for tislelizumab in combination with chemotherapy as first-line treatment in patients with unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC). In May 2022, Shanghai Junshi Biosciences Co., Ltd, announced that the China National Medical Products Administration (NMPA) has approved the supplemental new drug application (sNDA) for toripalimab in combination with paclitaxel and cisplatin in the first-line treatment of patients with unresectable locally advanced/recurrent or distant metastatic esophageal squamous cell carcinoma (ESCC). The sNDA was accepted by the NMPA in July 2021. This is the fifth indication approved for toripalimab in China and will benefit Chinese patients with advanced ESCC. In May 2022, Bristol Myers Squibb, announced that the U.S. Food and Drug Administration (FDA) has approved both Opdivo (nivolumab) (injection for intravenous use) in combination with fluoropyrimidine- and platinum-containing chemotherapy and Opdivo plus Yervoy (ipilimumab) as a first-line treatment for adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC) regardless of PD-L1 status. The approvals are based on the Phase III CheckMate -648 trial, which evaluated Opdivo in combination with chemotherapy (n=321) and Opdivo plus Yervoy (n=325) each compared to chemotherapy alone (n=324), and was the largest Phase III trial of immunotherapy in first-line ESCC. In January 2022, Lyell Immunopharma, Inc., announced that the U.S. Food and Drug Administration (FDA) has cleared an Investigational New Drug (IND) application to initiate a Phase I clinical trial for LYL132, an investigational T-cell receptor (TCR) therapy for patients with solid tumors expressing New York esophageal squamous cell carcinoma 1 (NY-ESO-1) that the company is developing in collaboration with GSK. Request a sample and discover the recent advances in esophageal cancer treatment @ Esophageal Cancer Pipeline Report The esophageal cancer pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage esophageal cancer drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the esophageal cancer pipeline landscape. Esophageal Cancer Overview Esophageal cancer grows in the esophagus, the tube that connects the throat to the stomach. Tumors develop in the mucosa, the inner lining of the esophagus. Esophageal cancer is classified into two types, each with its own set of risk factors: Adenocarcinoma -Adenocarcinomas are cancers that begin in gland cells at the bottom of the esophagus. This is the most common type of esophageal cancer. It usually happens near the stomach. The exact esophageal cancer causes are not known. Most esophageal cancer symptoms do not appear until cancer has progressed to an advanced stage, when it may be challenging to treat. Other, more common conditions can cause esophageal cancer symptoms. The most common esophageal cancer symptom is difficulty swallowing, particularly a sensation of food stuck in the chest. There are several tests used for esophageal cancer diagnosis. The most common include endoscopy with biopsy and endoscopic ultrasonography. Find out more about esophageal cancer drugs in development @ New Treatment for Esophageal Cancer A snapshot of the Esophageal Cancer Pipeline Drugs mentioned in the report: Learn more about the emerging esophageal cancer pipeline therapies @ Esophageal Cancer Clinical Trials Esophageal Cancer Therapeutics Assessment The esophageal cancer pipeline report proffers an integral view of esophageal cancer emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Esophageal Cancer Pipeline Report Coverage: Global Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Therapeutics Assessment By Route of Administration: Intra-articular, Intraocular, Intrathecal, Intravenous, Ophthalmic, Oral, Parenteral, Subcutaneous, Topical, Transdermal Therapeutics Assessment By Molecule Type: Oligonucleotide, Peptide, Small molecule Therapeutics Assessment By Mechanism of Action: Prostaglandin E EP4 receptor antagonists, ERBB 2 receptor antagonists, Phosphorylation inhibitors, Antibody-dependent cell cytotoxicity, Apoptosis stimulants, CD40 antigen stimulants, Immunostimulants, Programmed cell death-1 receptor antagonists, T lymphocyte stimulants, Programmed cell death-1 ligand-1 inhibitors, Epidermal growth factor receptor antagonists. Key Esophageal Cancer Companies: Shanghai Henlius Biotech, CStone Pharmaceuticals, Jiangsu HengRui Medicine Co., Ltd., AstraZeneca, Symphogen, Hoffmann-La Roche, Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Sinocelltech Ltd., Eli Lilly and Company, Ipsen, Jacobio Pharmaceuticals Co., Ltd., Shire, GlaxoSmithKline, Keythera Pharmaceuticals (Australia) Pty Ltd, Sunshine Lake Pharma Co., Ltd., Novartis Pharmaceuticals, Sanofi, Seagen Inc., Rapa Therapeutics LLC, Incyte Corporation, Atreca, Inc., Exelixis, Bayer, BeiGene, Lyell Immunopharma, Sichuan Baili Pharmaceutical, AP Biosciences.,Leap Therapeutics, Inc., Adlai Nortye Biopharma Co., Ltd., Athenex, Inc., Pfizer, Genentech, Hangzhou Neoantigen Therapeutics, Janssen Pharmaceutical, Curis, Inc.,Merck KGaA, Apexigen, Inc,Shenzhen Hornetcorn Bio-technology Company, LTD, MacroGenics, Bristol-Myers Squibb, Integral Molecular, CARTEXELL and others Key Esophageal Cancer Pipeline Therapies: Serplulimab, CS1001, Camrelizumab, Durvalumab, Sym021, Spartalizumab, Sym022, Sym023, Regorafenib, S095033, INCB099318, RO7121661, XB002, LGK974, Abemaciclib, ladiratuzumab vedotin, ATRC-101, SGN-PDL1V, RO7247669, THOR-707, Letetresgene Autoleucel, TNO155, Anlotinib Hydrochloride, Larotinib, SCT-I10A, KF-0210, SCT200, Ramucirumab, Cabozantinib, JAB-3068, Onivyde, JAB-3312, SGN-B6A, RAPA-201,Ociperlimab, SI B001,Apatinib, AP 203, QEQ278, JAB-3312, DKN-01, AN0025, HR 070803,Oraxol, Sunitinib malate, Tiragolumab, iNeo Vac P01, Amivantamab, CA-4948, M1231, APX005M, DC-CIK, Margetuximab, Temozolomide and others. Dive deep into rich insights for esophageal cancer drugs, visit @ Chemo Drugs for Esophageal Cancer Treatment Table of Contents For further information on the esophageal cancer pipeline therapeutics, reach out @ New Drug for Esophageal Cancer Treatment Related Reports Esophageal Cancer Market Esophageal Cancer Market Insights, Epidemiology, and Market Forecast – 2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key esophageal cancer companies including Merck KGaA, Shenzhen Hornetcorn Biotechnology, Apexigen, Inc., Highlight Therapeutics, among others. Esophageal Cancer Epidemiology Forecast Esophageal Cancer Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted esophageal cancer epidemiology in the 7MM, i.e., the United States, EU5 (Germany, Spain, Italy, France, and the United Kingdom), and Japan. Esophageal Squamous Cell Carcinoma Pipeline Esophageal Squamous Cell Carcinoma Pipeline Insight – 2022 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key esophageal squamous cell carcinoma companies, including BeiGene, AstraZeneca, Ipsen, Shire, Sanofi, Seagen, among others. Esophageal Squamous Carcinoma Market Esophageal Squamous Carcinoma Market Insights, Epidemiology, and Market Forecast – 2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key esophageal squamous carcinoma companies, including BeiGene, AstraZeneca, Ipsen, Shire, Sanofi, Seagen, among others. Esophageal Squamous Cell Carcinoma Epidemiology Esophageal Squamous Cell Carcinoma Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted esophageal squamous cell carcinoma epidemiology in the 7MM, i.e., the United States, EU5 (Germany, Spain, Italy, France, and the United Kingdom), and Japan. 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Connect with us at LinkedIn Contact Us Shruti Thakur [email protected] +1(919)321-6187 Logo: SOURCE DelveInsight Business Research, LLP

基因疗法抗体生物类似药寡核苷酸细胞疗法

100 项与 LGK-974 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12561

研发状态

适应症	最高研发状态	国家/地区	公司
结直肠癌	临床2期	-	Novartis Pharma AG 更多
食管鳞状细胞癌	无进展	荷兰更多	Novartis Pharma AG 更多
三阴性乳腺癌	无进展	西班牙更多	Novartis Pharma AG 更多
黑色素瘤	无进展	西班牙更多	Novartis Pharma AG 更多
胰腺癌	无进展	美国更多	Novartis Pharma AG 更多

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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


NCT01351103 (AACR2020) 人工标引	临床1期	HR阳性/HER2低表达实体瘤	27	LGK-974+spartalizumab	(選範鹹顧餘夢鹽簾簾餘) = NE 淵願鏇獵衊蓋鏇壓衊願 (壓鹽鬱衊鹹糧獵鹹鬱範 ) 更多	积极	2020-04-27
NCT01351103 (Pubmed \| Med J Aust) 人工标引	临床1期	肿瘤	94	WNT974	(壓齋淵網遞願選齋製觸) = Dysgeusia（50%）鹽餘範膚積簾選獵齋蓋 (繭淵繭網繭憲鹹築獵觸 ) 更多	积极	2021-07-01
AACR2018	N/A	卵巢癌	-	WNT974	(蓋醖淵膚衊構獵顧願觸) = 艱遞鑰醖範憲觸獵艱範鑰糧鑰簾鏇淵窪顧憲鹽 (積選網簾壓夢鏇窪鹹繭 ) 更多	-	2018-07-01
AACR2018	N/A	卵巢癌	-	ddPac	(蓋醖淵膚衊構獵顧願觸) = 顧壓壓壓範窪製鹽製憲鑰糧鑰簾鏇淵窪顧憲鹽 (積選網簾壓夢鏇窪鹹繭 ) 更多	-	2018-07-01