A Phase 1/2, Randomized Study Evaluating Multiple Nivolumab Combination Therapies in Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer (NSCLC) After Failure of Platinum-Based Chemotherapy and Anti-PD-1 (L)1 Immunotherapy

This study is for participants with Non-small Cell Lung Cancer that has spread or has reoccurred after failure of Chemotherapy and Immunotherapy

开始日期2021-04-15

申办/合作机构

Bristol Myers Squibb Co.

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100 项与德立替尼相关的临床结果

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100 项与德立替尼相关的转化医学

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100 项与德立替尼相关的专利（医药）

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项与德立替尼相关的文献（医药）

2022-10-01·Journal of Immunotherapy

The Multi-Kinase Inhibitor Lucitanib Enhances the Antitumor Activity of Coinhibitory and Costimulatory Immune Pathway Modulators in Syngeneic Models

Article

作者: Liao, Mingxiang ; Simmons, Andrew D. ; Nguyen, Minh ; Dusek, Rachel L. ; Harding, Thomas C. ; Robillard, Liliane

Lucitanib is a multi-tyrosine kinase inhibitor whose targets are associated with angiogenesis and other key cancer and immune pathways. Its antiangiogenic properties are understood, but lucitanib’s immunomodulatory activity is heretofore unknown. Lucitanib exhibited such activity in vivo, increasing CD3+, CD8+, and CD4+ T cells and decreasing dendritic cells and monocyte-derived suppressor cells in mouse spleens. Depletion of CD8+ T cells from syngeneic MC38 colon tumor-bearing mice reduced the antitumor efficacy of lucitanib and revealed a CD8+ T-cell-dependent component of lucitanib’s activity. The combination of lucitanib and costimulatory immune pathway agonists targeting 4-1BB, glucocorticoid-induced TNFR (GITR), inducible T-cell co-stimulator (ICOS), or OX40 exhibited enhanced antitumor activity compared with each single agent in immunocompetent tumor models. Lucitanib combined with blockade of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) or programmed cell death protein-1 (PD-1) coinhibitory immune pathways also showed enhanced antitumor activity over the single agents in multiple models. In CT26 tumors, lucitanib, alone or combined with anti-PD-1, reduced CD31+ vessels and depleted F4/80+ macrophages. Combination treatment also increased the number of intratumoral T cells. Gene expression in pathways associated with immune activity was upregulated by lucitanib in MC38 tumors and further potentiated by combination with anti-PD-1. Accordingly, lucitanib, alone or combined with anti-PD-1, increased intratumoral CD8+ T-cell abundance. Lucitanib’s antitumor and pharmacodynamic activity, alone or combined with anti-PD-1, was not recapitulated by specific vascular endothelial growth factor receptor-2 (VEGFR2) inhibition. These data indicate that lucitanib can modulate vascular and immune components of the tumor microenvironment and cooperate with immunotherapy to enhance antitumor efficacy. They support the clinical development of lucitanib combined with immune pathway modulators to treat cancer.

2022-09-01·Surgical Oncology

Gene signature and connectivity mapping to assist with drug prediction for pancreatic ductal adenocarcinoma

Article

作者: Cloyd, Jordan M ; Pawlik, Timothy M ; Xu, Gang ; Mao, Yilei ; Du, Shunda ; Zhang, Baoluhe ; Xiao, Yao

INTRODUCTIONThe prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) is highly variable and there is a paucity of effective treatment options for patients with PDAC. Genome-wide analyses may allow for potential drugs to be identified using differentially expressed genes, as well as constructing protein interaction networks and molecule-gene connectivity mapping.METHODSMicroarray data of RNA expression profiling of PDAC and normal pancreas tissues were downloaded from the Gene Expression Omnibus (GEO). Functional and pathway enrichment information of the DEGs was obtained using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. Corresponding homologous proteins were analyzed by protein-protein interaction analysis. Survival-related hub genes were screened and potential therapeutic drugs for PDAC were identified using the connectivity mapping (cMap).RESULTSOf 18,229 PDAC genes assessed using RNA expression profiling from 118 PDAC tumor samples and 13 normal pancreatic tissue samples, 1502 and 744 genes were upregulated and downregulated, respectively, versus normal pancreas tissue. Protein-protein interaction analysis revealed 10 upregulated hub genes (ITGB1, ITGAV, SDC1, KRAS, CCNB2, COL1A2, AURKA, CDC20, COL1A1, COL3A1) and 10 downregulated hub genes (CPB1, CPA1, CPA2, CTRB2, CTRC, CELA3A, CELA2B, PRSS3, CELA2A, REG1A). The connectivity mapping score related to this hub gene list was used to generate the candidate drugs for PDAC treatment, which includes tyrosine kinase inhibitors (lucitanib, lapatinib, ceritinib and CYT-387), serine/threonine protein kinase inhibitors (roscovitine, BS-181, purvalanol-a, MK-2206 and palomid-529) and other small molecules.CONCLUSIONUsing available genetic atlas data, potential drug candidates for treatment of PDAC were identified based on differentially expressed genes, protein interaction analysis and connectivity mapping. These results may help focus efforts on identifying targeted agents with potential therapeutic efficacy for evaluation in prospective clinical trials of patients with PDAC.

2022-09-01·European Journal of Drug Metabolism and Pharmacokinetics

Population Pharmacokinetic Modeling of Lucitanib in Patients with Advanced Cancer

Article

作者: Wride, Kenton ; Lepley, Denise ; Liao, Mingxiang ; Cameron, Terri ; Zhou, Jie ; Sale, Mark ; Xiao, Jim

BACKGROUNDLucitanib is an oral, potent, selective inhibitor of the tyrosine kinase activity of vascular endothelial growth factor receptors 1‒3, fibroblast growth factor receptors 1‒3, and platelet-derived growth factor receptors alpha/beta.OBJECTIVEWe aimed to develop a population pharmacokinetics (PopPK) model for lucitanib in patients with advanced cancers.METHODSPopPK analyses were based on intensive and sparse oral pharmacokinetic data from 5 phase 1/2 clinical studies of lucitanib in a total of 403 patients with advanced cancers. Lucitanib was administered at 5‒30 mg daily doses as 1 of 2 immediate-release oral formulations: a film-coated tablet or a hard gelatin capsule.RESULTSLucitanib pharmacokinetics were best described by a 2-compartment model with zero-order release into the dosing compartment, followed by first-order absorption and first-order elimination. Large between-subject pharmacokinetic variability was partially explained by body weight. No effects of demographics or tumor type on lucitanib pharmacokinetics were observed. The model suggested that the formulation impacted release duration (tablet, 0.243 h; capsule, 0.814 h), but the effect was not considered clinically meaningful. No statistically significant effects were detected for concomitant cytochrome P450 (CYP) 3A4 inhibitors or inducers, CYP2C8 or P-glycoprotein inhibitors, serum albumin, mild/moderate renal impairment, or mild hepatic impairment. Concomitant proton pump inhibitors had no clinically significant effect on lucitanib absorption.CONCLUSIONSThe PopPK model adequately described lucitanib pharmacokinetics. High between-subject pharmacokinetic variability supports a safety-based dose-titration strategy currently being used in an ongoing clinical study of lucitanib to optimize drug exposure and clinical benefit.TRIAL REGISTRATIONClinicalTrials.gov Identifier: NCT01283945, NCT02053636, ISRCTN23201971, NCT02202746, NCT02109016.

项与德立替尼相关的新闻（医药）

2024-10-25

·ioncology

ESMO ASIA 2024丨一文了解胸部肿瘤口头报告

点击蓝字关注我们 2024年欧洲肿瘤内科学会亚洲年会（ESMO Asia Congress 2024）将于当地时间12月6日~8日在新加坡召开。ESMO ASIA是亚太地区讨论肿瘤学领域重磅突破的领先平台，近日在官方网站正式公布本次大会的摘要题目及作者信息。肿瘤瞭望小编带您先睹为快，一览胸部肿瘤领域入选优选口头报告（Proffered Paper）和微型口头报告（Mini Oral）的临床研究。 1 优选口头报告（Proffered Paper）摘要号：LBA8 英文标题：Phase II trial of atezolizumab plus carboplatin and paclitaxel in patients with metastatic or recurrent thymic carcinoma: Marble study 中文标题：阿替利珠单抗+卡铂/紫杉醇治疗转移性或复发性胸腺癌的II期临床试验：Marble研究讲者：Tomoyasu Mimori (日本) 摘要号：625O 英文标题：Efficacy and safety of Lucitanib (AL3810) in second or subsequent-line treatment of advanced recurrent or metastatic thymic carcinoma: a randomized, double-blind, placebo-controlled multicenter phase II trial 中文标题：Lucitanib在晚期复发或转移性胸腺癌二线或后续治疗中的疗效和安全性：一项随机、双盲、安慰剂对照的多中心II期试验讲者：方文涛（上海交通大学医学院附属胸科医院）摘要号：LBA5 英文标题：Zongertinib in patients with HER2-mutant NSCLC: Updated analysis of Beamion LUNG-1 中文标题：Zongertinib治疗HER2突变型NSCLC患者：Beamion LUNG-1的最新分析讲者：Noboru Yamamoto (日本) 摘要号：LBA6 英文标题：PACIFIC-5: A phase 3 study of consolidation durvalumab (D) in patients (pts) with unresectable stage III NSCLC and no progression after concurrent or sequential chemoradiotherapy (cCRT or sCRT) 中文标题：PACIFIC-5：针对同步或序贯放化疗（cCRT或sCRT）后未出现进展不可切除III期NSCLC患者进行巩固性度伐利尤单抗治疗的III期研究讲者：吴一龙（广东省人民医院）摘要号：LBA7 英文标题：Efficacy and safety of datopotamab deruxtecan (Dato-DXd) in patients (pts) with previously-treated EGFR-mutated advanced non-small cell lung cancer (NSCLC): a pooled analysis of TROPION-Lung01 and TROPION-Lung05 中文标题：Dato-DXd对既往接受过治疗的EGFR突变晚期非小细胞肺癌患者的疗效和安全性：TROPION-Lung01和TROPION-Lung05的汇总分析讲者：Myung-Ju Ahn (韩国) 2 微型口头报告（Mini Oral）摘要号：626MO 英文标题：Tarlatamab in previously treated small cell lung cancer (SCLC): Subgroup analysis of patients from the Asia region in the phase 2 DeLLphi-301 study 中文标题：Tarlatamab治疗既往接受过治疗的小细胞肺癌：II期DeLLphi-301研究中亚洲地区患者的亚组分析讲者：Hiroaki Akamatsu (日本) 摘要号：627MO 英文标题：POD1UM-304: Phase 3 Study of Retifanlimab Plus Platinum-Based Chemotherapy (Chemo) as First-Line (1L) Therapy For Nonsquamous or Squamous Metastatic Non–Small Cell Lung Cancer (mNSCLC) 中文标题：POD1UM-304：Retifanlimab+铂类化疗作为非鳞或鳞状转移性非小细胞肺癌一线疗法的III期研究讲者：陆舜(上海交通大学医学院附属胸科医院) 摘要号：614MO 英文标题：A Phase Ⅱ Study of Becotatug (JMT101) in Combination with Osimertinib (Osi) in Patients (pts) with classical EGFR-mutated Non-small Cell Lung Cancer (NSCLC) (BOOSTER Study) 中文标题：Becotatug联合奥希替尼治疗经典型EGFR突变非小细胞肺癌患者的Ⅱ期BOOSTER临床研究讲者：张力(中山大学肿瘤防治中心) 摘要号：630MO 英文标题：First-line (1L) osimertinib (osi) ± platinum-pemetrexed chemotherapy (CTx) for EGFR-mutated (EGFRm) advanced non-small cell lung cancer (NSCLC): FLAURA2 Asian cohort 中文标题：一线奥希替尼±铂类-培美曲塞化疗治疗EGFR突变晚期非小细胞肺癌：FLAURA2亚洲队列讲者：James Chih-Hsin Yang (中国台湾) 摘要号：628MO 英文标题：Comparing Subcutaneous vs Intravenous Amivantamab with Lazertinib in EGFR-Mutated Advanced NSCLC: Analysis of Asian Patients From PALOMA-3 中文标题：比较皮下注射vs静脉注射Amivantamab联合Lazertinib治疗EGFR突变晚期NSCLC：对PALOMA-3亚洲患者的分析讲者：Se-Hoon Lee (韩国) 摘要号：629MO 英文标题：ALESIA 7-year update: alectinib vs crizotinib in Asian patients (pts) with treatment-naïve advanced ALK+ non-small cell lung cancer (NSCLC) 中文标题：ALESIA研究7年随访更新：阿来替尼vs克唑替尼在未经治疗的晚期ALK+非小细胞肺癌亚洲患者中的疗效对比讲者：周彩存(上海市东方医院) （来源：《肿瘤瞭望》编辑部）声明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

临床2期临床结果临床3期

2024-10-03

·药渡

浅谈：FGFR靶向治疗的临床进展

前言成纤维细胞生长因子（FGF）通过FGF受体（FGFR1-4）发出信号，协调胎儿发育，有助于组织和全身稳态，但FGFR基因的融合、重排或突变也可能促进肿瘤发生。FGFR融合可分为I型（非受体型，由融合伴侣的N端置换引起，如BCR-FGFR1和ZYM2-FGFR1）、IIa型（受体型，也由融合伴侣N端置换产生；如FN1-FGFR1、KLK2-FGFR2）或IIb型（受体型，由融合伴侣C端置换产生；如FGFR2-BICC1、FGFR3-TACC3）。在实体瘤中检测到的FGFR变化包括非小细胞肺癌中的FGFR1扩增（20%）、乳腺癌中的FGFR 1/2扩增（7-23%）、尿路上皮癌中的FGFR3突变（10-60%）或FGFR3融合（6%）、肝内胆管癌中的FGFR2融合（10-20%）、子宫内膜癌中的FGFR2突变（12%）和胃癌中FGFR2的扩增（5-10%）。在约7.0%的未经选择的癌症患者中可以检测到FGFR基因的改变。目前，已经开发出了多种FGFR靶向药物，包括泛FGFR抑制剂（erdafitinib和futibatinib）、FGFR1/2/3抑制剂（infigratinib和pemigatinib），以及一系列更具特异性的药物，其中一些已进入临床使用。Erdafitinib已被批准用于携带FGFR2/3突变的尿路上皮癌患者，futibatinib和pemigatinib被批准治疗携带FGFR2融合或重排的胆管癌患者。这些药物的临床益处在一定程度上受到高磷血症的限制，这是由于FGFR1的脱靶抑制以及FGFR基因中耐药性突变的出现。下一代小分子抑制剂，如lirafugratinib和LOXO-435，以及FGFR2特异性抗体bemarituzumab，有望降低高磷血症的风险，并有能力克服某些耐药性突变。 FGFR的结构和信号通路 FGFs由具有球状或非典型β三叶结构的保守核心结构域组成，可分为典型FGFs（FGF1-10、FGF16-18、FGF20和FGF22）、内分泌型FGF（FGF19/FGF15、FGF21和FGF23）以及FGF同源因子（FGF11-14）。全长FGF受体（FGFR1-4）是I型跨膜蛋白，具有三个细胞外免疫球蛋白样结构域和一个胞内酪氨酸激酶结构域。典型的FGF与硫酸乙酰肝素辅因子一起通过FGFR传递信号，而内分泌型FGF与klotho共受体（KLA和KLB）和硫酸乙酰肝素辅助因子一起通过FGFR传递信号。FGF–FGFR信号传导参与细胞存活、增殖、代谢、迁移和分化，包括生理作用，如协调胎儿发育和维持组织和/或全身稳态。这些受体也可以驱动肿瘤的发展。 FGFR中配体依赖性二聚化或病理改变通过自身抑制机制释放而导致内源性激酶激活。FGFR激活导致FRS2依赖性激活PI3K–AKT、RAS–ERK和磷脂酶Cγ（PLCγ）依赖性二酰基甘油（DAG）–PKC和IP3–Ca2+信号。癌症患者的FGFR改变通过异常的FGFR信号传导促进肿瘤发生：FGFR扩增导致FGFR过度表达和下游信号通路过度激活；FGFR融合或重排导致融合伴侣介导的FGFR二聚化、磷酸化改变和异常的下游信号传导；细胞外区或跨膜结构域中的FGFR突变通过改变对FGF配体的特异性或亲和力，以及配体非依赖性二聚化来激活FGFR；酪氨酸激酶结构域中的FGFR突变由于自身抑制机制的破坏而结构性性地激活FGFR。小分子FGFR抑制剂几种小分子FGFR抑制剂已被开发用于治疗具有FGFR改变的癌症患者，如尿路上皮癌、乳腺癌、胃癌、肝癌、肺癌、卵巢癌和宫颈癌。能够与酪氨酸激酶结构域的ATP结合位点结合的FGFR抑制剂通常分为多激酶FGFR抑制剂或选择性FGFR抑制剂。Derazatinib、dovitinib、tasurgratinib、lenvatinib、lucitanib、nintedanib和ponatinib都是多激酶FGFR抑制剂，对FGFR以外的多种RTK具有活性。然而，由于其广泛的活性，与选择性FGFR抑制剂相比，多激酶FGFR抑制剂的作用机制和不良反应都很复杂。选择性FGFR抑制剂包括泛FGFR、FGFR1/2/3和FGFR2/3抑制剂以及选择性FGFR2、FGFR3或FGFR4抑制剂。泛FGFR抑制剂包括 erdafitinib, futibatinib, rogaratinib和resigratinib；FGFR1/2/3抑制剂包括pemigatinib, infigratinib, fexagratinib和zoligratinib；Lirafugratinib是一种选择性FGFR2抑制剂，LOXO-435是一种选择FGFR3抑制剂，roblitinib和fissotioninib是选择性FGFR4抑制剂。目前，根据在II期试验中观察到的疗效和耐受性，美国食品药品监督管理局（FDA）在这些适应症的二线或更后线的治疗中加速批准erdafitinib、futibatinib、infigratinib和pemiginib。在erdafitinib的临床研究（BLC2001）中，根据FGFR3或FGFR2/FGFR3融合物中至少一种突变的存在，选择局部晚期和/或不可切除的尿路上皮癌患者。整体队列的ORR为40%，中位无进展生存期（mPFS）和中位总生存期（mOS）分别为5.5个月和13.8个月。46%的患者出现≥3级不良事件，在初步分析中包括低钠血症（11%）、口腔炎（10%）和乏力（7%），以及长期随访的指甲（15%）、口炎（14%）和皮肤事件（8%）。在FIGHT-203的II期研究中，在携带I型FGFR1融合（如ZMYM2–FGFR1或BCR–FGFR2）的MLN患者中测试了pemiginib的药效和安全性。其中77%（24/31）的患者对pemiginib有完全响应。常见的≥3级不良事件包括贫血（18%）、口腔炎和四肢疼痛（均为12%）。2022年8月，FDA批准了pemiginib用于携带FGFR1融合的复发性和/或难治性MLN患者。任何级别的高磷血症都发生在大多数接受泛FGFR抑制剂或FGFR1/2/3抑制剂的患者中。这种不良反应很可能反映了泛FGFR或FGFR1/2/3抑制剂对FGF23信号传导的抑制，因为这种分泌蛋白依赖于与近端小管上皮细胞膜上的FGFR1和klotho的结合。该复合物通过抑制磷酸钠协同转运蛋白（NPT2a/c）调节肾脏中的磷酸盐吸收。FGFR1在这一过程中的作用得到证实，因此，开发FGFR2特异性和FGFR3特异性抑制剂有望避免或降低这种不良反应的发生率。 FGFR抑制性单克隆抗体在靶向FGF/FGFR信号的生物制剂中，bemarituzumab是目前正在III期试验中评估的唯一药物。bemarituzumab是一种人源化抗FGFR2b抗体，其抑制FGF7、FGF10和FGF22的结合，从而抑制癌细胞中配体诱导的FGFR2b信号传导，并且由于修饰的Fc结构域对自然杀伤细胞上的人FcγRIIIA受体的亲和力增加，因此具有诱导抗体依赖性细胞介导的细胞毒性（ADCC）的能力。在一项涉及晚期FGFR2b过表达胃和胃食管交界腺癌（GEA）患者的I期试验中，bemarituzumab单药治疗显示出可接受的耐受性，ORR为18%（5/28）。随后，在携带FGFR2扩增或FGFR2过表达的GEA患者的II期FIGHT试验中，将bemarituzumab与mFOLFOX6（包括氟嘧啶、亚叶酸和奥沙利铂）联合测试。bemarituzumab联合化疗组和安慰剂联合化疗组患者的ORR分别为53%和40%，mPFS分别为9.5个月和7.4个月（P=0.073)。bemarituzumab的其他几项试验，包括评估bemarituzumab联合mFOLFOX6加(NCT0511626) 或不加(NCT050252801) nivolumab在先前未经治疗的晚期GEA患者中的研究正在进行中。新型FGFR靶向疗法蛋白水解靶向嵌合体（PROTAC）、嵌合抗原受体（CAR）T细胞、抗体偶联药物（ADC）、放射免疫偶联物（RICs）和可溶性受体是能够靶向FGF–FGFR信号级联的潜在新治疗模式，其中一些已经或正在临床试验中进行测试。 PROTAC PROTAC具有双重部分，使其能够与靶蛋白和E3泛素连接酶相互作用，从而诱导靶蛋白的泛素化介导的蛋白酶体降解。LC-MB12是一种基于infigratinib的PROTAC，能够优先降解FGFR2，并抑制表达TEL–FGFR2融合的Ba/F3细胞和FGFR2扩增的SNU16癌细胞的增殖。相比之下，DGY-09-192是另一种基于 infigratinib的PROTAC，旨在募集von Hippel–Lindau蛋白（VHL），从而优先降解FGFR1和FGFR2。这些药物目前仍处于临床前开发阶段。 CAR-T细胞由于PAX3–FOXO1的下游作用，FGFR4在儿科横纹肌肉瘤中普遍过表达。然而，N535K和V550L等耐药性突变通常在治疗前出现，这可能会限制小分子抑制剂的有效性。因此，研究人员开发了靶向FGFR4的CAR-T细胞，如RJ154-HL和3A11，具有不同的靶向FGFR4的scFv。目前，靶向FGFR的CAR-T细胞也仍处于临床前开发阶段。基于抗体的药物 Aprutumab是一种全人源抗FGFR2抗体，它识别FGFR2b和FGFR2c亚型共同N末端区域P23、L27和E29周围的表位，并已被证明能诱导这些变体的内化和运输至溶酶体降解。Aprutumab和bemarituzumab在I期临床试验中均显示出良好的安全性和耐受性。目前，bemarituzumab已作为联合疗法进行II期和III期临床试验，而Aprutumab用于开发ADCs和RICs。 Aprutumab ixadotin（前身为BAY-1187982）是具有不可裂解连接子的抗FGFR2 ADC，LY3076226是具有可裂解连接子的抗FGFR3 ADC。然而，测试这两种药物的第一阶段试验(nct22368951)由于耐受性差和活性有限而终止。此外，Aprutumab和抗FGFR3抗体vofatamab分别用于FGFR2靶向的RIC（227Th-Aprutumab，BAY 2304058）和FGFR3靶向的RIC，225Ac-vofatamab（FPI-1966）和111In vofatamab（FPI-1967）。BAY 2304058仍处于临床前开发阶段，而FPI-1966（用于放射免疫疗法）和FPI-1967（用于放射成像）目前正在I/II期试验(NCT05363605)中进行测试，用于表达FGFR3的晚期实体瘤患者。可溶性FGFR受体可溶性FGFR受体，如衍生自FGFR1c的细胞外结构域的FP-1039和衍生自FGFR 3c的细胞外区域的Recifecept，是另一类通过充当诱饵受体来捕获FGFR配体的重组蛋白药物。FP-1039已显示对促有丝分裂FGF配体具有高亲和力，并且在FGFR1扩增的肺癌和FGFR2突变的子宫内膜癌的小鼠异种移植模型中具有抗肿瘤作用。FP-1039在一期试验中具有可接受的耐受性。测试FP-1039与各种化疗联合用药的Ib期试验(NCT01868022) 显示同时接受紫杉醇和卡铂治疗的鳞状非小细胞肺癌患者的ORR为47%，同时接受培美曲塞和顺铂治疗的恶性胸膜间皮瘤患者的ORR为39%。小结目前，小分子FGFR抑制剂和FGFR靶向抗体药物已在临床后期试验中进行开发和测试，其中几种小分子FGFR抑制剂已被批准用于FGFR改变的癌症患者。尽管如此，某些不良事件，如FGFR1脱靶抑制引起的高磷血症和获得性耐药性，仍然限制了这些药物的临床益处。选择性第三代抑制剂，如特异性靶向FGFR2或FGFR3的抑制剂，正在临床开发中，这些药物可能避免或显著降低高磷血症的风险，并可能克服突变介导的耐药性。参考文献： 1.FGFR-targeted therapeutics: clinical activity, mechanisms of resistance and new directions. Nat Rev Clin Oncol.2024 Feb 29 药渡媒体商务合作媒体公关 | 新闻&会议发稿张经理：18600036371（微信同号）点击下方“药渡“，关注更多精彩内容免责声明 “药渡”公众号所转载该篇文章来源于其他公众号平台，主要目的在于分享行业相关知识，传递当前最新资讯。图片、文章版权均属于原作者所有，如有侵权，请及时告知，我们会在24小时内删除相关信息。微信公众号的推送规则又双叒叕改啦，如果您不点个“在看”或者没设为"星标"，我们可能就消散在茫茫文海之中~点这里，千万不要错过药渡的最新消息哦！👇👇👇

引进/卖出临床结果

2024-09-19

·PRNewswire

Mantle Cell Lymphoma Clinical Trial Pipeline Insights Featuring 20+ Companies | DelveInsight

Mantle cell lymphoma is a rare and aggressive type of non-Hodgkin lymphoma originating from B-cells in the "mantle zone" of the lymph nodes. The development of novel targeted therapies and immunotherapies, such as Bruton's tyrosine kinase (BTK) inhibitors, is improving treatment outcomes and driving market growth for Mantle cell lymphoma. LAS VEGAS, Sept. 19, 2024 /PRNewswire/ -- DelveInsight's ' Mantle Cell Lymphoma Pipeline Insight 2024 ' report provides comprehensive global coverage of pipeline mantle cell lymphoma therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the mantle cell lymphoma pipeline domain. Key Takeaways from the Mantle Cell Lymphoma Pipeline Report DelveInsight's mantle cell lymphoma pipeline report depicts a robust space with 20+ active players working to develop 22+ pipeline therapies for mantle cell lymphoma treatment. Key mantle cell lymphoma companies such as AbbVie, Adicet Bio, InnoCare Pharma Inc., Guangzhou Lupeng Pharmaceutical Company LTD., BeiGene, Nurix, LegoChem Biosciences, Xynomic Pharmaceuticals, Merck & Co, Incyte Corporation, TG Therapeutics, Janssen/Pharmacyclics, Eternity Bioscience, Traws Pharm, Advenchen Laboratories, and others are evaluating new mantle cell lymphoma drugs to improve the treatment landscape. Promising mantle cell lymphoma pipeline therapies such as Venetoclax, ADI-001, Orelabrutinib, LP-168, BGB-11417, NX 2127, LCB 71, NX 5948, Abexinostat, Pembrolizumab, Parsaclisib, Umbralisib, Ibrutinib, Edralbrutinib, Narazaciclib, Lucitanib, and others are under different phases of mantle cell lymphoma clinical trials. In May 2024, AstraZeneca had announced positive interim results from the Phase III ECHO clinical trial, which evaluated Bruton's tyrosine kinase (BTK) inhibitor Calquence (acalabrutinib) in combination with standard chemoimmunotherapy for treating mantle cell lymphoma (MCL). In March 2024, BeiGene, Ltd. announced the presentation of emerging oncology pipeline data at the American Association for Cancer Research (AACR) Annual Meeting. Additional highlights include preclinical characterization data for an investigational BTK degrader, BGB-16673, currently in clinical development for B-cell malignancies, including mantle cell lymphoma In October 2023, Ascentage Pharma announced that it has entered into a clinical collaboration with AstraZeneca Investment. The two companies will jointly conduct a registrational Phase III study of the Bcl-2 inhibitor, APG-2575 (lisaftoclax), in combination with AstraZeneca's Bruton's tyrosine kinase (BTK) inhibitor, CALQUENCE® (acalabrutinib), in treatment-naive patients with first-line chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). In January 2023, the FDA granted an orphan drug designation to LP-284, a novel small-molecule, next-generation acylfulvene, for the treatment of mantle cell lymphoma (MCL), a rare and aggressive form of B-cell non-Hodgkin lymphoma (NHL), according to an announcement from Lantern Pharma. Request a sample and discover the recent advances in mantle cell lymphoma treatment drugs @ Mantle Cell Lymphoma Pipeline Report The mantle cell lymphoma pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage mantle cell lymphoma drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the mantle cell lymphoma clinical trial landscape. Mantle Cell Lymphoma Overview Mantle cell lymphoma (MCL) is a rare subtype of B-cell non-Hodgkin lymphomas (NHLs) characterized by the (11,14) translocation, leading to overexpression of the cyclin D1 (CCND1) gene. Its various morphological variants can make diagnosis challenging, though some cases are straightforward. Many individuals with MCL are asymptomatic in the early stages, but may later seek medical attention due to persistent, typically painless swelling of lymph nodes, especially in the neck and throat region (e.g., Waldeyer's ring). MCL is marked by a reciprocal chromosomal translocation t(11;14)(q13;q32), which places the cyclin D1 gene next to the immunoglobulin heavy chain gene, causing continuous cyclin D1 expression. This overexpression contributes to tumor cell proliferation through cell cycle dysregulation, chromosomal instability, and epigenetic changes. Rarely, MCL cases without this translocation may involve CCND2 or CCND3 translocations. Hypothetical molecular subtypes, based on the cell of origin, correlate with clinical phenotypes: classical or aggressive MCL arises from naive B cells lacking or having limited iGVH mutations and expressing SOX11, a neural transcription factor inhibiting terminal B cell differentiation. The indolent variant originates from antigen-experienced B cells with IGVH somatic hypermutations, typically SOX11-negative and genetically stable. Diagnosis of MCL involves detailed patient history, thorough clinical evaluation, and specialized tests, including biopsy of an affected lymph node or bone marrow. These tests confirm the NHL type and subtype, assess disease extent, and determine appropriate treatments. Treatment for MCL is multifaceted and tailored to each patient, often including chemotherapy, immunotherapy drugs like rituximab, targeted therapies such as ibrutinib, and stem cell transplants, particularly for aggressive disease or younger patients. Radiation therapy may target specific lymphoma areas. Participation in clinical trials can offer new treatment options. Treatment plans are developed collaboratively by healthcare professionals and patients, considering disease stage, overall health, and personal preferences. Regular monitoring and follow-up care are essential to track treatment response and manage side effects effectively. Find out more about mantle cell lymphoma treatment drugs @ Drugs for Mantle Cell Lymphoma Treatment A snapshot of the Mantle Cell Lymphoma Pipeline Drugs mentioned in the report: Learn more about the emerging mantle cell lymphoma pipeline therapies @ Mantle Cell Lymphoma Clinical Trials Mantle Cell Lymphoma Therapeutics Assessment The mantle cell lymphoma pipeline report proffers an integral view of the mantle cell lymphoma emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Mantle Cell Lymphoma 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: Oral, Parenteral, Intravenous, Subcutaneous, Topical Therapeutics Assessment By Molecule Type: Recombinant fusion proteins, Small molecule, Monoclonal antibody, Peptide, Polymer, Gene therapy Therapeutics Assessment By Mechanism of Action: Apoptosis stimulants, Proto-oncogene protein c-bcl-2 inhibitors, Proteasome inhibitors, Immunologic cytotoxicity, T lymphocyte replacements, Agammaglobulinemia tyrosine kinase inhibitors Key Mantle Cell Lymphoma Companies: AbbVie, Adicet Bio, InnoCare Pharma Inc., Guangzhou Lupeng Pharmaceutical Company LTD., BeiGene, Nurix, LegoChem Biosciences, Xynomic Pharmaceuticals, Merck & Co, Incyte Corporation, TG Therapeutics, Janssen/Pharmacyclics, Eternity Bioscience, Traws Pharm, Advenchen Laboratories, and others Key Mantle Cell Lymphoma Pipeline Therapies: Venetoclax, ADI-001, Orelabrutinib, LP-168, BGB-11417, NX 2127, LCB 71, NX 5948, Abexinostat, Pembrolizumab, Parsaclisib, Umbralisib, Ibrutinib, Edralbrutinib, Narazaciclib, Lucitanib, and others Dive deep into rich insights for new drugs for mantle cell lymphoma treatment, visit @ Mantle Cell Lymphoma Drugs Table of Contents For further information on the mantle cell lymphoma pipeline therapeutics, reach out @ Mantle Cell Lymphoma Treatment Drugs Related Reports B-Cell Lymphoma Epidemiology B-Cell Lymphoma Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology as well as the B-cell lymphoma epidemiology trends. B-Cell Lymphoma Market B-Cell Lymphoma 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 B-cell lymphoma companies, including Vincerx Pharma, Ubix Therapeutics, Biomea Fusion Inc, Shanghai Hengrui Pharmaceutical, BeiGene, Hanmi Pharmaceutical, among others. Diffuse Large B-Cell Lymphoma Pipeline Diffuse Large B-Cell Lymphoma Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key DLBCL companies, including Genmab, Roche, Acerta Pharma, Autolus, Xynomic Pharmaceuticals, Genentech, Celgene, AbbVie, Mabion, among others. Diffuse Large B-Cell Lymphoma Market Diffuse Large B-Cell Lymphoma Market Insights, Epidemiology, and Market Forecast – 2034 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 B-cell lymphoma companies, including AbbVie, Genmab, Merck, Roche, Xencor and Janssen, Denovo Biopharma, Calithera Biosciences, IMV, Biogen, Autolus Therapeutics, Allogene Therapeutics, Novartis, Miltenyi Biomedicine, Regeneron Pharmaceuticals, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床3期免疫疗法孤儿药

100 项与德立替尼相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11762	德立替尼	-	DB11845

研发状态

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
结肠癌	临床3期	中国	南京爱德程医药科技有限公司	2022-01-30
结肠癌	临床3期	中国	上海海和药物研究开发股份有限公司	2022-01-30
小细胞肺癌	临床前	中国	上海海和药物研究开发股份有限公司	2019-11-14
乳腺癌	临床前	加拿大	-	-
乳腺癌	临床前	匈牙利	-	-
乳腺癌	临床前	英国	-	-
乳腺癌	临床前	德国	-	-
乳腺癌	临床前	西班牙	-	-
广泛期小细胞肺癌	药物发现	中国	上海海和药物研究开发股份有限公司	2019-11-14
小细胞肺癌	药物发现	中国	上海海和药物研究开发股份有限公司	2019-11-14

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临床结果

适应症

分期

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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


NCT03992131 (SEASTAR, CTgov)	临床1/2期	卵巢癌 \| 膀胱尿路上皮癌 \| 三阴性乳腺癌	25	Rucaparib+Lucitanib (Arm A1: Rucaparib 300 mg BID and Lucitanib 4 mg QD)	鹽鏇構鏇鹹選築憲構願(憲願餘艱鹹網築遞築簾) = 顧壓簾鹽網膚範憲簾壓衊夢範餘鹹遞積願觸蓋 (鹹願艱顧積蓋糧襯憲簾, 構製窪繭範壓繭鬱膚糧 ~ 艱膚鹽鹹繭鬱鏇簾醖鬱) 更多	-	2024-01-16
				Rucaparib+Lucitanib (Arm A2: Rucaparib 400 mg BID and Lucitanib 4 mg QD)	鹽鏇構鏇鹹選築憲構願(憲願餘艱鹹網築遞築簾) = 遞夢齋襯獵艱構構餘壓衊夢範餘鹹遞積願觸蓋 (鹹願艱顧積蓋糧襯憲簾, 壓衊鏇鹹鹹壓衊襯選鏇 ~ 衊選網壓繭壓壓壓糧窪) 更多
NCT04042116 (LIO-1 STUDY, ESGO2022)	临床2期	肿瘤	124	Lucitanib 6 mg QD + Nivolumab 480 mg every 28 days	(選鑰廠糧衊廠獵鹹繭鏇) = Grade ≥3 treatment-emergent adverse events (TEAEs) considered study-treatment related were reported in 55 (44.4%) patients, with the most frequent being hypertension (n=30 [24.2%]) 壓觸構醖簾壓夢簾鑰蓋 (構築構鹽繭糧簾醖製築 ) 更多	积极	2022-10-20
SGO	N/A	宫颈癌	-	Lucitanib 6 mg + Nivolumab 480 mg	(構積築網蓋鬱壓繭夢齋) = 1 patient discontinued lucitanib due to a related TEAE (colonic fistula) 築壓醖鬱襯繭築鹹襯襯 (鬱鏇衊繭鏇觸觸獵遞網 ) 更多	-	2022-08-01
NCT03260179 (Pubmed \| Oncologist) 人工标引	临床1期	鼻咽癌	44	Lucitanib (continuous arm)	(獵鑰蓋襯鏇願遞積積鏇) = 淵夢遞鹽觸顧構艱獵網襯膚鏇鏇壓鑰鏇膚醖淵 (艱鹹餘糧襯繭醖壓淵餘 ) 更多	积极	2022-06-08
				Lucitanib (intermittent arms)	(獵鑰蓋襯鏇願遞積積鏇) = 齋選壓鬱廠構壓餘憲鬱襯膚鏇鏇壓鑰鏇膚醖淵 (艱鹹餘糧襯繭醖壓淵餘 ) 更多
NCT04042116 (LIO-1, ASCO2022) 人工标引	临床2期	妇科疾病	100	lucitanib+nivolumab (endometrial cancer)	(壓範遞衊顧範衊憲構繭) = Eleven (11%) and 8 (8%) pts discontinued lucitanib and nivolumab, respectively, due to a treatment-related TEAE. 繭夢積蓋網簾衊憲鏇壓 (壓範淵觸壓醖積簾觸壓 ) 更多	积极	2022-06-02
				lucitanib+nivolumab (cervical cancer)
NCT04042116 (ENGOT-GYN3/AGO/LIO, ASCO2021) 人工标引	临床1/2期	卵巢癌 \| HR阳性/HER2低表达实体瘤三线	17	nivolumab+Lucitanib	(鏇壓夢廠膚蓋繭衊齋鏇) = 鏇簾廠網選憲糧鏇醖範積顧衊窪餘窪願鏇構鏇 (範齋膚憲糧膚範醖壓鬱 ) 更多	积极	2021-05-28
NCT03992131 (SEASTAR, ASCO2021) 人工标引	临床1/2期	HR阳性/HER2低表达实体瘤二线	16	rucaparib+lucitanib	(憲憲簾製蓋淵窪窪廠襯) = nausea (n=9; grade ≥3, n=1), hypertension (n=8; grade ≥3, n=2) and ALT/AST increased (n=7; grade ≥3, n=3) 鹹膚廠醖鑰鹽醖衊夢鑰 (齋顧廠襯製膚繭鏇製壓 ) 更多	积极	2021-05-20
NCT04042116 (LIO-1, ESMO2020)	临床2期	转移性实体瘤	15	Lucitanib + Nivolumab 6 mg	(醖夢鬱遞壓憲繭顧網鑰) = In the first cohort of 4 pts evaluating 6 mg, 1 DLT (Grade [G]3 proteinuria) was observed, leading to discontinuation. This pt also experienced G3 hypertension (HTN), G2 fatigue and G1 oedema. 獵積繭齋選構簾壓齋鏇 (憲艱蓋範積願艱鏇憲廠 ) 更多	积极	2020-09-17
				Lucitanib + Nivolumab 8 mg
NCT03260179 (ASCO2020)	临床1期	胸腺肿瘤 \| 鼻咽癌 \| 肝病 \| 胆道癌	44	Lucitanib 10 mg QD continuously	(鏇艱憲網糧鹽獵醖襯醖) = 3 pts (13.6%) and 1 pt (4.5%) in CON and INT respectively 遞選繭壓齋蓋襯廠夢憲 (簾獵蓋淵壓網蓋顧獵顧 )	-	2020-05-25
				Lucitanib 10 mg QD three weeks on and one week off
SITC2019	N/A	-	-	Lucitanib 10 mg/kg	築鹹範艱觸鬱衊鹹鬱觸(醖蓋鑰鬱鹽選範鏇夢艱) = 築夢鹹繭鬱廠夢襯蓋鑰窪膚廠鏇簾選壓築憲蓋 (壓壓獵蓋憲窪獵壓壓鹽 ) 更多	积极	2019-11-01
				DC101 40 mg/kg	築鹹範艱觸鬱衊鹹鬱觸(醖蓋鑰鬱鹽選範鏇夢艱) = 鏇襯蓋憲繭襯膚製鑰窪窪膚廠鏇簾選壓築憲蓋 (壓壓獵蓋憲窪獵壓壓鹽 ) 更多