A Phase 3, Randomized, Open-Label, Active-Controlled, Superiority Trial of EG007, Added to the Combination of Lenvatinib Plus Pembrolizumab Vs. Lenvatinib Plus Pembrolizumab in Patients with Advanced Endometrial Cancer

This is a Phase 3, multicenter, randomized, open-label trial to evaluate whether EG-007 plus Len+Pem is superior to Len+Pem alone in patients with advanced endometrial cancer (Stage III or IV). This trial will be preceded by a safety lead-in study with up to 28 patients (the safety lead-in is a separate, free-standing protocol).
Approximately 450 patients will be randomized equally (1:1) to receive EG-007 plus Len+Pem or Len+Pem alone. The randomization will be stratified by the following stratification factors:
* Diagnosis Classification (advanced Stage III/IV vs. recurrent endometrial cancer)
* ECOG score at baseline (0 vs 1)
* Geographic region (Asia vs ROW)

开始日期2025-12-01

申办/合作机构

Evergreen Therapeutics, Inc

100 项与 VEGFR1 x FGFR2 x VEGFR2 x FGFR1 x VEGFR3 相关的临床结果

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100 项与 VEGFR1 x FGFR2 x VEGFR2 x FGFR1 x VEGFR3 相关的转化医学

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0 项与 VEGFR1 x FGFR2 x VEGFR2 x FGFR1 x VEGFR3 相关的专利（医药）

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项与 VEGFR1 x FGFR2 x VEGFR2 x FGFR1 x VEGFR3 相关的文献（医药）

2021-10-11·Biology of Reproduction2区 · 生物学

Chemerin as a modulator of angiogenesis and apoptosis processes in the corpus luteum of pigs: an in vitro study

2区 · 生物学

Article

作者: Smolinska, Nina ; Kiezun, Marta ; Gudelska, Marlena ; Rytelewska, Edyta ; Zaobidna, Ewa ; Dobrzyn, Kamil ; Kisielewska, Katarzyna ; Kaminski, Tadeusz

AbstractThe corpus luteum (CL) undergoes rapid changes, and its functional capabilities are influenced by processes such as angiogenesis and apoptosis. According to the literature, chemerin-a protein that participates in the regulation of energy homeostasis and the immune response, may also affect angiogenesis and apoptosis. Therefore, the aim of this study was to investigate the in vitro effect of chemerin on angiogenesis and apoptosis in porcine luteal cells (Lc) during specific phases related to CL physiology. Luteal cells were harvested from gilts during the early-, mid-, and late-luteal phases of the estrous cycle. The cells were preincubated for 48 h and incubated for 24 h with chemerin or a serum-free medium (controls). The abundance of angiogenesis- and apoptosis-related proteins was determined by enzyme-linked immunosorbent assay (ELISA) in spent culture media, or by ELISA and Western blot in protein extracts. The current study demonstrated that chemerin stimulates the production of vascular endothelial growth factor A (VEGF-A) and basic fibroblast growth factor (bFGF) by porcine Lc and increases the protein abundance of angiogenic factors’ receptors (VEGFR1, VEGFR2, VEGFR3, FGFR1, FGFR2) in these cells. The study also revealed that chemerin exerts a modulatory effect (stimulatory/inhibitory, depending on the phase of the cycle) on the protein abundance of first apoptosis signal (Fas), Fas ligand, B-cell lymphoma 2, and caspase-3 in porcine Lc. These results imply that chemerin may affect angiogenesis and apoptosis processes in the porcine CL, as evidenced by its modulatory effect of chemerin on the protein abundance of crucial angiogenesis- and apoptosis-related factors, observed in an in vitro study of porcine Lc.

2018-06-01·Cancer1区 · 医学

Treatment‐emergent hypertension and efficacy in the phase 3 Study of (E7080) lenvatinib in differentiated cancer of the thyroid (SELECT)

1区 · 医学

Article

作者: Schlumberger, Martin ; Robinson, Bruce ; Kiyota, Naomi ; Wirth, Lori J. ; Guo, Matthew ; Habra, Mouhammed Amir ; Newbold, Kate ; Mathias, Elton ; Francis, Sanjeev ; Brose, Marcia S. ; Tahara, Makoto ; Dutcus, Corina E. ; Sherman, Steven I.

BACKGROUNDHypertension (HTN) is an established class effect of vascular endothelial growth factor receptor (VEGFR) inhibition. In the phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial, HTN was the most frequent adverse event of lenvatinib, an inhibitor of VEGFR1, VEGFR2, VEGFR3, fibroblast growth factor receptor 1 (FGFR1), FGFR2, FGFR3, FGFR4, platelet‐derived growth factor receptor α (PDGFRα), ret proto‐oncogene (RET), and stem cell factor receptor (KIT). This exploratory analysis examined treatment‐emergent hypertension (TE‐HTN) and its relation with lenvatinib efficacy and safety in SELECT.METHODSIn the multicenter, double‐blind SELECT trial, 392 patients with progressive radioiodine‐refractory differentiated thyroid cancer (RR‐DTC) were randomized 2:1 to lenvatinib (24 mg/d on a 28‐day cycle) or placebo. Survival endpoints were assessed with Kaplan‐Meier estimates and log‐rank tests. The influence of TE‐HTN on progression‐free survival (PFS) and overall survival (OS) was analyzed with univariate and multivariate Cox proportional hazards models.RESULTSOverall, 73% of lenvatinib‐treated patients and 15% of placebo‐treated patients experienced TE‐HTN. The median PFS for lenvatinib‐treated patients with (n = 190) and without TE‐HTN (n = 71) was 18.8 and 12.9 months, respectively (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.39‐0.88; P = .0085). For lenvatinib‐treated patients, the objective response rate was 69% with TE‐HTN and 56% without TE‐HTN (odds ratio, 1.72; 95% CI, 0.98‐3.01). The median change in tumor size for patients with and without TE‐HTN was −45% and −40%, respectively (P = .2). The median OS was not reached for patients with TE‐HTN; for those without TE‐HTN, it was 21.7 months (HR, 0.43; 95% CI, 0.27‐0.69; P = .0003).CONCLUSIONSAlthough HTN is a clinically significant adverse event that warrants monitoring and management, TE‐HTN was significantly correlated with improved outcomes in patients with RR‐DTC, indicating that HTN may be predictive for lenvatinib efficacy in this population. Cancer 2018;124:2365‐72. © 2018 American Cancer Society.

2018-01-01·International Journal of Gynecologic Cancer3区 · 医学

Endometrial Cancers Harboring Mutated Fibroblast Growth Factor Receptor 2 Protein Are Successfully Treated With a New Small Tyrosine Kinase Inhibitor in an Orthotopic Mouse Model

3区 · 医学

Article

作者: Maria Reyes ; C. Matthew Peterson ; Margit M. Janát-Amsbury ; Sebastien Taurin ; Theresa L. Werner ; Elke A. Jarboe ; Chieh Hsiang Yang ; Sungpil Cho ; Demetrius M. Coombs

ObjectivesAL3818 (anlotinib) is a receptor tyrosine kinase inhibitor targeting vascular endothelial growth factor receptors (VEGFR1, VEGFR2/KDR, and VEGFR3), stem cell factor receptor (C-kit), platelet-derived growth factor (PDGFβ), and fibroblast growth factor receptors (FGFR1, FGFR2, and FGFR3). This study evaluates the efficacy of AL3818 studying tumor regression in an orthotopic murine endometrial cancer model.MethodsWe tested the cytotoxicity of AL3818 on a panel of 7 human endometrial cancer cell lines expressing either wild-type or mutant FGFR2 and also assessed the in vivo antitumor efficacy in a murine, orthotopic AN3CA endometrial cancer model. AL3818 was administered daily per os either alone or in combination with carboplatin and paclitaxel, which represent the current standard of adjuvant care for endometrial cancer.ResultsAL3818 significantly reduces AN3CA cell number in vitro, characterized by high expression of a mutated FGFR2 protein. Daily oral administration of AL3818 (5 mg/kg) resulted in a complete response in 55% of animals treated and in a reduced tumor volume, as well as decreased tumor weights of AN3CA tumors by 94% and 96%, respectively, following a 29-day treatment cycle. Whereas carboplatin and paclitaxel failed to alter tumor growth, the combination with AL3818 did not seem to exhibit a superior effect when compared with AL3818 treatment alone.ConclusionsAL3818 shows superior efficacy for the treatment of endometrial cancer irresponsive to conventional carboplatin and paclitaxel combination and warrants further investigation.

项与 VEGFR1 x FGFR2 x VEGFR2 x FGFR1 x VEGFR3 相关的新闻（医药）

2024-10-14

·医药观澜

卫材口服癌症新药「仑伐替尼」新适应症在中国申报上市

10月12日，中国国家药监局药品审评中心（CDE）官网公示，卫材（Eisai）申报的甲磺酸仑伐替尼胶囊新适应症上市申请获得受理，具体适应症尚未公示。仑伐替尼为卫材公司研发的一种口服多激酶抑制剂，此前已经在全球范围内获批多项癌症适应症。公开资料显示，仑伐替尼（lenvatinib）是一种口服多种激酶抑制剂，可以选择性抑制多种激酶的活性，包括血管内皮生长因子受体（VEGFR1、VEGFR2和VEGFR3），以及成纤维细胞生长因子受体（FGFR1、FGFR2、FGFR3和FGFR4），此外还有致病性血管生成、肿瘤生长和癌症进展相关受体酪氨酸激酶，如血小板衍生生长因子受体α（PDGFRα）、KIT和RET。仑伐替尼作为单药，已经在日本、美国、欧洲、中国等国家和地区获批用于一线治疗甲状腺癌和肝细胞癌，在日本也被批准用于治疗胸腺癌。仑伐替尼与依维莫司联合疗法已经在美国、欧洲和亚洲等地被批准用于二线治疗肾细胞癌；与抗PD-1单抗帕博利珠单抗组成的联合疗法已经在多地获批用于一线治疗肾细胞癌、既往经过全身治疗的子宫内膜癌等。根据卫材官网最新管线信息，仑伐替尼还有3项国际多中心（含中国）3期临床研究正在进行中，针对适应症包括：联合经动脉化疗栓塞术（TACE）一线治疗肝细胞癌（LEAP-012研究）；联合化疗一线治疗食管癌（LEAP-014）；联合化疗一线治疗胃癌（LEAP-015）。在今年的美国临床肿瘤学会（ASCO）年会上，研究人员还公布了LEAP-012研究的研究结果，该研究旨在评估评估帕博利珠单抗+仑伐替尼联合TACE与双安慰剂+TACE治疗不可切除的非转移性肝细胞癌（HCC）患者的疗效。研究表明，在中位随访25.6个月后，帕博利珠单抗+仑伐替尼联合TACE在无进展生存方面显示出具有统计学意义和临床意义的改善，与单独使用TACE相比，将疾病进展或死亡风险降低了34%。帕博利珠单抗+仑伐替尼方案的中位无进展生存期为14.6个月，而TACE方案的中位无进展生存期为10.0个月。期待仑伐替尼后续临床研究也顺利进行，早日为更多的患者带来新的治疗选择。参考资料： [1]中国国家药监局药品审评中心（CDE）官网. Retrieved Oct 12，2024, From https://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c [2]卫材官网研发管线. Retrieved Aug 2, 2024, from https://www.eisai.com/innovation/research/pipeline/index.html [3]LEAP-012: Pembrolizumab Plus Lenvatinib Added to TACE Improved Progression-Free Survival in HCC. Retrieved Sep 16, 2024, from https://ascopost.com/news/september-2024/leap-012-pembrolizumab-plus-lenvatinib-added-to-tace-improved-progression-free-survival-in-hcc/ 内容来源于网络，如有侵权，请联系删除。