依美昔单抗(Ecromeximab) - 药物靶点：GD3_专利_临床

概要

基本信息

药物类型

单克隆抗体

别名

Ecromeximab (USAN/INN)

靶点

GD3

作用机制

GD3抑制剂(神经节苷脂GD3抑制剂)、免疫刺激剂

治疗领域

肿瘤皮肤和肌肉骨骼疾病

在研适应症-

非在研适应症

黑色素瘤皮肤黑色素瘤转移性黑色素瘤

原研机构

Kyowa Kirin Co., Ltd.

在研机构-

非在研机构

Kyowa Kirin, Inc. /Sancuso/

Ludwig Institute for Cancer Research Ltd.Kyowa Kirin Pharmaceutical Development Ltd.

最高研发阶段终止临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

Sequence Code 319922110L

来源: *****

Sequence Code 319922109H

来源: *****

关联

2

项与依美昔单抗相关的临床试验

NCT00679289

/ Completed临床2期IIT

Phase II Study of the Anti-Ganglioside GD3 Mouse/Human Chimeric Antibody KW2871 Combined With High Dose Interferon-α2b in Patients With Metastatic Melanoma

This was a Phase 2, open-label study of KW2871 (ecromeximab) in combination with high-dose interferon-α2b (HDI) in patients with metastatic melanoma. The primary objectives of this study were to assess progression-free survival (PFS) and safety. The secondary objectives were to assess the objective response rate, KW2871 pharmacokinetics (PK), and other exploratory immunology as indicated (e.g., development of human anti-chimeric antibodies [HACA], activity of antibody-dependent cell-mediated cytotoxicity [ADCC] and complement-dependent cytotoxicity [CDC] in peripheral blood, number and functional state of tumor-infiltrating immune cells and expression of GD3 in immune and tumor cells of tumor biopsies, and markers of interferon [IFN] response/resistance and markers of resistance to ADCC/CDC in peripheral blood mononuclear cells [PBMCs]).

开始日期2008-03-28

申办/合作机构

Ludwig Institute for Cancer Research Ltd.

[+3]

NCT00199342

/ Terminated临床1/2期

An Open-Label Study of KW-2871 Administered With a Premedication Regimen in Patients With Advanced Stage IV Melanoma

This is a dose escalating cohort study to determine the maximum tolerated dose (MTD) of KW-2871 (in dose cohorts of 60, 80, and 100 mg/m2) when administered with a specified premedication regimen (ranitidine, diphenhydramine, and dexamethasone). KW-2871 will be administered at 14-day intervals.

开始日期2004-11-01

申办/合作机构

Kyowa Kirin, Inc. /Sancuso/

100 项与依美昔单抗相关的临床结果

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100 项与依美昔单抗相关的转化医学

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100 项与依美昔单抗相关的专利（医药）

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3

项与依美昔单抗相关的文献（医药）

2017-08-01·Melanoma Research4区 · 医学

Safety and efficacy of the antiganglioside GD3 antibody ecromeximab (KW2871) combined with high-dose interferon-α2b in patients with metastatic melanoma

4区 · 医学

Article

作者: Lin, Hui-Min ; Yin, Yan ; Gajewski, Thomas F. ; Kirkwood, John M. ; Venhaus, Ralph ; Sander, Cindy ; Moschos, Stergios J. ; Tarhini, Ahmad A. ; Lin, Yan

This study evaluated the safety and clinical benefit of ecromeximab (KW2871) combined with high-dose interferon-α2b (HDI) in patients with metastatic melanoma. We also carried out pharmacokinetic and immune monitoring studies of this combination. This was an open-label, phase 1/2 study of ecromeximab plus HDI in patients with measurable metastatic melanoma. Eligible patients received ecromeximab-HDI combination therapy: ecromeximab administered intravenously once every 2 weeks and HDI at a dose of 20 million units (MU)/m2 administered intravenously for 5 consecutive days per week for the first 4 weeks (induction phase) and then at 10 MU/m2 subcutaneously thrice weekly through week 14 (maintenance phase). Patients were treated with combination therapy until disease progression or limiting toxicity. Three dose-escalation cohorts (5, 10, and 20 mg/m2) of ecromeximab were planned. Thirty-six evaluable patients were enrolled including six in each of cohorts 1 and 2, and 24 in cohort 3. Median progression-free survival was 2.53 months [95% confidence interval (CI):1.93–3.83] and it was 1.93 months (95% CI: 1.00–3.80) in cohort 3. The median overall survival was 10.28 months (95% CI: 6.93–16.77) and 7.78 months (95% CI: 6.03–13.97) in cohort 3. There was no significant difference in progression-free survival or overall survival by BRAF mutation status. The response rate was 5.6% (95% CI: 0.68–18.7), with two patients showing an objective response (one complete response and one partial response), and the clinical benefit rate was 78% (95% CI: 61–90). Stable disease as best response was observed in 26 (72%) patients including five in each of cohorts 1 and 2, and 16 in cohort 3. Treatment-emergent adverse events considered related to ecromeximab treatment occurred in four (66.7%) patients in cohort 1, five (83.3%) patients in cohort 2, and seven (29.2%) patients in cohort 3. Among TEAEs with a maximum severity of grade 3 or 4, those that occurred only in cohort 3 were related to pain, electrolyte imbalance, blood cell decreases, and allergic reaction. Safety and efficacies considered related to ecromeximab occurred in cohort 3 and included grade 3 hypersensitivity [one (4.2%)] and grade 2 hypotension [one (4.2%)]. Regimen-limiting toxicities occurred in two (8.3%) patients in cohort 3: hypersensitivity (with hypertension, supraventricular tachycardia, bronchospasm, chills, and dyspnea) and hypotension. One patient out of 31 examined showed a low-level transient positivity for human antichimeric antibodies against ecromeximab. Pharmacokinetic measurements by enzyme-linked immunosorbent assay determined that administration of HDI does not influence serum levels of ecromeximab at 5, 10, and 20 mg/m2 dose levels. Ecromeximab in combination with HDI was generally well tolerated in patients with metastatic melanoma and has shown low immunogenicity. However, the clinical activity was limited, suggesting that future development of this combination should be deprioritized and that other combinations, such as with immune checkpoint inhibitors, should be considered.

2006-12-01·Cancer Biotherapy and Radiopharmaceuticals4区 · 医学

Anti-GD3 Monoclonal Antibody Effects on Lymphocytes and Antibody-Dependent Cellular Cytotoxicity

4区 · 医学

Article

作者: LoBuglio, Albert F. ; Triozzi, Pierre L. ; Su, Kaihong ; Conry, Robert ; Aldrich, Wayne ; Carlisle, Ronda ; Edberg, Jeffrey C. ; Forero, Andres ; Wang, Wen-Quan ; Shah, Jatin J.

PURPOSEAntibodies targeting GD3 gangliosides highly expressed on melanomas mediate immune effector functions in vitro and inhibit animal model melanoma tumor growth in vivo. Because GD3 is expressed also on a subpopulation of human lymphocytes, we characterized the in vitro immune effects of murine R24 and a chimeric anti-GD3 antibody (KW-2871).DESIGNAnti-GD3 complement-mediated (CMC) and antibody-dependent cellular cytotoxicity (ADCC) were tested against cell line Mel-624. Antibody-mediated lymphocyte expression of interleukin (IL)-2, IL-4, IL-10, and interferon-gamma (IFN-gamma) was quantified. The effect of antibody and antibody-treated lymphocyte supernates on effector cell ADCC and Fc receptor expression were evaluated.RESULTSR24 and KW-2871 antibodies mediated CMC and ADCC to the Mel-624 cell line. R24 induced potent lymphocyte proliferation and enhanced lymphocyte RNA expression of IL-4 (2-4 logs), IL-10, and IFN-gamma (> 10-fold). KW-2871 induced no lymphocyte proliferation and had minimal effects on lymphokine expression (< 5-fold). Preincubation of effector cells with either antibody inhibited ADCC and reduced monocyte expression of FcgammaRI and II. Supernates of effector cells preincubated with either antibody were able to inhibit ADCC.CONCLUSIONSR24 and KW-2871 antibody differ in their lymphocyte proliferation and lymphokine release activity but have similar inhibition of lymphocyte ADCC and FcgammaR expression in vitro.

2006-12-01·Cancer Biotherapy and Radiopharmaceuticals4区 · 医学

A Phase I Study of an Anti-GD3 Monoclonal Antibody, KW-2871, in Patients with Metastatic Melanoma

4区 · 医学

Article

作者: Forero, Andres ; Triozzi, Pierre L. ; Wang, Wen-Quan ; Fujimori, Matt ; Carlisle, Ronda ; Shah, Jatin ; Conry, Robert M. ; LoBuglio, Albert F.

PURPOSEKW-2871 (IgG1 kappa chimeric antibody) targets GD3, which is upregulated in melanomas. We conducted a phase I trial of KW-2871 in patients with metastatic melanoma.METHODSSeventeen (17) patients were enrolled and received an initial test dose (10 mg/m2) intravenously. Two 2 weeks later, patients were stratified into 4 cohorts to receive 4 doses of KW-2871 (infused over 1 hour) at 2-week intervals (20, 40, 60, and 80 mg/m2). No premedications were administered for the test or first therapeutic doses.RESULTSDose-limiting toxicities were Grade 3 laryngospasm and chest tightness with the initial therapeutic infusion at doses of 80 and 60 mg/m2. The maximum tolerated dose (MTD) was established at 40 mg/m2 of KW2871. The most common side-effect was urticaria (Grades 1-3) in 16 of 16 patients during an initial therapeutic infusion without premedication. The mean terminal half-life, clearance, and area under the concentration-time curve (AUC(0-t)) at a dose of 40 mg/m2 for course 1 were 146 +/- 31 hours, 28 +/- 6 ml/hour, and 1922 +/- 491 mcg*hour/mL, respectively. Anti-human chimeric antibody was not detected. Two (2) patients in the 40 mg/m2 cohort had stable disease.CONCLUSIONSAn MTD of 40 mg/m2 without premedication was established for KW-2871, with urticaria being the most common side-effect and dose-limiting anaphylactoid infusion reactions.

100 项与依美昔单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D03939	依美昔单抗	-	DB12797

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
黑色素瘤	临床2期	美国	Kyowa Kirin Pharmaceutical Development Ltd.	2004-11-01
转移性黑色素瘤	临床2期	美国	Kyowa Kirin, Inc. /Sancuso/	2004-11-01
转移性黑色素瘤	临床2期	美国	Kyowa Kirin, Inc. /Sancuso/	2004-11-01
皮肤黑色素瘤	药物发现	美国	Ludwig Institute for Cancer Research Ltd.	2008-03-28

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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


NCT00679289 (CTgov)	临床2期	皮肤黑色素瘤 \| 转移性黑色素瘤	36	HDI+KW2871 (Cohort 3)	襯鑰遞鑰製簾蓋鑰顧壓(獵願壓膚齋壓蓋構鏇蓋) = 蓋選簾繭衊夢糧獵鬱膚壓選網獵廠網獵構構積 (夢積憲廠遞餘構壓鹽廠, 觸觸艱鏇窪蓋餘齋鏇構 ~ 鬱夢觸積願淵顧糧壓糧) 更多	-	2018-02-09
NCT00679289 (CTgov)	临床2期	皮肤黑色素瘤 \| 转移性黑色素瘤	36	HDI+KW2871 (Cohort 1)	鹽淵積鹹遞壓艱廠餘廠(鬱醖憲蓋遞鏇夢餘繭壓) = 鏇觸製壓窪積獵糧醖憲壓範淵網積鬱顧鹽鬱淵 (鹽積夢餘鑰衊糧淵糧願, 糧蓋齋衊獵鑰齋鹽鏇獵 ~ 鹹窪壓衊顧蓋餘淵鬱鬱) 更多	-	2018-02-09
ASCO2005	临床1期	转移性黑色素瘤	17	KW-2871 40 mg/m2	(憲糧選鹽淵膚網鹹構窪) = 壓顧遞鏇遞範獵憲醖範構鬱齋蓋觸憲蓋選積獵 (願蓋簾網糧範衊蓋遞窪 ) 更多	-	2005-06-01