A Multicenter, Dose-Escalation, Phase 1 Study of Samalizumab (ALXN6000) to Evaluate the Pharmacokinetics, Safety, and Tolerability in Patients With Advanced Cancer

This is a multicenter, open-label, dose-escalation, Phase 1 study of intravenous (IV) samalizumab to determine its maximum tolerated dose (MTD), overall safety/tolerability, pharmacokinetic and pharmacodynamic parameters, and efficacy in participants with advanced cancer. The study was terminated for administrative reasons and not due to any safety concerns.

开始日期2016-11-17

申办/合作机构

Alexion Pharmaceuticals, Inc.

[+1]

NCT00648739 / Terminated临床1/2期

A Phase I/II Open Label Study To Evaluate The Safety, Pharmacokinetics And Pharmacodynamics Of ALXN6000 In Patients With Relapsing Or Refractory B-Cell Chronic Lymphocytic Leukemia Or Multiple Myeloma

The purpose of this study was to determine the safety and maximum tolerated dose (MTD) of ALXN6000 (samalizumab) in treating relapsing or refractory B-cell chronic lymphocytic leukemia (B-CLL) or multiple myeloma (MM) and to study how samalizumab may help the immune system fight tumors that express CD200.

开始日期2008-06-19

申办/合作机构

Alexion Pharmaceuticals, Inc.

100 项与 Samalizumab 相关的临床结果

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100 项与 Samalizumab 相关的转化医学

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100 项与 Samalizumab 相关的专利（医药）

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项与 Samalizumab 相关的文献（医药）

2023-02-04·Oncotarget

The immunoregulatory protein CD200 as a potentially lucrative yet elusive target for cancer therapy

Review

作者: Shao, Anqi ; Owens, David M.

CD200 is an immunoregulatory cell surface ligand with proven pro-tumorigenic credentials via its ability to suppress CD200 receptor (CD200R)-expressing anti-tumor immune function. This definitive role for the CD200-CD200R axis in regulating an immunosuppressive tumor microenvironment has garnered increasing interest in CD200 as a candidate target for immune checkpoint inhibition therapy. However, while the CD200 blocking antibody samalizumab is still in the early stages of clinical testing, alternative mechanisms for the pro-tumorigenic role of CD200 have recently emerged that extend beyond direct suppression of anti-tumor T cell responses and, as such, may not be susceptible to CD200 antibody blockade. Herein, we will summarize the current understanding of CD200 expression and function in the tumor microenvironment as well as alternative strategies for potential neutralization of multiple CD200 mechanisms in human cancers.

2019-12-01·Journal for ImmunoTherapy of Cancer2区 · 医学

Phase I study of samalizumab in chronic lymphocytic leukemia and multiple myeloma: blockade of the immune checkpoint CD200

2区 · 医学

ArticleOA

作者: Faas, Susan J ; Whelden, Maria ; Bedrosian, Camille L ; Farber, Charles ; Mahadevan, Daruka ; Lanasa, Mark C ; Ulery, Terrie ; Zhang, Xiaoping ; Li, Lan ; Pandey, Manjari ; Kukreja, Anjli ; Heffner, Leonard T

PURPOSESamalizumab is a novel recombinant humanized monoclonal antibody that targets CD200, an immunoregulatory cell surface member of the immunoglobulin superfamily that dampens excessive immune responses and maintains self-tolerance. This first-in-human study investigated the therapeutic use of samalizumab as a CD200 immune checkpoint inhibitor in chronic lymphocytic leukemia (CLL) and multiple myeloma (MM).EXPERIMENTAL DESIGNTwenty-three patients with advanced CLL and 3 patients with MM were enrolled in an open-label phase 1 study (NCT00648739). Patients were assigned sequentially to one of 7 dose level cohorts (50 to 600 mg/m²) in a 3 + 3 study design, receiving a single dose of samalizumab intravenously once every 28 days. Primary endpoints were safety, identification of the maximum tolerated dose (MTD), and pharmacokinetics. Secondary endpoints were samalizumab binding to CD200, pharmacodynamic effects on circulating tumor cells and leukocyte subsets, and clinical responses.RESULTSTwenty-one patients received > 1 treatment cycle. Adverse events (AEs) were generally mild to moderate in severity. Samalizumab produced dose-dependent decreases in CD200 expression on CLL cells and decreased frequencies of circulating CD200 + CD4+ T cells that were sustained at higher doses. The MTD was not reached. Decreased tumor burden was observed in 14 CLL patients. One CLL patient achieved a durable partial response and 16 patients had stable disease. All MM patients had disease progression.CONCLUSIONSSamalizumab had a good safety profile and treatment was associated with reduced tumor burden in a majority of patients with advanced CLL. These preliminary positive results support further development of samalizumab as an immune checkpoint inhibitor.TRIAL REGISTRATIONClinicalTrials.gov, NCT00648739 registered April 1, 2008.

100 项与 Samalizumab 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D09961	Samalizumab	-	DB12636

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
急性髓性白血病	临床2期	-	The Leukemia & Lymphoma Society of Canada	-
急性髓性白血病	临床2期	-	Alexion Pharmaceuticals, Inc.	-
晚期癌症	临床前	美国	Alexion Pharmaceuticals, Inc.	2016-11-17
晚期恶性实体瘤	临床前	美国	Alexion Pharmaceuticals, Inc.	2016-11-17
难治性慢性淋巴细胞白血病	临床前	美国	Alexion Pharmaceuticals, Inc.	2008-06-19
慢性淋巴细胞白血病	临床前	美国	Alexion Pharmaceuticals, Inc.	2008-06-19
多发性骨髓瘤	临床前	美国	Alexion Pharmaceuticals, Inc.	2008-06-19

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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


NCT00648739 (Pubmed \| J Immunother Cancer) 人工标引	临床1/2期	慢性淋巴细胞白血病 \| 多发性骨髓瘤	26	samalizumab	(憲鹽齋醖夢膚鹽顧糧衊) = generally mild to moderate in severity 窪遞糧築艱構窪壓鹽鏇 (膚觸鏇廠鏇範積餘顧製 )	积极	2019-08-23
NCT00648739 (CTgov)	临床1/2期	多发性骨髓瘤 \| 难治性慢性淋巴细胞白血病	26	Samalizumab	鑰鹽積襯選獵蓋選選膚(願廠築膚鑰製顧簾鹹選) = 願獵觸壓範顧憲壓鹹廠觸遞淵憲網膚範選艱鏇 (鹽鬱鬱鹹夢艱憲獵淵範, 鹹網壓窪製觸鑰構衊夢 ~ 簾醖夢觸觸蓋餘築憲糧)	-	2019-03-05