AC-480(AC-480) - 药物靶点：EGFR x HER2_专利_临床

概要

基本信息

药物类型

小分子化药

别名

+ [1]

靶点

EGFR x HER2

作用机制

EGFR拮抗剂(表皮生长因子受体erbB1拮抗剂)、HER2拮抗剂(受体蛋白酪氨酸激酶 erbB-2拮抗剂)

治疗领域

肿瘤神经系统疾病

在研适应症-

非在研适应症

晚期恶性实体瘤HER2表达癌症脑恶性胶质瘤+ [3]

原研机构

Bristol Myers Squibb Co.

在研机构-

非在研机构

Ambit Biosciences Corp.

Bristol Myers Squibb Co.

最高研发阶段无进展临床1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

分子式C27H28ClFN8O3

InChIKeyCOUSSRGSHIJMMN-FTBISJDPSA-N

CAS号873837-23-1

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关联

4

项与 AC-480 相关的临床试验

NCT01245543 / Withdrawn临床1期

Open-label, Phase 1 Trial to Evaluate the Safety and Pharmacokinetic Parameters of a 2-day Pulse of Intravenous (IV) AC480 (AC480IV) Administered as Monotherapy and in Combination With Docetaxel in Patients With Advanced Solid Tumors

AC480IV will be administered as a monotherapy and then in combination with docetaxel in patients with locally advanced or metastatic solid tumors for whom there are no standard or curative therapies available. It is designed to evaluate the safety and pharmacokinetic parameters of AC480IV as monotherapy and also in combination with docetaxel under the conditions of the study.

开始日期2010-11-01

申办/合作机构

Daiichi Sankyo, Inc.

NCT00979173 / Completed临床1期IIT

A Pharmacokinetic Study of AC480 Administered Twice Daily in Surgically Resectable Malignant Glioma Patients Not on Enzyme-Inducing Anticonvulsants

The primary objective is to evaluate the intratumoral and plasma pharmacokinetics of AC480 among patients who are candidates for a resection with a recurrent malignant glioma who are not on CYP-3A enzyme inducing anti-epileptic drugs (EIAEDS). Secondary objectives include the following: to evaluate the antiproliferative effect of AC480 by FDG-PET Scan; to evaluate the safety and tolerability of AC480; and, to describe 6-month progression-free survival (PFS) and radiographic response.
This is a single institution, open label, pharmacokinetic study of AC480 in patients with recurrent malignant glioma. The study will enroll 5 patients who are not on enzyme inducing anti-epileptic drugs (EIAEDs) and are scheduled to undergo salvage surgical resection for preoperative treatment with AC480 at 300 mg orally twice daily (BID) for 14 (plus or minus 2) days before surgery (Part I- Induction Therapy). After surgery (Part II- Maintenance Therapy), patients will continue to be dosed with AC480 until disease progression or intolerance, and will be evaluated after every other cycle (1 cycle is 28 days).

开始日期2009-11-01

申办/合作机构

Duke University

[+1]

NCT00207012 / Completed临床1期

Continuous Dosing Phase I Study of BMS-599626 in Patients With HER2-Expressing Advanced Solid Malignancies

This is a continuous dosing Phase I Study of BMS-599626 in patients with HER2-expressing advanced solid malignancies.

开始日期2004-05-01

申办/合作机构

Bristol Myers Squibb Co.

100 项与 AC-480 相关的临床结果

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100 项与 AC-480 相关的转化医学

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100 项与 AC-480 相关的专利（医药）

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150

项与 AC-480 相关的文献（医药）

2023-11-24·Circulation Journal

Relationship Between Direct Oral Anticoagulant Doses and Clinical Outcomes in Elderly Patients With Non-Valvular Atrial Fibrillation　― ANAFIE Registry Sub-Analysis ―

Article

作者: Okumura, Ken ; Tsutsui, Hiroyuki ; Ikeda, Takanori ; Takita, Atsushi ; Yamashita, Takeshi ; Hirayama, Atsushi ; Toyoda, Kazunori ; Yasaka, Masahiro ; Atarashi, Hirotsugu ; Morishima, Yoshiyuki ; Kimura, Tetsuya ; Yamaguchi, Takenori ; Koretsune, Yukihiro ; Suzuki, Shinya ; Teramukai, Satoshi ; Shimizu, Wataru ; Inoue, Hiroshi ; Akao, Masaharu

BACKGROUNDThis sub-analysis of the ANAFIE Registry, a prospective, observational study of >30,000 Japanese non-valvular atrial fibrillation (NVAF) patients aged ≥75 years, assessed the prevalence of direct oral anticoagulant (DOAC) under-dose prevalence, identified the factors of under-dose prescriptions, and examined the relationship between DOAC dose and clinical outcomes.Methods and Results: Patients, divided into 5 groups by DOAC dose (standard, over-, reduced, under-, and off-label), were analyzed for background factors, cumulative incidences, and clinical outcome risk. Endpoints were stroke/systemic embolic events (SEE), major bleeding, and all-cause death during the 2-year follow-up. Of 18,497 patients taking DOACs, 20.7%, 3.8%, 51.6%, 19.6%, and 4.3%, were prescribed standard, over-, reduced, under-, and off-label doses. Factors associated with under-dose use were female sex, age ≥85 years, reduced creatinine clearance, history of major bleeding, polypharmacy, antiplatelet agents, heart failure, dementia, and no history of catheter ablation or cerebrovascular disease. After confounder adjustment, under-dose vs. standard dose was not associated with the incidence of stroke/SEE or major bleeding but was associated with a higher mortality rate. Patients receiving an off-label dose showed similar tendencies to those receiving an under-dose; that is, they showed the highest mortality rates for stroke/SEE, major bleeding, and all-cause death.CONCLUSIONSInappropriate low DOAC doses (under- or off-label dose) were not associated with stroke/SEE or major bleeding but were associated with all-cause death.

2023-10-01·Advances in therapy

Unintended Consequences of Increased Out-of-Pocket Costs During Medicare Coverage Gap on Anticoagulant Discontinuation and Stroke.

Article

作者: Kharat, Akshay ; Greatsinger, Alexandra ; Laliberté, François ; Lefebvre, Patrick ; Jian-Yu, E ; Desai, Urvi ; Zacharia, Nina ; Bookhart, Brahim ; Salam, Tabassum

INTRODUCTIONThis study aims to assess the risk of direct oral anticoagulant (DOAC) discontinuation among Medicare beneficiaries with non-valvular atrial fibrillation (NVAF) who reach the Medicare coverage gap stratified by low-income subsidy (LIS) status and the impact of DOAC discontinuation on rates of stroke and systemic embolism (SE) among beneficiaries with increased out-of-pocket (OOP) costs due to not receiving LIS.METHODSIn this retrospective cohort study, Medicare claims data (2015-2020) were used to identify beneficiaries with NVAF who initiated rivaroxaban or apixaban and entered the coverage gap during ≥ 1 year. DOAC discontinuation rates during the coverage gap were stratified by receipt of Medicare Part D Low-Income Subsidy (LIS), a proxy for not experiencing increased OOP costs. Among non-LIS beneficiaries, incidence rates of stroke and SE during the subsequent 12 months were compared between beneficiaries who did and did not discontinue DOAC in the coverage gap.RESULTSAmong 303,695 beneficiaries, mean age was 77.3 years, and 28% received LIS. After adjusting for baseline differences, non-LIS beneficiaries (N = 218,838) had 78% higher risk of discontinuing DOAC during the coverage gap vs. LIS recipients (adjusted hazard ratio [aHR], 1.78; 95% CI [1.73, 1.82]). Among non-LIS beneficiaries, DOAC discontinuation during coverage gap (N = 91,397; 34%) was associated with 14% higher risk of experiencing stroke and SE during the subsequent 12 months (aHR, 1.14; 95% CI [1.08, 1.20]).CONCLUSIONIncreased OOP costs during Medicare coverage gap were associated with higher risk of DOAC discontinuation, which in turn was associated with higher risk of stroke and SE among beneficiaries with NVAF.

2023-09-01·Current Oncology Reports

Direct Oral Anticoagulants for Cancer-Associated Venous Thromboembolism

Review

作者: Porto, Italo ; Spallarossa, Paolo ; Toma, Matteo ; Masini, Marta ; Ameri, Pietro

AbstractPurpose of ReviewTo present the randomized controlled trial (RCT) evidence and highlight the areas of uncertainty regarding direct oral anticoagulants (DOAC) for cancer-associated venous thromboembolism (CAT).Recent FindingsIn the last years, four RCTs have shown that rivaroxaban, edoxaban, and apixaban are at least as effective as low-molecular-weight heparin (LMWH) for the treatment of both incidental and symptomatic CAT. On the other hand, these drugs increase the risk of major gastrointestinal bleeding in patients with cancer at this site. Another two RCTs have demonstrated that apixaban and rivaroxaban also prevent CAT in subjects at intermediate-to-high risk commencing chemotherapy, albeit at the price of higher likelihood of bleeding. By contrast, data are limited about the use DOAC in individuals with intracranial tumors or concomitant thrombocytopenia. It is also possible that some anticancer agents heighten the effects of DOAC via pharmacokinetic interactions, up to making their effectiveness-safety profile unfavorable.SummaryLeveraging the results of the aforementioned RCTS, current guidelines recommend DOAC as the anticoagulants of choice for CAT treatment and, in selected cases, prevention. However, the benefit of DOAC is less defined in specific patient subgroups, in which the choice of DOAC over LMWH should be carefully pondered.

100 项与 AC-480 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12318

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
脑恶性胶质瘤	临床1期	美国	Ambit Biosciences Corp.	2009-11-01
复发性胶质瘤	临床1期	美国	Ambit Biosciences Corp.	2009-11-01
HER2表达癌症	临床1期	法国	Bristol Myers Squibb Co.	2004-05-01
HER2表达癌症	临床1期	西班牙	Bristol Myers Squibb Co.	2004-05-01
难治恶性实体肿瘤	临床1期	法国	Bristol Myers Squibb Co.	2004-05-01
难治恶性实体肿瘤	临床1期	西班牙	Bristol Myers Squibb Co.	2004-05-01
晚期恶性实体瘤	临床1期	美国	Bristol Myers Squibb Co.	2004-03-01
肿瘤转移	临床1期	美国	Bristol Myers Squibb Co.	2004-03-01

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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


ASCO2005	临床1期	转移性实体瘤	13	BMS-599626	顧觸積齋製遞淵範齋窪(遞壓鹹獵網選憲觸網願) = 蓋衊願窪鑰廠鬱襯糧憲鑰齋鏇顧蓋範鏇觸糧選 (齋鬱憲鏇選繭淵構艱齋 ) 更多	-	2005-06-01
ASCO2005	临床1期	HR阳性/HER2低表达实体瘤	-	BMS-599626	鹹蓋餘廠顧簾鑰醖醖積(構艱築願鹹遞糧壓夢積) = 築構繭鹹糧餘糧製獵廠艱遞範糧鹽襯鏇願夢淵 (鹽蓋選鏇憲範積衊廠餘 ) 更多	-	2005-06-01