babyvot 发表于 2013-5-24 19:47 static/image/common/back.gif
用的人好像不多。。。。。。。
关注一下。。。。。
关注一下。。。。。
Cytotoxic Activity of Tivantinib (ARQ 197) Is Not Due Solely to c-MET Inhibition
http://cancerres.aacrjournals.org/content/73/10/3087.abstract
The receptor tyrosine kinase c-MET is the high-affinity receptor for the hepatocyte growth factor (HGF). The HGF/c-MET axis is often dysregulated in tumors. c-MET activation can be caused by MET gene amplification, activating mutations, and auto- or paracrine mechanisms. Thus, c-MET inhibitors are under development as anticancer drugs. Tivantinib (ARQ 197) was reported as a small-molecule c-MET inhibitor and early clinical studies suggest antitumor activity. To assess whether the antitumor activity of tivantinib was due to inhibition of c-MET, we compared the activity of tivantinib with other c-MET inhibitors in both c-MET–addicted and nonaddicted cancer cells. As expected, other c-MET inhibitors, crizotinib and PHA-665752, suppressed the growth of c-MET-addicted cancers, but not the growth of cancers that are not addicted to c-MET. In contrast, tivantinib inhibited cell viability with similar potency in both c-MET-addicted and nonaddicted cells. These results suggest that tivantinib exhibits its antitumor activity in a manner independent of c-MET status. Tivantinib treatment induced a G2–M cell-cycle arrest in EBC1 cells similarly to vincristine treatment, whereas PHA-665752 or crizotinib treatment markedly induced G0–G1 cell-cycle arrest. To identify the additional molecular target of tivantinib, we conducted COMPARE analysis, an in silico screening of a database of drug sensitivities across 39 cancer cell lines (JFCR39), and identified microtubule as a target of tivantinib. Tivantinib-treated cells showed typical microtubule disruption similar to vincristine and inhibited microtubule assembly in vitro. These results suggest that tivantinib inhibits microtubule polymerization in addition to inhibiting c-MET. Cancer Res; 73(10); 3087–96. ©2013 AACR.
联系了几个有arq197的厂家，都贵的很，说是很难合成。
关注中........
每月1684800元。。。。
168万？？真的吗？
Tivantinib进行中的III期试验进展
ArQule Provides Updates on Clinical Trials in Hepatocellular Carcinoma and Non-Small Cell Lung Cancer with Tivantinib
Data Monitoring Committee approves continuation of Phase 3 METIV-HCC liver cancer trial following safety and pharmacokinetic analyses Asian partner Kyowa Hakko Kirin provides top-line data on ATTENTION trial in non-squamous non-small cell lung cancer
WOBURN, Mass., Jan 16, 2014 (BUSINESS WIRE) -- ArQule, Inc. ARQL -3.60%today provided clinical updates on the ongoing pivotal Phase 3 METIV-HCC trial in hepatocellular carcinoma (liver cancer) conducted by the Company and its partner, Daiichi Sankyo Co., Ltd., and on the completed amended Phase 3 ATTENTION trial in non-squamous non-small cell lung cancer (NSCLC) conducted in Asian territories by its partner, Kyowa Hakko Kirin Co., Ltd.
METIV-HCC Trial
III期肝细胞癌试验
The Data Monitoring Committee (DMC) of the METIV-HCC trial has recommended continuation of the ongoing pivotal Phase 3 METIV-HCC trial of tivantinib as a single agent in hepatocellular carcinoma with a lower dose of tivantinib, 120 milligrams (mg) tablets administered twice daily (BID). This decision followed the DMC’s review of data analyses from a predefined number of patients who received this lower dose.
数据监察委员会推荐继续试验，降低剂量为120mg每日两次。
Recently completed safety analyses among patients treated with 120 mg BID tivantinib tablets showed that the incidence of neutropenia was reduced with this lower dose. In addition, pharmacokinetic analyses from this patient cohort, reviewed by the DMC, demonstrated that the plasma exposure of the 120 mg BID tablets dose was comparable to the exposure achieved with the 240 mg BID capsules dose employed in the Phase 2 trial, with similar medians and overlapping ranges.
最近的分析显示120mg每日两次的较低剂量能降低中性粒减少的发生。药代动力学显示120mg与II期临床中使用的240mg剂量血浆暴露类似。
A dose reduction from 240 mg BID tablets to 120 mg tablets BID was implemented in September, 2013 following the observation of a higher incidence of neutropenia in the initial phase of the METIV-HCC trial than was observed in the Phase 2 trial in the same patient population where a 240 mg BID capsule dose was administered. Certain enhanced patient monitoring procedures had been temporarily instituted to confirm the safety profile of the lower dose.
剂量降低从2013年九月开始实施，此前发现中性粒减少的发生比在II期临床中观察到的要多。
The METIV-HCC trial is a pivotal randomized, double-blind study of tivantinib as single agent therapy in previously treated patients with MET diagnostic-high, inoperable HCC. The primary endpoint is overall survival in the intent-to-treat population, and the secondary endpoint is progression free survival in the same population. METIV-HCC is being conducted under a Special Protocol Assessment (SPA).
METIV-HCC是一项关键性的双盲随机试验，研究tivantinib作为单药治疗曾经接受过治疗的MET高表达的肝细胞癌患者。主要终点是愿意治疗人群的总生存期，次要终点是无进展生存期。
本帖最后由 shany 于 2014-2-6 13:15 编辑
继续上贴
ATTENTION Trial
非小细胞肺癌III期试验
Kyowa Hakko Kirin has provided the Company with top-line results of the amended Phase 3 ATTENTION clinical trial evaluating the combination of tivantinib (ARQ 197) and erlotinib in patients with advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) with wild-type EGFR (epidermal growth factor receptor) in Asia (Japan, Korea and Taiwan).
III期临床ATTENTION评估联合tivantinib和厄洛替尼在亚洲EGFR野生型晚期非鳞非小细胞癌患者中的疗效。
Enrollment in ATTENTION had been originally planned for 460 patients, and the trial’s statistical analysis plan was calibrated accordingly and remained unchanged. Recruitment of new patients was permanently suspended in October, 2012 based on a recommendation by the trial’s Safety Review Committee following an observed imbalance in interstitial lung disease (ILD) cases as a drug-related adverse event. Patients who received treatment in ATTENTION as of October, 2012 were allowed to continue thereafter in the trial after being re-consented, and including such patients, a total of 307 patients were included in the final analysis.
该实验原计划入组460名患者，但在2012年十月中止了入组计划，原因是安全评估委员会发现药物相关的间质性肺炎发生率不平衡。2012年十月以前开始治疗的患者在自愿的前提下被允许继续治疗，最终分析包括307名患者。
In the ITT population, overall survival (OS) favored the treatment arm of tivantinib plus erlotinib compared to the erlotinib only control arm, but it was not statistically significant (median OS of 12.9 months vs 11.2 months, hazard ratio = 0.89, p = 0.4). Progression free survival (PFS) and overall response rate (ORR) results also showed a numerical trend toward improvement favoring the treatment arm.
在愿意接受治疗的人群中，联合治疗组总生存期高于厄洛替尼单药组，但无统计显著差异（12.9个月对比11.2个月）。无进展生存期和总响应率也类似。
The safety profile observed in ATTENTION was in line with what had been previously observed in other NSCLC trials with tivantinib, with the exception of a reported imbalance in ILD, which is a known adverse event in Japanese patients treated with EGFR inhibitors such as erlotinib. In the Phase 3 MARQUEE trial in non-squamous NSCLC conducted in Western countries, no imbalance was observed in the incidence of ILD between treatment and control arms, with one case (0.2%) reported in the treatment arm and four cases (0.8%) in the control arm.
除外间质性肺炎，该实验观察到的安全性跟此前其他tivantinib用于非小细胞癌的试验一致。间质性肺炎对于接受EGFR抑制剂的日本患者来说是一个已知的副作用。在针对西方人群的非鳞非小细胞癌的III期试验MARQUEE中没有观察到治疗组和对照组之间间质性肺炎发生率的不平衡。
ATTENTION is a Phase 3 randomized, double-blind trial comparing OS of second or third line non-squamous NSCLC patients with wild-type EGFR treated with tivantinib and erlotinib to OS of patients treated with placebo and erlotinib. Complete data from this study, including biomarker analyses, are expected to be presented at a future scientific meeting.