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[基础知识] 诺华的cMET新药INC280

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308338 243 老马 发表于 2013-4-26 20:34:30 |
老马  博士一年级 发表于 2013-12-17 17:18:53 | 显示全部楼层 来自: 浙江温州
INC280临床剂量是200mg bid,400mg bid,600mgbid。200mg bid组有病人有效果,效果最好是400mgbid组,副作用开始发生在这个剂量,有病人听力下降,可逆,有病人胆红素升高;600mg bid副作用较大。现在临床剂量维持在400mg bid。
个人公众号:treeofhope

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老马  博士一年级 发表于 2013-12-17 17:29:48 | 显示全部楼层 来自: 浙江温州
盐酸盐,胃溶胶囊
平常认真  初中一年级 发表于 2013-12-17 22:58:19 | 显示全部楼层 来自: 广东佛山
很期待有更多新药上市!
草船借箭  超级版主 发表于 2013-12-24 09:36:09 | 显示全部楼层 来自: 山东烟台
CMET药可以单药,可以联egfr药,可以联抗血管药,可以联化疗,可以联PI3K药,另外T90M突变可以和CMET扩增共存,那么INC280是否可以和4002联用。
INC280和其它药联用的剂量应该是多少呢?
夏眠考拉  小学五年级 发表于 2013-12-26 17:21:52 | 显示全部楼层 来自: 江苏苏州
我家已经耳聋了,不怕,只要有希望上
candy06114  初中一年级 发表于 2013-12-26 19:26:23 来自手机 | 显示全部楼层 来自: 浙江宁波
请问老马单药280该多少用量?我妈alk阴性,克有效3个半月,ap无效,有可能是cmet突变。。
lx92  初中二年级 发表于 2014-1-2 22:16:24 | 显示全部楼层 来自: 北京
本帖最后由 lx92 于 2014-1-2 22:17 编辑
一只白杨 发表于 2013-10-12 00:14
确诊耐药后要重新活检,取组织做c-met IHC或FISH,如果阳性才可能入组,最近接连3例病人都取得不错的效果 ...


白杨,你好。

我父亲免疫组化C-MET (++)是否可以理解为C-MET 扩增 ?(看过平安的C-MET扩增的解释,实在愚钝看不懂),是否可以据此判断适用于INC280? 是否还需要进一步做您提到的c-met IHC或FISH基因检测,我今年8月份在北京医科院中科医院并没有看到有这个基因检测项目可以做。下面附上我父亲8月的基因检测和免疫组化结果,谢谢!

基因检测结果:
EGFR第20号外显因子S768I突变,其余没有突变。
KRAS没有突变。
Fish结果:肿瘤细胞中绝大多数信号是融合信号,偶见分离信号,阳性细胞比例6%,提示:未显示ALK(2p23)染色体易位。

免疫组化:
ALK-D5F3 (-); ALK-NEG (-); C-MET (2+); VEGF (-); VEGF2 (2+); VEGF3 (-); HER2 (-); BCL-2 (-)
老马  博士一年级 发表于 2014-1-3 14:53:53 | 显示全部楼层 来自: 浙江温州
A phase I dose-escalation study of INCB028060, an inhibitor of c-MET receptor tyrosine kinase, in patients with advanced solid tumors.
http://meeting.ascopubs.org/cgi/ ... 15_suppl/3091?rss=1
R. C. Donehower, A. Scardina, M. Hill, J. Bowman, R. C. Newton, X. Liu, P. Scherle, Q. Wang, S. Diamond, J. Boer, F. Lee, T. Gau, H. A. Burris, J. C. Bendell, S. F. Jones and J. R. Infante
Background: INCB028060 is a potent and selective inhibitor of c-MET receptor tyrosine kinase (RTK). This first-in-human study aims to determine the maximum tolerated dose (MTD), pharmacokinetics (PK), pharmacodynamics (PD), and potential efficacy of INCB028060. Methods: In a standard 3+3 escalation, patients (pts) age =18 years with advanced solid tumors are treated with INCB028060 orally once (QD) or twice daily on a continuous 28-day schedule. C-MET inhibition is evaluated by adding c-MET overexpressing SNU-5 human gastric cancer cells to pts whole blood and then analyzing for inhibition of phospho-c-MET by ELISA. Results: At this time 17 pts have been treated across dose levels of 10, 20, 50, and 70 mg/once daily. Median age is 63 years, median ECOG PS is 0, and the most common tumor types are colorectal (4), NSCLC (3), and prostate/HCC/cholangiocarcinoma (2 each). One pt with breast cancer and diffuse liver metastases treated at 50 mg QD developed grade 3 AST elevation on C1D22, having had grade 2 AST at baseline; the AST continued to rise once treatment was discontinued. The MTD has not been reached and no other grade 3/4 adverse events (AEs) noted. CTC grade 1-2 AEs considered possibly treatment-related have included mild tremor, fatigue, nausea, diarrhea, indigestion, headache, and agitation. The Cmax and AUC values of INCB028060 have been dose-proportional, with a mean half-life of 6.8 hours. For the 70 mg QD cohort, INCB028060 mean plasma concentrations exceeded IC90 for 17 h of the day. At the 70 mg dose level on day 15, the oral CL was 35.2 (+/- 11.5) L/h and renal clearance was negligible. Dose-dependent reductions in phospho-c-MET levels have been detected on day 15 (pre-dose) by whole blood-based PD analysis, with mean inhibition of 41.3%, 45.7%, 67.5% and 69% at 10, 20, 50 and 70 mg/day, respectively. Conclusions: Thus far, toxicity has been manageable with INCB028060. The PK profile is favorable and supports exploration of a BID schedule. Dose-dependent decreases in phospho-c-MET are promising.
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lx92  初中二年级 发表于 2014-1-12 19:17:48 | 显示全部楼层 来自: 北京
老马 发表于 2014-1-3 14:53
A phase I dose-escalation study of INCB028060, an inhibitor of c-MET receptor tyrosine kinase, in pa ...

老马,能否烦请你解答下我上面的问题,谢谢!
whitesnow777  高中三年级 发表于 2014-1-13 09:42:07 | 显示全部楼层 来自: 山东
夏眠考拉 发表于 2013-12-26 17:21
我家已经耳聋了,不怕,只要有希望上

你好,你家280近期效果如何?还有什么副作用?祝福。

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