{"id":25700,"date":"2018-08-08T01:00:00","date_gmt":"2018-08-09T03:38:21","guid":{"rendered":"http:\/\/www.05921.net\/index.php\/2018\/08\/09\/%e6%b7%b1%e5%ba%a6%e9%98%85%e8%af%bb%ef%bc%9a-alk%e9%9d%b6%e5%90%91%e8%8d%af%e7%89%a9%e8%b0%83%e7%a0%94%e6%8a%a5%e5%91%8a\/"},"modified":"2018-08-09T11:38:27","modified_gmt":"2018-08-09T03:38:27","slug":"%e6%b7%b1%e5%ba%a6%e9%98%85%e8%af%bb%ef%bc%9a-alk%e9%9d%b6%e5%90%91%e8%8d%af%e7%89%a9%e8%b0%83%e7%a0%94%e6%8a%a5%e5%91%8a","status":"publish","type":"post","link":"https:\/\/www.05921.net\/index.php\/25700\/","title":{"rendered":"\u6df1\u5ea6\u9605\u8bfb\uff1a ALK\u9776\u5411\u836f\u7269\u8c03\u7814\u62a5\u544a"},"content":{"rendered":"
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<\/section>\n<\/section>\n
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\u80ba\u764c\u662f\u5168\u7403\u764c\u75c7\u6b7b\u4ea1\u7684\u4e3b\u8981\u539f\u56e0\uff0c\u4e5f\u662f\u4e2d\u56fd\u764c\u75c7\u4e2d\u7684<\/span>\u201c\u5934\u53f7\u6740\u624b<\/span>\u201d<\/span>\u3002 \u6839\u636e\uff37\uff28\uff2f\u7684\u5206\u7c7b\uff0c\u80ba\u764c\u6309\u7167\u6cbb\u7597\uff0c\u9884\u540e\u53ca\u751f\u7269\u5b66\u7279\u5f81\u5212\u5206\u4e3a\u975e\u5c0f\u7ec6\u80de\u80ba\u764c\uff08<\/span>NSCLC\uff09\u4e0e\u5c0f\u7ec6\u80de\u80ba\u764c\uff08<\/span>SCLC<\/span>\uff09\u3002\u591a\u8fbe<\/span>80%-85%<\/span>\u7684\u80ba\u764c\u75c5\u7406\u7c7b\u578b\u4e3a<\/span>NSCLC<\/span><\/span>\u3002<\/span>
<\/p>\n<\/section>\n<\/section>\n<\/section>\n


<\/p>\n

\u9057\u4f20\u5b66\u7814\u7a76\u8868\u660e\uff0c<\/span>ALK\u7684\u67d3\u8272\u4f53\u91cd\u6392\u662f\u90e8\u5206<\/span><\/span><\/strong> <\/span><\/strong>NSCLC<\/span><\/strong>\u60a3\u8005\u7684\u5173\u952e\u9a71\u52a8\u56e0\u7d20\uff0c<\/span><\/strong>\u7ea6<\/span>3%\u81f3<\/span>5%<\/span>\u7684\u8f6c\u79fb\u6027<\/span><\/span>NSCLC<\/span>\u60a3\u8005\u5177\u6709<\/span>ALK\u57fa\u56e0\u91cd\u6392\u3002<\/span><\/span>\u770b\u4f3c\u6bd4\u4f8b\u4e0d\u7b97\u5f88\u9ad8\uff0c\u4f46\u6bcf\u5e74\u7684\u65b0\u53d1\u75c5\u4f8b\u975e\u5e38\u591a\uff0c\u636e\u4e00\u9879\u5168\u7403<\/span>27\u4e2a\u4e2d\u5fc3\u7684\u6570\u636e\uff0c\u6bcf\u5e74\u5168\u4e16\u754c\u65b0\u53d1\u75c5\u4f8b<\/span>130<\/span>\u4e07\uff0c\u5176\u4e2d\uff0c\u6709<\/span>6<\/span>\u4e07\u4ee5\u4e0a\u7684\u60a3\u8005\u5b58\u5728<\/span>ALK<\/span>\u91cd\u6392\uff0c\u8fd8\u4ee5\u5f88\u5feb\u7684\u901f\u5ea6\u5728\u589e\u52a0\u3002<\/span><\/span>\u76ee\u524d\uff0c<\/span>\u9488\u5bf9<\/span>ALK<\/span>\u57fa\u56e0\u7684\u9776\u70b9\u836f\u7269\u7684\u53d1\u5c55\u3002\u5982\u4e0b\u8868\u6240\u8ff0\u3002<\/span><\/p>\n


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\"\u6df1\u5ea6\u9605\u8bfb\uff1a<\/p>\n


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\u672c\u6587\u9610\u8ff0\u4e86\u76ee\u524d\u4e0a\u5e02\u7684\u548c\u5373\u5c06\u4e0a\u5e02<\/span>ALK<\/span>\u9776\u5411\u836f\u7269\u7684\u57fa\u672c\u7684\u4fe1\u606f<\/span>\uff0c\u4e3a<\/span>ALK\u878d\u5408\u57fa\u56e0\u7684\u7684\u9776\u5411<\/span><\/span>\u836f\u7269\u63d0\u4f9b\u4f9d\u636e\u3002<\/o:p><\/span><\/span><\/p>\n


<\/p>\n

\n
\u7b2c\u4e00\u4ee3 ALK\u6291\u5236\u5242\u2014\u514b\u5511\u66ff\u5c3c<\/span><\/section>\n
<\/section>\n
<\/section>\n<\/section>\n


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\"\u6df1\u5ea6\u9605\u8bfb\uff1a<\/p>\n


<\/p>\n

\u514b\u5511\u66ff\u5c3c\u4f5c\u4e3a<\/span>\u9996\u4e2a<\/span><\/strong>\u9488\u5bf9<\/span> ALK \u9633\u6027 <\/span>NSCLC <\/span>\u5f00\u53d1\u7684\u5c0f\u5206\u5b50\u916a\u6c28\u9178\u6fc0\u9176\u6291\u5236\u5242\uff0c\u9996\u5148\u4e8e <\/span><\/span>2011 \u5e74 <\/span>8 <\/span>\u6708 <\/span>26 <\/span>\u65e5\u5728\u7f8e\u56fd\u6309\u52a0\u901f\u5ba1\u6279\u7a0b\u5e8f\u83b7\u51c6\u4e0a\u5e02<\/span><\/span><\/strong>\u3002\u76ee\u524d\uff0c\u514b\u5511\u66ff\u5c3c\u5df2\u5728<\/span> 47 \u4e2a\u56fd\u5bb6\u548c\u5730\u533a\u83b7\u51c6\u4e0a\u5e02<\/span><\/span><\/p>\n

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2014\u5e74<\/span>9<\/span>\u6708<\/span>18<\/span>\u65e5\u83b7\u4e2d\u56fd\u98df\u54c1\u836f\u54c1\u76d1\u7763\u7ba1\u7406\u5c40\uff08<\/span>CFDA<\/span>\uff09\u6279\u51c6\u4e0a\u5e02<\/span><\/span>\u3002<\/span>2016\u5e74<\/span>3<\/span>\u6708\uff0c\u7f8e\u56fd<\/span>FDA<\/span>\u6279\u51c6\u514b\u5511\u66ff\u5c3c\u3001\u53ef\u7528\u4e8e\u6cbb\u7597\u643a\u5e26<\/span>ROS-1<\/span>\u57fa\u56e0\u7a81\u53d8\u7684\u665a\u671f\uff08\u8f6c\u79fb\u6027\uff09\u975e\u5c0f\u7ec6\u80de\u80ba\u764c\uff08<\/span>NSCLC<\/span>\uff09\u60a3\u8005\u3002\u81f3\u6b64\uff0c\u514b\u5511\u66ff\u5c3c\u6210\u4e3a\u76ee\u524d\u552f\u4e00\u4e00\u4e2a\u540c\u65f6\u83b7\u5f97<\/span>ALK<\/span>\u548c<\/span>ROS-1<\/span>\u4e24\u4e2a<\/span>NSCLC<\/span>\u6cbb\u7597\u6027\u9776\u70b9\u9002\u5e94\u75c7\u7684\u9776\u5411\u836f\u7269\u3002<\/span><\/span>\u53ef\u8fdb\u884c\u51c6\u786e\u7684\u80ba\u764c\u57fa\u56e0\u68c0\u6d4b\u3002\u53ef\u4ee5\u8bf4\u514b\u5511\u66ff\u5c3c\u7684\u51fa\u73b0\u5f00\u542f\u4e86\u975e\u5c0f\u7ec6\u80de\u80ba\u764c\u7cbe\u51c6\u6cbb\u7597\uff0c\u957f\u671f\u751f\u5b58\u7684\u65f6\u4ee3\u65b0\u7bc7\u7ae0\u3002<\/span><\/p>\n

 <\/span><\/p>\n

\u836f\u7269\u57fa\u672c\u4fe1\u606f<\/span><\/strong><\/span><\/p>\n

\"\u6df1\u5ea6\u9605\u8bfb\uff1a<\/p>\n


<\/span><\/strong><\/p>\n

\u4e34\u5e8a\u7597\u6548\uff1a<\/span><\/strong><\/p>\n

 <\/span><\/strong><\/p>\n

\u514b\u5511\u66ff\u5c3c\u662f<\/span>ALK\u3001<\/span>ROS<\/span>\u3001<\/span>MET<\/span>\u6291\u5236\u5242\uff0c\u5728\u4e00\u9879\u6b63\u5728\u8fdb\u884c<\/span>\u2160<\/span>\u671f\u4e34\u5e8a\u7814\u7a76<\/span>ROS1<\/span>\u9633\u6027\u665a\u671f<\/span>NSCLC<\/span>\u60a3\u8005\u6269\u5c55\u961f\u5217\u4e2d\u663e\u793a\u663e\u8457\u6297\u80bf\u7624\u6d3b\u6027\u3002\u8be5\u5f00\u653e\u6027\u5355\u81c2<\/span>\u2161<\/span>\u671f\u7814\u7a76\u8bc4\u4f30\u4e86\u514b\u5511\u66ff\u5c3c\u5728\u8fc4\u4eca\u6700\u5927\u6837\u672c<\/span>ROS1<\/span>\u9633\u6027\u665a\u671f<\/span>NSCLC<\/span>\u60a3\u8005\u4e2d\u7684\u7597\u6548\u548c\u5b89\u5168\u6027\u3002<\/span><\/span><\/p>\n

 <\/span><\/strong><\/p>\n

\u56fd\u5185\u7533\u62a5\u60c5\u51b5\uff1a<\/span><\/strong><\/p>\n

 <\/span><\/strong><\/p>\n

\u7531\u4e8e\u514b\u5511\u66ff\u5c3c\u5c1a\u5728\u4e13\u5229\u4fdd\u62a4\u671f\u5185\uff0c\u56e0\u6b64\u56fd\u5185\u4eff\u5236\u8f83\u5c11\u3002\u76ee\u524d\u4ec5\u6b63\u5927\u5929\u6674\u4e00\u5bb6\u4f01\u4e1a\u5728\u7533\u62a5\u3002<\/span><\/p>\n

 <\/span><\/p>\n

\u5408\u6210\u8def\u7ebf<\/span><\/strong><\/span><\/p>\n

 <\/span><\/strong><\/span><\/p>\n

2016\u5e74<\/span>8\u6708\u51ef\u83b1\u82f1\u533b\u836f\u96c6\u56e2\u62ab\u9732\u4e86\u6539\u8fdb\u7684<\/span> Crizotinib \u5408\u6210\u8def\u7ebf\uff08\u4e13\u5229\u53f7<\/span> CN 105906656\uff09\uff0c\u5982\u6240\u793a\uff0c\u5c06\u5316\u5408\u7269\uff08<\/span>28\uff09\u7684\u539f\u5408\u6210\u8def\u7ebf\uff08\u56fe\u4e00<\/span>\uff0c\u7531\u8f89\u745e\u516c\u53f8\u53d1\u660e\uff09\u6539\u7528\u4e24\u6b65\u8fde\u7eed\u6d41\u53cd\u5e94\u6765\u5b9e\u73b0\u3002<\/span><\/span><\/p>\n

\u56fe\u4e00\uff1a<\/span><\/p>\n

\"\u6df1\u5ea6\u9605\u8bfb\uff1a<\/p>\n

\"\u6df1\u5ea6\u9605\u8bfb\uff1a<\/p>\n


<\/p>\n

\n
\u5df2\u4e0a\u5e02\u4e8c\u4ee3 ALK\u6291\u5236\u5242<\/span><\/section>\n
<\/section>\n
<\/section>\n<\/section>\n


<\/p>\n

1 <\/span>\u8272\u745e\u66ff\u5c3c\uff08<\/span>Ceritinib\uff1b<\/span>LDKLDK378<\/span>\uff09<\/span><\/span><\/strong><\/p>\n


<\/p>\n

\"\u6df1\u5ea6\u9605\u8bfb\uff1a<\/p>\n


<\/p>\n

\u8272\u745e\u66ff\u5c3c\uff08<\/span>LDK378\uff09\u662f\u7531\u8bfa\u534e\u5236\u836f\u7814\u53d1\u7684\u4e00\u79cd\u65b0\u578b\u7684<\/span>ALK<\/span>\u6291\u5236\u5242\uff0c\u5c5e\u4e8e\u7b2c\u4e8c\u4ee3<\/span>ALK<\/span>\u6291\u5236\u5242\u3002\u4e0e\u7b2c\u4e00\u4ee3<\/span>ALK<\/span>\u6291\u5236\u5242<\/span><\/span>\u514b\u5511\u66ff\u5c3c\uff08<\/span>crizotinib<\/span>\uff09\u76f8\u6bd4\uff0c<\/span>Zykadia\u00ae<\/span><\/sup>\u80fd\u591f\u514b\u670d<\/span><\/span>\u514b\u5511\u66ff\u5c3c<\/span>\u51fa\u73b0\u7684\u6297\u836f\u6027\u5373<\/span>ALK\u7684\u8010\u836f\u7a81\u53d8\u7684\u95ee\u9898\u3002\u56e0\u6b64<\/span>2014\u5e74<\/span>4<\/span>\u6708<\/span>29<\/span>\u65e5\u83b7<\/span>FDA<\/span>\u6279\u51c6\u4e0a\u5e02<\/span><\/strong>\uff0c\u5e76\u4e14\u6388\u4e88<\/span>Zykadia\u7a81\u7834\u6027\u6cbb\u7597\u836f\u7269\u8d44\u683c\uff0c\u4f18\u5148\u5ba1\u8bc4\u53ca\u5b64\u513f\u836f\u8d44\u683c\uff0c\u56e0\u4e3a\u8fd9\u6b3e\u836f\u7269\u7684\u7533\u8bf7\u8005\u901a\u8fc7\u521d\u6b65\u4e34\u5e8a\u8bd5\u9a8c\u8bc1\u636e\u8bc1\u660e\u8fd9\u6b3e\u836f\u7269\u53ef\u80fd\u4f1a\u63d0\u4f9b\u4e00\u79cd\u76f8\u5bf9\u73b0\u6709\u6cbb\u7597\u836f\u7269\u7684\u5b9e\u8d28\u6027\u6539\u5584\uff1b\u8fd9\u6b3e\u836f\u7269\u5728\u5176\u7533\u8bf7\u63d0\u4ea4\u65f6\uff0c\u5728\u4e00\u79cd\u4e25\u91cd\u75be\u75c5\u6cbb\u7597\u7684\u5b89\u5168\u6027\u6216\u6709\u6548\u6027\u65b9\u9762\u53ef\u80fd\u6709\u663e\u8457\u6539\u5584\uff0c\u5e76\u4e14\u8fd9\u6b3e\u836f\u7269\u65e8\u5728\u6cbb\u7597\u4e00\u79cd\u7f55\u89c1\u75be\u75c5\u3002<\/span><\/span><\/p>\n

 <\/span><\/p>\n

2015\u5e74<\/span>5<\/span>\u6708<\/span>11<\/span>\u65e5\uff0c\u8bfa\u534e\u9488\u5bf9\u95f4\u53d8\u6027\u6dcb\u5df4\u7624\u6fc0\u9176\u9633\u6027\uff08<\/span>ALK+<\/span>\uff09\u8f6c\u79fb\u6027\u975e\u5c0f\u7ec6\u80de\u80ba\u764c\uff08<\/span>NSCLC<\/span>\uff09\u60a3\u8005\u7684\u6cbb\u7597\u836f\u7269<\/span>Zykadia<\/span>\u83b7\u5f97\u4e86\u6b27\u6d32\u836f\u54c1\u7ba1\u7406\u5c40\u7684\u6279\u51c6\uff0c\u7528\u4e8e\u6cbb\u7597\u95f4\u53d8\u6027\u6dcb\u5df4\u7624\u6fc0\u9176\u9633\u6027\uff08<\/span>ALK+<\/span>\uff09\u8f6c\u79fb\u6027\u975e\u5c0f\u7ec6\u80de\u80ba\u764c\uff08<\/span>NSCLC<\/span>\uff09\uff0c\u8fd9\u7c7b\u60a3\u8005\u75c5\u60c5\u5df2\u7ecf\u6076\u5316\u6216\u5bf9\u8f89\u745e\u7684<\/span>Xalkori (crizotinib)<\/span>\u4e0d\u8010\u53d7\u3002\u9488\u5bf9\u8fd9\u90e8\u5206\u60a3\u8005\uff0c<\/span>Zykadia<\/span><\/span><\/p>\n

(ceritinib)\u5c06\u6210\u4e3a\u9996\u9009\u6cbb\u7597\u836f\u7269\u3002\u8fd9\u9879\u6279\u51c6\u51b3\u5b9a\u4e3b\u8981\u662f\u57fa\u4e8e\u4e24\u4e2a\u5168\u7403\u6027\u3001\u591a\u4e2d\u5fc3\u3001\u975e\u76f2\u5355\u7ec4\u4e34\u5e8a\u5b9e\u9a8c\u7ed3\u679c\u3002\u7b2c\u4e00\u4e2a\u540d\u4e3a<\/span>ASCEND-1<\/span>\u7684\u8bd5\u9a8c<\/span>A<\/span>\u7ed3\u679c\u663e\u793a\uff0c\u7ed9\u836f\u7684\u60a3\u8005\u6574\u4f53\u53cd\u5e94\u7387\uff08\u80bf\u7624\u7f29\u5c0f\uff09\u4e3a<\/span>56.4%<\/span>\u3002\u800c\u8bd5\u9a8c<\/span>B<\/span>\uff08<\/span>ASCEND-2<\/span>\uff09\u7684\u6570\u636e\u5c06\u4f1a\u5728\u5373\u5c06\u5230\u6765\u7684\u4e00\u4e2a\u533b\u5b66\u4f1a\u8bae\u4e0a\u516c\u5e03\u3002<\/span><\/span><\/p>\n

 <\/span><\/p>\n

2017\u5e74<\/span>5<\/span>\u6708<\/span>26<\/span>\u65e5\uff0c\u8bfa\u534e\u5236\u836f\u8868\u793a\uff0c\u7f8e\u56fd<\/span>FDA\u6279\u51c6\u4e86<\/span>Zykadia\u00ae (Ceritinib<\/span>\uff0c\u8272\u745e\u66ff\u5c3c<\/span>)<\/span>\u7684\u65b0\u7684\u9002\u5e94\u75c7\u7533\u8bf7\uff0c\u7528\u4e8e<\/span>ALK<\/span>\u9633\u6027\u7684\u8f6c\u79fb\u6027\u975e\u5c0f\u7ec6\u80de\u80ba\u764c\uff08<\/span>NSCLC<\/span>\uff09\u60a3\u8005\u7684\u4e00\u7ebf\u6cbb\u7597\u3002<\/span><\/span><\/p>\n

 <\/span><\/p>\n

\u836f\u7269\u4fe1\u606f<\/span><\/strong><\/span><\/p>\n

\"\u6df1\u5ea6\u9605\u8bfb\uff1a<\/p>\n


<\/p>\n

\u4e34\u5e8a\u7597\u6548\uff1a<\/span><\/strong><\/p>\n

 <\/span><\/strong><\/p>\n

\u8272\u745e\u66ff\u5c3c\u662f\u4e00\u79cd\u53e3\u670d\u7684<\/span>TKI ALK\u6291\u5236\u5242\uff0c\u5df2\u88ab<\/span>FDA<\/span>\u6279\u51c6\u7528\u4e8e\u514b\u5511\u66ff\u5c3c\u8fdb\u5c55\u6216\u4e0d\u80fd\u8010\u53d7\u3001<\/span>ALK<\/span>\u9633\u6027\u7684\u8f6c\u79fb\u6027\u975e\u5c0f\u7ec6\u80de<\/span><\/span>\u80ba\u764c<\/span>\u60a3\u8005\u3002\u6279\u51c6\u662f\u6839\u636e\u4e00\u9879\u6269\u5c55\u7684<\/span>1\u671f\u7814\u7a76\uff08<\/span>ASCEND-1<\/span>\uff09\u663e\u793a\uff0c\u5728\u65e2\u5f80\u5df2\u63a5\u53d7\u514b\u5511\u66ff\u5c3c\u6cbb\u7597\u7684\u60a3\u8005\u4e2d\uff0c\u8272\u745e\u66ff\u5c3c\u6cbb\u7597\u7684\u603b\u6709\u6548\u7387\u4e3a<\/span>56%<\/span>\uff08<\/span>92\/163<\/span>\uff09\uff1b\u4e2d\u4f4d\u7597\u6548\u6301\u7eed\u65f6\u95f4\u662f<\/span>8.3<\/span>\u4e2a\u6708\uff08<\/span>6.8-9.7<\/span>\uff09\u3002\u5e38\u89c1\u7684<\/span>3-4<\/span>\u7ea7\u4e0d\u826f\u4e8b\u4ef6\u5305\u62ec\u4e19\u6c28\u9178\u6c28\u57fa\u8f6c\u79fb\u9176\u5347\u9ad8\uff08<\/span>73<\/span>\u4f8b<\/span>[30%]<\/span>\uff09\u53ca\u5929\u51ac\u6c28\u9178\u8f6c\u6c28\u9176\u5347\u9ad8\uff08<\/span>25<\/span>\u4f8b<\/span>[10%]<\/span>\uff09\u3002\u67d0\u4e9b\u5177\u6709<\/span>CNS<\/span>\u75c5\u53d8\u7684\u60a3\u8005\u5bf9\u8272\u745e\u66ff\u5c3c\u5e94\u7b54\u3002\u57fa\u4e8e\u8be5\u7814\u7a76\u548c<\/span>FDA<\/span>\u7684\u6279\u51c6\uff0c\u7814\u7a76\u5c0f\u7ec4\u5efa\u8bae\u8272\u745e\u66ff\u5c3c\u4f5c\u4e3a<\/span>ALK<\/span>\u9633\u6027\u7684<\/span>NSCLC<\/span>\u60a3\u8005\u5728\u514b\u5511\u66ff\u5c3c\u8fdb\u5c55\u540e\u7684\u540e\u7eed\u6cbb\u7597\u3002\u4e0d\u8010\u53d7\u514b\u5511\u66ff\u5c3c\u7684\u60a3\u8005\u53ef\u4ee5\u8f6c\u6362\u81f3\u963f\u96f7\u66ff\u5c3c\u6216\u8272\u745e\u66ff\u5c3c\uff08\u5982\u679c\u65e2\u5f80\u672a\u7ed9\u4e88\uff09\u6216\u5e03\u52a0\u66ff\u5c3c\u3002\u4e00\u9879<\/span>2<\/span>\u671f\u8bd5\u9a8c\uff08<\/span>ASCEND-2<\/span>\uff09\u8bc4\u4f30\u4e86\u8272\u745e\u66ff\u5c3c\u6cbb\u7597\u65e2\u5f80\u66fe\u63a5\u53d7\u8fc7\u81f3\u5c11<\/span>2<\/span>\u4e2a\u6216\u4ee5\u4e0a\u6cbb\u7597\u3001\u514b\u5511\u66ff\u5c3c\u8fdb\u5c55\u5e76\u6709\u8111\u8f6c\u79fb\u7684\u60a3\u8005\u3002\u603b\u6709\u6548\u7387\u662f<\/span>38%<\/span>\uff1b\u7597\u6548\u6301\u7eed\u65f6\u95f4\u662f<\/span>9.7<\/span>\u4e2a\u6708\uff08<\/span>95%CI<\/span>\uff0c<\/span>7.1-11.1<\/span>\u4e2a\u6708\uff09\u3002\u9885\u5185\u75c5\u53d8\u603b\u6709\u6548\u7387\u4e3a<\/span>45.0%<\/span>\uff08<\/span>95%CI<\/span>\uff0c<\/span>23.1%-68.5%<\/span>\uff09\u3002<\/span><\/span><\/p>\n

 <\/span><\/p>\n

\u6839\u636e\u8be5<\/span>3\u671f\u8bd5\u9a8c\uff0c<\/span>2017<\/span>\u7b2c<\/span>5<\/span>\u7248\u66f4\u65b0\uff0c<\/span>NCCN<\/span>\u5c0f\u7ec4\u63a8\u8350\uff08<\/span>1<\/span>\u7c7b\uff09\u8272\u745e\u66ff\u5c3c\u4f5c\u4e3a<\/span>ALK<\/span>\u9633\u6027\u8f6c\u79fb\u6027\u975e\u5c0f\u7ec6\u80de<\/span><\/span>\u80ba\u764c<\/span>\u60a3\u8005\u7684\u4e00\u7ebf\u6cbb\u7597\u3002<\/span>2017\u7b2c<\/span>7<\/span>\u7248\u66f4\u65b0\uff0c\u4e13\u5bb6\u7ec4\u6210\u5458\u6295\u7968\u51b3\u5b9a\u963f\u96f7\u66ff\u5c3c\u662f<\/span>ALK<\/span>\u57fa\u56e0\u91cd\u6392\u9633\u6027\u7684\u8f6c\u79fb\u6027\u975e\u5c0f\u7ec6\u80de<\/span><\/span>\u80ba\u764c<\/span>\u60a3\u8005\u4e00\u7ebf\u6cbb\u7597\u9996\u9009\u836f\u7269\u3002<\/span><\/p>\n

 <\/span><\/h1>\n

\u503c\u5f97\u6ce8\u610f\u7684\u662f\uff0c\u7ec6\u80de\u6c34\u5e73\u7684\u7814\u7a76\u8868\u660e\uff0c\u8272\u745e\u66ff\u5c3c\u5bf9\u514b\u5511\u66ff\u5c3c\u8010\u836f\u6027\u7ec6\u80de\u6709\u660e\u663e\u7684\u6291\u5236\u4f5c\u7528\uff0c\u5176\u5bf9\u8010\u836f\u7a81\u53d8<\/span>L1196M\u3001<\/span>G1269A<\/span>\u3001<\/span>I1171T<\/span>\u548c<\/span>S1206Y<\/span>\u6291\u5236\u4f5c\u7528\u660e\u663e\uff0c\u4f46\u5bf9<\/span>G1202R<\/span>\u548c<\/span>F1174C<\/span>\u7a81\u53d8\u65e0\u6548\u3002<\/span><\/span><\/h1>\n

 <\/span><\/p>\n

\u56fd\u5185\u7533\u62a5\u60c5\u51b5<\/span><\/strong><\/p>\n

 <\/span><\/strong><\/p>\n

\u65e9\u5728<\/span>2013\u5e74\uff0c\u539f\u7814\u4f01\u4e1a\u5317\u4eac\u8bfa\u534e\u5c31\u5df2\u5411<\/span>CFDA<\/span>\u63d0\u51fa\u8272\u745e\u66ff\u5c3c\u80f6\u56ca\u7684\u8fdb\u53e3\u6ce8\u518c\uff0c\u4e14\u4e8e\u540c\u5e74\u83b7\u5f97\u4e34\u5e8a\u6279\u4ef6\u8fdb\u884c\u4e34\u5e8a\u7814\u7a76\uff0c\u76ee\u524d\u5904\u4e8e\u9a8c\u8bc1\u6027\u4e34\u5e8a\u8bd5\u9a8c\u9636\u6bb5\u3002\u8fc4\u4eca\uff0c\u56fd\u5185\u5df2\u6709\u591a\u5bb6\u4f01\u4e1a\u5411<\/span>CFDA<\/span>\u63d0\u51fa\u6709\u5173\u672c\u54c1\u539f\u6599\u836f\u548c\u5236\u5242\u7684\u4e34\u5e8a\u6ce8\u518c\u7533\u8bf7\uff0c\u8be6\u89c1\u4e0b\u8868\u3002\u5176\u4e2d\uff0c\u77f3\u836f\u96c6\u56e2\u4e2d\u5947\u5236\u836f\u6280\u672f\uff08\u77f3\u5bb6\u5e84\uff09\u6709\u9650\u516c\u53f8\u5f00\u53d1\u7684\u539f\u6599\u836f\u548c\u80f6\u56ca\u5df2\u7387\u5148\u83b7\u5f97\u4e34\u5e8a\u6279\u4ef6\u3002\u7136\u540e\uff0c\u5f90\u5dde\u4e07\u90a6\u3001\u6c5f\u82cf\u5965\u8d5b\u5eb7\u3001\u5317\u4eac\u5eb7\u7acb\u548c\u5148\u58f0\u5236\u836f\u5747\u6279\u5b8c\u6bd5\u3002<\/span><\/span><\/p>\n

 <\/span><\/p>\n

\u5408\u6210\u8def\u7ebf<\/span><\/strong><\/p>\n

 <\/span><\/strong><\/p>\n

\u8272\u745e\u66ff\u5c3c\u7684\u5408\u6210\u7528\u6c47\u805a\u6cd5\uff0c\u5148\u5408\u6210\u4e24\u4e2a\u5206\u5b50\u91cf\u63a5\u8fd1\u7684\u7247\u6bb5\uff0c\u7136\u540e\u5c06\u4e24\u4e2a\u7247\u6bb5\u62fc\u63a5\u800c\u6210\u3002\u7b2c\u4e00\u4e2a\u7247\u6bb5\u4ece\u5316\u5408\u7269<\/span>1\u5f00\u59cb\uff0c\u785d\u5316\u540e\u7528\u5f02\u4e19\u9187\u7ecf<\/span>SNAr<\/span>\u53cd\u5e94\u5f97\u5230<\/span>2,2<\/span>\u548c<\/span>3<\/span>\u7ecf<\/span>Suzuki<\/span>\u5076\u8054\u540e<\/span>PtO2<\/span>\u50ac\u5316\u6c22\u5316\u8fd8\u539f\u785d\u57fa\u540e\u6210\u76d0\u5f97\u5230\u7247\u6bb5<\/span>4<\/span>\u3002\u53e6\u5916\u4e00\u4e2a\u7247\u6bb5\u4ece\u5316\u5408\u7269<\/span>5<\/span>\u5f00\u59cb\u7528\u5f02\u4e19\u786b\u9187\u540c\u6837\u7ecf<\/span>SNAr<\/span>\u53cd\u5e94\uff0c\u518d\u6c27\u5316\u786b\u919a\u5230\u781c\uff0c\u540e\u8fd8\u539f\u785d\u57fa\u5f97\u5230<\/span>6,6<\/span>\u4e0e<\/span>7<\/span>\u7ecf<\/span>SNAr<\/span>\u53cd\u5e94\u5f97\u5230<\/span>8<\/span>\u3002\u8fd9\u91cc\u987a\u4fbf\u63d0\u4e00\u53e5\uff0c<\/span>7<\/span>\u4e2d\u6709\u4e09\u4e2a\u6c2f\uff0c\u5982\u679c\u662f<\/span>SNAr<\/span>\u53cd\u5e94\u7684\u8bdd\uff0c\u8bba\u53cd\u5e94\u6d3b\u6027<\/span>4<\/span>\u4f4d\u6c2f\u5927\u4e8e<\/span>2<\/span>\u4f4d\u6c2f\u8fdc\u8fdc\u5927\u4e8e<\/span>5<\/span>\u4f4d\u6c2f\uff0c\u8fd9\u662f\u7531<\/span>SNAr<\/span>\u53cd\u5e94\u90bb\uff0c\u5bf9\u4f4d\u9700\u8981\u5438\u7535\u5b50\u57fa\u56e2\u51b3\u5b9a\u7684\u3002\u5316\u5408\u7269<\/span>8<\/span>\u5c31\u662f\u7b2c\u4e8c\u4e2a\u7247\u6bb5\uff0c\u4e0e\u5316\u5408\u7269<\/span>4<\/span>\u518d\u7ecf<\/span>SNAr<\/span>\u53cd\u5e94\u540e\u7ecf\u8fc7\u78b1\u6027\u4e2d\u548c\u5f97\u5230\u8272\u745e\u66ff\u5c3c\u3002<\/span>8<\/span>\u548c<\/span>4<\/span>\u7684<\/span>SNAr<\/span>\u53cd\u5e94\u8bbe\u8ba1\u5f88\u6709\u6280\u5de7\uff0c\u901a\u5e38\u60c5\u51b5\u4e8c\u7ea7\u8102\u80aa\u80fa\u7684\u4eb2\u6838\u6027\u5927\u4e8e\u82ef\u80fa\uff0c\u5728\u5316\u5408\u7269<\/span>4<\/span>\u4e2d\uff0c\u4e8c\u7ea7\u80fa\u53d8\u6210\u76d0\u9178\u76d0\uff0c\u4ece\u800c\u5927\u5927\u964d\u4f4e\u5176\u6d3b\u6027\uff0c\u6240\u4ee5\u548c<\/span>8<\/span>\u53cd\u5e94\u65f6\uff0c\u662f\u82ef\u80fa\u53cd\u5e94\uff0c\u800c\u4e0d\u662f\u4e8c\u7ea7\u8102\u80aa\u80fa\u3002<\/span><\/span><\/p>\n


<\/p>\n

\"\u6df1\u5ea6\u9605\u8bfb\uff1a<\/p>\n


<\/p>\n

2. <\/span>\u827e\u4e50\u66ff\u5c3c\uff08<\/span>AlectinibCHH5424802\/RO5424802\uff09<\/span><\/span><\/strong><\/p>\n


<\/p>\n

\"\u6df1\u5ea6\u9605\u8bfb\uff1a<\/p>\n


<\/p>\n

\u827e\u4e50\u66ff\u5c3c\uff08<\/span>Alcetinib\uff09\u662f\u7531\u7f57\u6c0f\u516c\u53f8<\/span>(Roche)<\/span>\u7684\u5206\u516c\u53f8\u65e5\u672c\u4e2d\u5916\u5236\u836f\u73e0\u5f0f\u4f1a\u793e<\/span>(Chugan Pharmacettical)<\/span>\u5f00\u53d1\u7684\u4e00\u79cd\u65b0\u95f4\u53d8\u6027\u6dcb\u5df4\u7624\u6fc0\u9176<\/span>(ALK)<\/span>\u7684\u6291\u5236\u5242\u3002<\/span><\/span>\u662f\u7ee7\u514b\u5511\u66ff\u5c3c\uff08<\/span>crizotinib\uff09\u548c\u8272\u745e\u66ff\u5c3c\uff08<\/span>ceritinib<\/span>\uff09\u540e\u7f8e\u56fd\u98df\u54c1\u548c\u836f\u7269\u7ba1\u7406\u5c40\uff08<\/span>FDA<\/span>\uff09\u6279\u51c6\u7684\u7b2c<\/span>3<\/span>\u4e2a\u7528\u4e8e\u6cbb\u7597<\/span>ALK <\/span>\u9633\u6027\u7684<\/span>NSCLC <\/span>\u7684\u836f\u7269\u3002\u827e\u4e50\u66ff\u5c3c\u7684\u4f18\u52bf\u5728\u4e8e\u4e0d\u4ec5\u5bf9\u7ecf\u514b\u5511\u66ff\u5c3c\u6cbb\u7597\u540e\u75be\u75c5\u8fdb\u5c55\u6216\u8010\u836f\u7684\u665a\u671f\uff08\u8f6c\u79fb\u6027\uff09<\/span>ALK <\/span>\u9633\u6027\u7684<\/span>NSCLC<\/span>\u6709\u6548\uff0c\u8fd8\u53ef\u4f7f\u8111\u8f6c\u79fb\u60a3\u8005\u7684\u8111\u80bf\u7624\u7f29\u5c0f\uff0c\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\u5177\u6709\u5f88\u597d\u7684\u5b89\u5168\u6027\u53ca\u8010\u53d7\u6027\u3002\u76ee\u524d\u7f57\u6c0f\u516c\u53f8\u5df2\u5411\u56fd\u5bb6\u98df\u54c1\u836f\u54c1\u76d1\u7763\u7ba1\u7406\u603b\u5c40\uff08<\/span>CFDA<\/span>\uff09\u7533\u8bf7\u8fdb\u53e3\u6ce8\u518c\uff0c\u5e76\u5df2\u83b7\u5f97\u4e34\u5e8a\u6279\u6587\uff0c\u5e76\u4e8e<\/span><\/span>2015\u5e74<\/span>12<\/span>\u6708<\/span>11<\/span>\u65e5\u5728\u7f8e\u56fd\u4e0a\u5e02\uff0c\u5546\u54c1\u540d <\/span>Alecensa<\/span><\/span><\/strong>\u3002\u827e\u4e50\u66ff\u5c3c\u5c5e\u4e8e\u7b2c<\/span>2\u4ee3\u95f4\u53d8\u6027\u6dcb\u5df4\u7624\u6fc0\u9176<\/span>( anaplastic lymphomakinase<\/span>\uff0c<\/span>ALk) <\/span>\u6291\u5236\u5242\uff0c\u7528\u4e8e\u6cbb\u7597<\/span>ALK <\/span>\u57fa\u56e0\u7a81\u53d8\u7684\u665a\u671f\u975e\u5c0f\u7ec6\u80de\u80ba\u764c\u60a3\u8005\u3002<\/span><\/span><\/p>\n

 <\/span><\/p>\n

2017\u5e74<\/span>11<\/span>\u6708<\/span>7<\/span>\u65e5\uff0c<\/span>FDA\u6279\u51c6\u827e\u4e50\u66ff\u5c3c\u7528\u4e8e\u4e00\u7ebf\u6cbb\u7597\u95f4\u53d8\u6027\u6dcb\u5df4\u7624\u6fc0\u9176\uff08<\/span>ALK<\/span>\uff09\u7a81\u53d8\u9633\u6027\u7684\u975e\u5c0f\u7ec6\u80de\u80ba\u764c\uff08<\/span>NSCLC<\/span>\uff09\u60a3\u8005\u3002<\/span><\/span><\/p>\n

 <\/span><\/p>\n

\u76ee\u524d\u8be5\u836f\u5728\u4e2d\u56fd\u5904\u4e8e\u4e09\u671f\u4e34\u5e8a\u9636\u6bb5\uff0c\u8bd5\u9a8c\u767b\u8bb0\u65f6\u95f4\u4e3a<\/span>2015\u5e74<\/span>10<\/span>\u6708<\/span>26<\/span>\u65e5\uff0c\u5982\u679c\u4e00\u5207\u987a\u5229\u7684\u8bdd\uff0c\u9884\u8ba1<\/span>2018<\/span>\u5e74\u5728\u56fd\u5185\u4e0a\u5e02\u3002<\/span><\/span><\/p>\n

 <\/span><\/p>\n

\u836f\u7269\u4fe1\u606f<\/span><\/strong><\/p>\n


<\/p>\n

\"\u6df1\u5ea6\u9605\u8bfb\uff1a<\/p>\n


<\/p>\n

\u4e34\u5e8a\u7597\u6548<\/span><\/strong><\/p>\n

 <\/span><\/strong><\/p>\n

\u4e24\u9879\u5355\u81c2\u4e34\u5e8a\u8bd5\u9a8c\u8bc1\u5b9e\u4e86<\/span>Alecensa\u7684\u5b89\u5168\u6027\u4e0e\u6709\u6548\u6027\u3002\u8fd9\u4e24\u9879\u4e34\u5e8a\u8bd5\u9a8c\u7684\u53d7\u8bd5\u8005\u90fd\u662f\u4e0d\u518d\u5bf9\u514b\u5511\u66ff\u5c3c\u6cbb\u7597\u654f\u611f\u7684\u8f6c\u79fb\u6027<\/span>ALK<\/span>\u9633\u6027<\/span>NSCLC<\/span>\u60a3\u8005\uff0c\u4ed6\u4eec\u63a5\u53d7\u4e86\u4e00\u5929\u4e24\u6b21\u7684\u53e3\u670d<\/span>Alecensa<\/span>\u6cbb\u7597\u3002\u7b2c\u4e00\u9879\u4e34\u5e8a\u8bd5\u9a8c\u6709<\/span>38%<\/span>\u7684\u60a3\u8005\u8fbe\u5230\u4e86<\/span>NSCLC<\/span>\u80bf\u7624\u90e8\u5206\u7f29\u5c0f\uff0c\u4e14\u7597\u6548\u5e73\u5747\u6301\u7eed\u4e86<\/span>7.5<\/span>\u4e2a\u6708\u3002\u7b2c\u4e8c\u9879\u4e34\u5e8a\u8bd5\u9a8c\u6709<\/span>44%<\/span>\u7684\u60a3\u8005\u8fbe\u5230\u4e86<\/span>NSCLC<\/span>\u80bf\u7624\u90e8\u5206\u7f29\u5c0f\uff0c\u4e14\u7597\u6548\u5e73\u5747\u6301\u7eed\u4e86<\/span>11.2<\/span>\u4e2a\u6708\u3002\u8fd9\u4e24\u9879\u4e34\u5e8a\u8bd5\u9a8c\u8fd8\u8bc4\u4f30\u4e86<\/span>Alecensa<\/span>\u5bf9\u60a3\u8005\u7684\u8111\u5185\u8f6c\u79fb\u7624\u7684\u7597\u6548\u3002\u5728\u5177\u6709\u53ef\u6d4b\u91cf\u7684\u8111\u5185\u8f6c\u79fb\u7624\u7684\u53d7\u8bd5\u8005\u4e2d\uff0c\u6709<\/span>61%<\/span>\u7684\u53d7\u8bd5\u8005\u8fbe\u5230\u4e86\u8111\u5185\u8f6c\u79fb\u7624\u5b8c\u5168\u6d88\u5931\u6216\u90e8\u5206\u7f29\u5c0f\uff0c\u4e14\u7597\u6548\u5e73\u5747\u6301\u7eed\u4e86<\/span>9.1<\/span>\u4e2a\u6708\u3002<\/span><\/span><\/p>\n

 <\/span><\/p>\n

\u503c\u5f97\u6ce8\u610f\u7684\u662f\uff0c\u8be5\u9879\u7814\u7a76\u53d1\u73b0\u9488\u5bf9\u6709\u660e\u786e\u8111\u90e8\u75c5\u7076\u7684\u60a3\u8005\uff0c\u827e\u4e50\u66ff\u5c3c\u7684\u6709\u6548\u7387<\/span>81%\uff0c\u514b\u5511\u66ff\u5c3c\u7ec4\u7684\u6709\u6548\u7387\u53ea\u6709<\/span>50%<\/span>\u3002\u7528\u836f\u4e00\u5e74\u4e4b\u540e\uff0c\u827e\u4e50\u66ff\u5c3c\u7ec4\u7684\u8111\u90e8\u8fdb\u5c55\u6bd4\u4f8b\u53ea\u6709<\/span>9.4%<\/span>\uff0c\u800c\u514b\u5511\u66ff\u5c3c\u7ec4\u9ad8\u8fbe<\/span>41.4%<\/span>\u3002<\/span><\/span><\/p>\n

 <\/span><\/p>\n

\u5408\u6210\u8def\u7ebf<\/span><\/strong><\/p>\n

 <\/span><\/strong><\/p>\n

\u4ece\u5316\u5408\u7269<\/span>S-1\u51fa\u53d1\uff0c\u7ecf\u8fc7\u6eb4\u4ee3\u53cd\u5e94\u5f97\u5230\u5316\u5408\u7269<\/span>S-2<\/span>\uff0c\u968f\u540e\u548c\u82ef\u80bc<\/span>S-3<\/span>\u901a\u8fc7<\/span>Fischer<\/span>\u5432\u54da\u5408\u6210\u6cd5\u5f97\u5230\u56db\u73af\u5316\u5408\u7269<\/span>S-4<\/span>\u3002\u968f\u540e<\/span>DDQ<\/span>\u6c27\u5316\u5f97\u5230\u82b3\u9999\u916e\u5316\u5408\u7269<\/span>S-5<\/span>\u3002<\/span>S-5<\/span>\u5728\u5421\u5576\u76d0\u9178\u76d0\u9ad8\u6e29\u53cd\u5e94\uff0c\u8131\u9664\u82b3\u73af\u4e0a\u7532\u57fa\u919a\u4fdd\u62a4\uff0c\u968f\u540e<\/span>Tf<\/span>\u4fdd\u62a4\u915a\u7f9f\u57fa\uff0c\u518d\u548c<\/span>S-8<\/span>\u7ecf\u8fc7\u4eb2\u6838\u82b3\u9999\u53d6\u4ee3\u53cd\u5e94\u5f97\u5230\u5316\u5408\u7269<\/span>S-9<\/span>\u3002\u5f97\u5230<\/span>S-9<\/span>\u4ee5\u540e\uff0c\u5728<\/span>Pd<\/span>\u50ac\u5316\u4e0b\u548c\u7094\u70c3\u7ecf\u8fc7<\/span>Sonogashira<\/span>\u5076\u8054\u53cd\u5e94\u5f97\u5230\u7094\u70c3\u5316\u5408\u7269\uff0c<\/span>TBAF<\/span>\u8131\u9664\u7845\u57fa\u4fdd\u62a4\u5f97\u5230<\/span>S-10<\/span>\uff0c\u6700\u540e\u6c22\u5316\u8fd8\u539f\u7094\u57fa\u5f97\u5230<\/span>Alecensa(Alectinib<\/span>\uff0c\u827e\u4e50\u66ff\u5c3c<\/span>)<\/span>\u3002<\/span><\/span><\/p>\n


<\/p>\n

\"\u6df1\u5ea6\u9605\u8bfb\uff1a<\/p>\n

\u5408\u6210\u8def\u7ebf\u53c2\u8003<\/span>J. Med. Chem. 2011, 54, 6286.  &  WO2012023597<\/span><\/p>\n

 <\/span><\/p>\n

3 <\/span><\/strong>\u5e03\u5409\u4ed6\u6ee8\uff08<\/span>Brigatinib\uff0c<\/span>AP26113<\/span>\uff09<\/span><\/span><\/strong><\/p>\n


<\/p>\n

\"\u6df1\u5ea6\u9605\u8bfb\uff1a<\/p>\n


<\/p>\n

\u5e03\u5409\u4ed6\u6ee8<\/span>Brigatinib\u4f5c\u4e3a\u4e00\u6b3e<\/span>ALK<\/span>\u7684\u5f3a\u6548\u6291\u5236\u5242\uff0c\u5728<\/span><\/span>2017\u5e74<\/span>4<\/span>\u6708<\/span>28<\/span>\u65e5\uff0c\u7f8e\u56fd<\/span>FDA<\/span>\u52a0\u901f\u6279\u51c6\u4e0a\u5e02<\/span><\/span><\/strong>\uff0c\u7528\u4e8e\u6cbb\u7597\u7528\u4e8e\u6076\u5511\u70f7\u6cbb\u7597\u540e\u7684\u8fdb\u5c55<\/span>Creutinib\u4e0d\u80fd\u8010\u53d7<\/span>ALK<\/span>\u9633\u6027\u7684\u5c40\u90e8\u665a\u671f\u6216\u9759\u6001\u975e\u5c0f\u7ec6\u80de\u80ba\u764c\u3002\u5e03\u5409\u4ed6\u6ee8<\/span>Brigatinib<\/span>\u80fd\u6291\u5236<\/span>ALK<\/span>\u4ee5\u53ca<\/span>ALK<\/span>\u878d\u5408\u86cb\u767d\uff0c\u4ece\u800c\u6291\u5236\u80bf\u7624\u7684\u751f\u957f\uff0c\u5728\u4f53\u5916\u4e0e\u4f53\u5185\u8bd5\u9a8c\u4e2d\uff0c<\/span>brigatinib\u90fd\u5f70\u663e\u4e86\u826f\u597d\u7684\u6291\u5236\u6548\u679c\u3002\u56e0\u6b64\uff0c\u5b83\u4e5f\u66fe\u5148\u540e\u83b7\u5f97\u8fc7\u7f8e\u56fd<\/span> FDA <\/span>\u9881\u53d1\u7684\u7a81\u7834\u6027\u7597\u6cd5\u8ba4\u5b9a\u4e0e\u5b64\u513f\u836f\u8d44\u683c\u3002<\/span><\/span><\/p>\n

 <\/span><\/p>\n

\u836f\u7269\u4fe1\u606f<\/span><\/strong><\/p>\n

\"\u6df1\u5ea6\u9605\u8bfb\uff1a<\/p>\n


<\/p>\n

\u4e34\u5e8a\u7597\u6548<\/span><\/strong><\/p>\n

 <\/span><\/strong><\/p>\n

\u5e03\u5409\u4ed6\u6ee8\u4e00\u79cd\u65b0\u578b\u7684<\/span>ALK\u548c<\/span>EGFR<\/span>\u53cc\u91cd\u6291\u5236\u5242\uff0c\u4e34\u5e8a\u7814\u7a76\u8bc1\u660e\uff0c\u5e03\u5409\u4ed6\u6ee8\u8054\u5408\u6297<\/span>EGFR<\/span>\u6297\u4f53\u4f7f\u7528\u6216\u53ef\u7a81\u7834\u7b2c\u4e09\u4ee3\u9776\u5411\u836f\u5965\u5e0c\u66ff\u5c3c<\/span>(<\/span>\u53c8\u540d\u5361\u5e03\u5b81\u5965\u5e0c\u66ff\u5c3c<\/span>)<\/span>\u8010\u836f\uff0c\u53ef\u5f3a\u6548\u6291\u5236<\/span>ALK<\/span>\u7684<\/span>L1196M<\/span>\u7a81\u53d8\u548c<\/span>EGFR<\/span>\u7684<\/span>T790M<\/span>\u7a81\u53d8\u3002<\/span><\/span><\/p>\n

 <\/span><\/p>\n

\u5173\u4e8e<\/span>EAI-045\u5bf9<\/span>C797S \/ T790M \/ del19<\/span>\u4e09\u91cd\u7a81\u53d8\u7684\u975e\u5c0f\u7ec6\u80de\u80ba\u7ec6\u80de\u662f\u5426\u6709\u6548\u7684\u95ee\u9898\uff0c\u7814\u7a76\u4eba\u5458\u7b5b\u9009\u4e86<\/span>30<\/span>\u79cd\u836f\u7269\u6765\u9274\u5b9a\u4ed6\u4eec\u9488\u5bf9<\/span>C797S \/ T790M \/ del19<\/span>\u4e09\u91cd\u7a81\u53d8<\/span>NSCLC<\/span>\u7ec6\u80de\u7684\u6d3b\u6027\uff0c\u5e76\u53d1\u73b0<\/span>ALK<\/span>\u6291\u5236\u5242\u5e03\u5409\u4ed6\u6ee8\uff08<\/span>brigatinib<\/span>\uff09\u663e\u793a\u51fa\u8fd9\u6837\u7684\u6d3b\u6027\u3002\u5e03\u5409\u4ed6\u6ee8\u4e0d\u4ec5\u5bf9<\/span>T790M<\/span>\u53cc\u7a81\u53d8\u975e\u5c0f\u7ec6\u80de\u80ba\u764c\u5177\u6709\u4e00\u5b9a\u529f\u6548\uff0c\u800c\u4e14\u901a\u8fc7\u5b9e\u9a8c\u53d1\u73b0\u5e03\u5409\u4ed6\u6ee8\u5bf9<\/span>C797S \/ T790M \/ del19<\/span>\u4e09\u91cd\u7a81\u53d8<\/span>NSCLC<\/span>\u7ec6\u80de\u4ee5\u53ca<\/span>T790M \/ del19<\/span>\u53cc\u7a81\u53d8<\/span>NSCLC<\/span>\u7ec6\u80de\u4e5f\u6709\u6d3b\u6027\u3002\u56e0\u6b64\uff0c\u5e03\u5409\u4ed6\u6ee8\u5f88\u53ef\u80fd\u56e0\u4e3a\u514b\u670d<\/span>C797S<\/span>\u7a81\u53d8\u8010\u836f\uff0c\u800c\u6210\u4e3a<\/span>\u201c<\/span>\u7b2c\u56db\u4ee3<\/span>EGFR-TKI<\/span>\u80ba\u764c\u9776\u5411\u836f<\/span>\u201d<\/span>\u3002<\/span><\/span><\/p>\n

 <\/span><\/p>\n

 \u5e03\u5409\u4ed6\u6ee8\u521a\u597d\u514b\u670d\u4e86<\/span>ALK<\/span>\u7a81\u53d8\u4f53\u5bfc\u81f4\u7684\u5bf9\u514b\u5511\u66ff\u5c3c\u7684\u6297\u6027\u3002\u5b83\u662f\u4e00\u79cd\u916a\u6c28\u9178\u9176\u6291\u5236\u5242\uff0c\u5177\u6709\u6297\u591a\u79cd\u6fc0\u9176\uff08\u5305\u62ec<\/span>ALK<\/span>\u3001<\/span>ROS1<\/span>\u3001\u80f0\u5c9b\u7d20\u6837\u751f\u957f\u56e0\u5b50<\/span>-1<\/span>\u53d7\u4f53\u3001<\/span>Flt-3<\/span>\uff09\u4ee5\u53ca\u8868\u9762\u751f\u957f\u56e0\u5b50\u53d7\u4f53\uff08<\/span>EGFR<\/span>\uff09\u7f3a\u5931\u548c\u70b9\u7a81\u53d8\u7684\u6d3b\u6027\u3002\u5728\u4f53\u5916\u5e03\u5409\u4ed6\u6ee8\u5bf9<\/span>ALK<\/span>\u7684\u6291\u5236\u4f5c\u7528\u6bd4\u514b\u5511\u66ff\u5c3c\u9ad8<\/span>12<\/span>\u500d\uff0c\u5bf9<\/span>ALK<\/span>\u7a81\u53d8\u4f53\u6709\u5f88\u9ad8\u7684\u6297\u6027\uff0c\u6545\u800c\u53ef\u4ee5\u7528\u4e8e\u6cbb\u7597\u514b\u5511\u66ff\u5c3c\u6cbb\u7597\u540e\u75c5\u60c5\u8fdb\u5c55\u6216\u4e0d\u8010\u53d7\u7684<\/span>ALK<\/span>\u9633\u6027\u7684\u8f6c\u79fb\u6027\u975e\u5c0f\u7ec6\u80de\u80ba\u764c\u60a3\u8005\u3002<\/span><\/span><\/p>\n

 <\/span><\/p>\n

\u5408\u6210\u8def\u7ebf\uff1a<\/span><\/strong><\/p>\n

 <\/span><\/p>\n

\u4ece\u90bb\u7898\u82ef\u80fa\u51fa\u53d1\uff0c\u5728<\/span>Pd\u50ac\u5316\u4e0b\u4e0e\u4e8c\u7532\u57fa\u6c27\u5316\u81a6\u53cd\u5e94\uff0c\u5f62\u6210<\/span>C-P<\/span>\u952e\u5f97\u5230\u5316\u5408\u7269<\/span>S-3<\/span>\uff0c\u5176\u5728\u78b1\u7684\u53c2\u4e0e\u4e0b\u4e0e\u5316\u5408\u7269<\/span>S-4<\/span>\u7ecf\u8fc7\u4eb2\u6838\u82b3\u9999\u53d6\u4ee3\u53cd\u5e94\u5f97\u5230\u5316\u5408\u7269<\/span>S-5<\/span>\u3002\u5316\u5408\u7269<\/span>S-6<\/span>\u548c<\/span>S-7<\/span>\u7ecf\u8fc7\u4eb2\u6838\u82b3\u9999\u53d6\u4ee3<\/span>\/<\/span>\u6c22\u5316\u8fd8\u539f\u5f97\u5230\u5316\u5408\u7269<\/span>S-9<\/span>\u3002\u968f\u540e<\/span>S-9<\/span>\u4e0e<\/span>S-5<\/span>\u7ecf\u8fc7\u4eb2\u6838\u82b3\u9999\u53d6\u4ee3\u53cd\u5e94\u5f97\u5230<\/span>brigatinib(Alunbrig,<\/span><\/span> <\/span>\u5e03\u5409\u4ed6\u6ee8<\/span>)\u3002<\/span><\/span><\/p>\n


<\/p>\n

\"\u6df1\u5ea6\u9605\u8bfb\uff1a<\/p>\n

\u53c2\u8003\uff1a<\/span>WO2016065028A1<\/span><\/p>\n


<\/p>\n


<\/p>\n

\n
\u5728\u7814 ALK\u6291\u5236\u5242<\/span><\/section>\n
<\/section>\n
<\/section>\n<\/section>\n


<\/p>\n


<\/p>\n

1. <\/span>\u7b2c\u4e09\u4ee3<\/span>ALK\u6291\u5236\u5242<\/span>—<\/span><\/span><\/strong>\u52b3\u62c9\u66ff\u5c3c\uff08<\/span><\/strong>Lorlatinib<\/span><\/strong>\uff09<\/span><\/strong><\/p>\n


<\/p>\n

\"\u6df1\u5ea6\u9605\u8bfb\uff1a<\/p>\n


<\/p>\n


<\/p>\n

\u7b2c\u4e09\u4ee3<\/span>ALK\u6291\u5236\u5242<\/span>Lorlatinib\uff08\u52b3\u62c9\u66ff\u5c3c\uff09\uff0c\u5b83\u662f\u8f89\u745e\u516c\u53f8\u5f00\u53d1\u7684\u4e00\u79cd\u65b0\u578b\u3001\u53ef\u9006\u3001\u5f3a\u6548\u5c0f\u5206\u5b50<\/span>ALK<\/span>\u548c<\/span>ROS1<\/span>\u6291\u5236\u5242\uff0c\u5176\u5bf9<\/span>ALK<\/span>\u5df2\u77e5\u7684\u8010\u836f\u7a81\u53d8\u5747\u5177\u6709\u5f88\u5f3a\u7684\u6291\u5236\u4f5c\u7528\uff0c\u53ef\u6291\u5236\u514b\u5511\u66ff\u5c3c\u8010\u836f\u7684<\/span>9\u79cd\u7a81\u53d8\uff0c\u5177\u6709\u8f83\u5f3a\u7684\u8840\u8111\u5c4f\u969c\u900f\u8fc7\u80fd\u529b\uff0c\u5165\u8111\u6548\u679c\u8f83\u5f3a\uff0c\u7279\u522b\u9002\u5408\u5bf9\u5176\u4ed6<\/span>ALK<\/span>\u8010\u836f\u7684\u665a\u671f<\/span>NSCLC<\/span>\u60a3\u8005\u3002<\/span><\/span><\/p>\n

 <\/span><\/p>\n

2016\u5e74<\/span>6<\/span>\u6708<\/span>5<\/span>\u65e5\uff0c\u8f89\u745e\u5728<\/span>ASCO<\/span>\u4f1a\u8bae\u4e0a\u516c\u5e03\u4e86\u8be5\u836f\u7684<\/span>I\/II<\/span>\u671f\u4e34\u5e8a\u7814\u7a76\u6570\u636e\uff0c\u5165\u7ec4\u7684<\/span>54<\/span>\u4f8b\u60a3\u8005\u6709<\/span>41<\/span>\u4f8b\u4e3a<\/span>ALK<\/span>\u9633\u6027\uff0c<\/span>12<\/span>\u4f8b\u4e3a<\/span>ROS<\/span>\u9633\u6027\uff0c\u5176\u4e2d<\/span>39<\/span>\u4f8b\u6709\u8111\u8f6c\u79fb\u3002\u8be5\u4e34\u5e8a\u8bd5\u9a8c\u6700\u7ec8\u786e\u5b9a\u7684\u7ed9\u836f\u65b9\u6848\u4e3a\u6bcf\u65e5<\/span>1<\/span>\u6b21<\/span>100mg<\/span>\uff0c\u60a3\u8005\u7684\u603b\u5e94\u7b54\u7387\u4e3a<\/span>46%<\/span>\uff0c<\/span>3<\/span>\u4f8b\u5b9e\u73b0\u5b8c\u5168\u5e94\u7b54\uff0c<\/span>16<\/span>\u4f8b\u5b9e\u73b0\u90e8\u5206\u5e94\u7b54\uff0c\u4e2d\u4f4d<\/span>PFS<\/span>\u4e3a<\/span>11.4<\/span>\u4e2a\u6708\uff0c\u53e6\u5916\u8fd8\u663e\u793a\u51fa\u7f29\u5c0f\u8f6c\u79fb\u6027\u7684\u8111\u90e8\u80bf\u7624\u4f53\u79ef\u7684\u6548\u679c\u3002<\/span><\/span><\/p>\n

 <\/span><\/p>\n

2017\u5e74<\/span>4<\/span>\u6708<\/span>27<\/span>\u65e5\uff0c\u8f89\u745e\u516c\u53f8\u5ba3\u5e03\u5176\u65b0\u4e00\u4ee3<\/span>ALK\/ROS1<\/span>\u6291\u5236\u5242<\/span>Lorlatinib<\/span>\u88ab<\/span>FDA<\/span>\u6388\u4e88\u7a81\u7834\u6027\u836f\u7269\u8d44\u683c\uff0c\u7528\u4e8e\u65e2\u5f80\u63a5\u53d7\u8fc7\u4e00\u79cd\u6216\u591a\u79cd<\/span>ALK<\/span>\u6291\u5236\u5242\u6cbb\u7597\uff0c\u6cbb\u7597\u540e\u75be\u75c5\u8fdb\u5c55\u7684\u3001<\/span>ALK<\/span>\u9633\u6027\u3001\u8f6c\u79fb\u6027<\/span>NSCLC<\/span>\u3002\u8fd9\u4e00\u8d44\u683c\u7684\u6388\u4e88\u662f\u57fa\u4e8e\u4e00\u9879\u6b63\u5728\u8fdb\u884c\u7684<\/span>1\/2<\/span>\u671f\u4e34\u5e8a\u7814\u7a76\u7684\u7597\u6548\u548c\u5b89\u5168\u6027\u6570\u636e\u3002\u7528\u4e8e\u4e8c\u7ebf\u6cbb\u7597<\/span>ALK<\/span>\uff08\u95f4\u53d8\u6027\u6dcb\u5df4\u7624\u6fc0\u9176\uff09\u9633\u6027\u7684\u8f6c\u79fb\u6027\u975e\u5c0f\u7ec6\u80de\u80ba\u764c\uff08<\/span>NSCLC<\/span>\uff09<\/span><\/span><\/p>\n

 <\/span><\/p>\n

2018\u5e74<\/span>2<\/span>\u6708<\/span>12<\/span>\u65e5\uff0c\u8f89\u745e\u5ba3\u5e03<\/span>FDA<\/span>\u53d7\u7406\u4e86<\/span>lorlatinib<\/span>\u7528\u4e8e\u6cbb\u7597\u65e2\u5f80\u63a5\u53d7\u8fc7\u81f3\u5c11\u4e00\u79cd<\/span>ALK<\/span>\u6291\u5236\u5242\u7684\u8f6c\u79fb\u6027<\/span>ALK<\/span>\u9633\u6027\u975e\u5c0f\u7ec6\u80de\u80ba\u764c\u60a3\u8005\u7684\u4e0a\u5e02\u7533\u8bf7\uff0c\u5e76\u6388\u4e88\u4e86\u4f18\u5148\u5ba1\u8bc4\u8d44\u683c\u3002<\/span>lorlatinib<\/span>\u9884\u8ba1\u5728\u4eca\u5e74<\/span>8<\/span>\u6708\u53ef\u83b7\u6279\u4e0a\u5e02\u3002<\/span><\/span><\/p>\n

 <\/span><\/strong><\/p>\n

\u836f\u7269\u4fe1\u606f<\/span><\/strong><\/p>\n

\"\u6df1\u5ea6\u9605\u8bfb\uff1a<\/p>\n

 <\/span><\/strong>
<\/p>\n

\u4e34\u5e8a\u7597\u6548<\/span><\/strong><\/p>\n

 <\/span><\/strong><\/p>\n

\u7b2c\u4e09\u4ee3<\/span>ALK\u6291\u5236\u5242<\/span>–Lorlatinib<\/span>\u3002\u4f5c\u4e3a\u65b0\u4e00\u4ee3<\/span>ALK\/ROS1<\/span>\u916a\u6c28\u9178\u6fc0\u9176\u6291\u5236\u5242\uff0c<\/span>lorlatinib<\/span>\u4e13\u95e8\u7528\u4e8e\u6291\u5236\u53ef\u4ee5\u9a71\u4f7f\u80bf\u7624\u5bf9\u5176\u5b83<\/span>ALK<\/span>\u6291\u5236\u5242\u8010\u836f\u5e76\u7a7f\u900f\u8840\u8111\u5c4f\u969c\u7684\u57fa\u56e0\u7a81\u53d8\uff0c\u5728<\/span>2<\/span>\u671f\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\u663e\u793a\u51fa\u5bf9\u80ba\u80bf\u7624\u548c\u8111\u8f6c\u79fb\u7684\u6301\u4e45\u7597\u6548\u3002<\/span><\/span><\/p>\n

 <\/span><\/p>\n

\u8be5\u8bd5\u9a8c\u5305\u542b\u4e86<\/span>275\u540d<\/span>NSCLC<\/span>\u60a3\u8005\uff0c\u6839\u636e\u751f\u7269\u6807\u5fd7\u7269\uff08<\/span>ALK<\/span>\u9633\u6027\u6216<\/span>ROS1<\/span>\u9633\u6027\uff09\u548c\u4e4b\u524d\u7684\u6cbb\u7597\u88ab\u5f52\u4e3a<\/span>6<\/span>\u4e2a\u961f\u5217\u3002\u8bd5\u9a8c\u6570\u636e\u8868\u660e\uff1a<\/span>Lorlatinib<\/span>\u5728\u672a\u7ecf\u6cbb\u7597\u7684<\/span>ALK<\/span>\u9633\u6027\u60a3\u8005\u4e2d\u7684\u603b\u7f13\u89e3\u7387\uff08<\/span>ORR<\/span>\uff09\u4e3a<\/span>90%<\/span>\uff0c\u540c\u65f6\u5176\u9885\u5185\u603b\u7f13\u89e3\u7387\uff08<\/span>IC-ORR<\/span>\uff09\u4e3a<\/span>75%<\/span>\uff1b<\/span><\/span><\/p>\n

\u5bf9\u4e8e\u65e2\u5f80\u4ee5\u514b\u5511\u66ff\u5c3c\u6cbb\u7597\u8fc7\u7684<\/span>ALK\u9633\u6027\u60a3\u8005\uff0c\u4e0d\u7ba1\u662f\u5426\u6709\u8fc7\u5316\u7597\uff0c<\/span>Lorlatinib<\/span>\u6cbb\u7597\u7684\u603b\u7f13\u89e3\u7387\u4e3a<\/span>69%<\/span>\uff0c\u9885\u5185\u603b\u7f13\u89e3\u7387\u4e3a<\/span>68%<\/span>\uff1b\u5728\u65e2\u5f80\u4ee5\u975e\u514b\u5511\u66ff\u5c3c<\/span>ALK<\/span>\u6291\u5236\u5242\u6cbb\u7597\u8fc7\u7684<\/span>ALK<\/span>\u9633\u6027\u60a3\u8005\u4e2d\uff0c\u4e0d\u7ba1\u662f\u5426\u6709\u8fc7\u5316\u7597\uff0c\u5176\u603b\u7f13\u89e3\u7387\u4e3a<\/span>33%<\/span>\uff1b\u800c\u5bf9\u4e8e<\/span>ROS1<\/span>\u9633\u6027\u60a3\u8005\u3002\u4e0d\u7ba1\u4ee5\u524d\u662f\u5426\u63a5\u53d7\u8fc7\u6cbb\u7597\uff0c\u5176\u603b\u7f13\u89e3\u7387\u4e3a<\/span>36%<\/span>\u3002<\/span><\/span><\/p>\n

 <\/span><\/p>\n

2. <\/span>Entrectinib\uff08<\/span>RXDX-101<\/span>\uff09<\/span><\/span><\/strong><\/p>\n


<\/p>\n

\"\u6df1\u5ea6\u9605\u8bfb\uff1a<\/p>\n


<\/p>\n

Entrectinib \u662f<\/span>\u4e00\u6b3e\u5728\u7814\u7684<\/span>\u65b0\u578b\u3001\u53e3\u670d\u6709\u6548\u7684\u3001\u5177\u6709\u4e2d\u67a2\u795e\u7ecf\u7cfb\u7edf<\/span>(CNS)\u6d3b\u6027\u7684\u916a\u6c28\u9178\u6fc0\u9176\u6291\u5236\u5242<\/span>(TKI)<\/span>\uff0c\u9776\u5411\u6cbb\u7597\u643a\u5e26 <\/span>NTRK1\/2\/3(<\/span>\u7f16\u7801 <\/span>TRKA\/TRKB\/TRKC)<\/span>\u3001<\/span>ROS1 <\/span>\u548c <\/span>ALK <\/span>\u878d\u5408\u57fa\u56e0\u7a81\u53d8\u7684\u5b9e\u4f53\u7624\u60a3\u8005\u3002\u503c\u5f97\u4e00\u63d0\u7684\u662f\uff0c<\/span>entrectinib <\/span>\u53ef\u4ee5\u901a\u8fc7\u8840\u8111\u5c4f\u969c\uff0c\u8be5\u836f\u662f\u4e34\u5e8a\u4e0a\u552f\u4e00\u4e00\u79cd\u88ab\u8bc1\u660e\u9488\u5bf9\u539f\u53d1\u6027\u548c\u8f6c\u79fb\u6027\u4e2d\u67a2\u795e\u7ecf\u7cfb\u7edf<\/span>(CNS)<\/span>\u75be\u75c5\u5177\u6709\u7597\u6548\u7684 <\/span>TRK <\/span>\u6291\u5236\u5242\uff0c\u5e76\u4e14\u6ca1\u6709\u4e0d\u826f\u7684\u8131\u9776\u6d3b\u6027<\/span>(off-target activity)<\/span>\u3002<\/span><\/span><\/p>\n

 <\/span><\/p>\n

\u76ee\u524d\uff0c<\/span>entrectinib \u6b63\u5904\u4e8e <\/span>II <\/span>\u671f\u4e34\u5e8a\u7814\u7a76 <\/span>STARTRK-2<\/span>\uff0c\u8be5\u7814\u7a76\u662f\u4e00\u9879\u5168\u7403\u6027\u3001\u591a\u4e2d\u5fc3\u3001\u5f00\u653e\u6807\u7b7e\u7814\u7a76\uff0c\u91c7\u7528\u4e00\u7ec4\u8bbe\u8ba1\u6765\u5bf9\u60a3\u8005\u80bf\u7624\u6837\u672c\u4e2d\u7684\u76f8\u5173\u9776\u6807\u8fdb\u884c\u7b5b\u67e5\u3002\u8fd9\u79cd\u7b5b\u67e5\u6a21\u5f0f\uff0c\u65e8\u5728\u5145\u5206\u5229\u7528 <\/span>entrectinib <\/span>\u5728\u6a2a\u8de8\u4e00\u7cfb\u5217\u4e0d\u540c\u7c7b\u578b\u80bf\u7624\u548c\u5206\u5b50\u9776\u6807\u4e2d\u5df2\u88ab\u8bc1\u660e\u7684\u521d\u6b65\u7597\u6548\u3002\u6839\u636e\u6b64\u524d\u516c\u5e03\u7684 <\/span>I <\/span>\u671f\u4e34\u5e8a\u7814\u7a76\u6570\u636e\uff0c<\/span>entrectinib <\/span>\u5728\u643a\u5e26 <\/span>NTRK<\/span>\u3001<\/span>ROS1<\/span>\u3001<\/span>ALK <\/span>\u878d\u5408\u57fa\u56e0\u7a81\u53d8\u9633\u6027\u7684\u9885\u5916\u75be\u75c5\u60a3\u8005<\/span>(n=24)<\/span>\u4e2d\u5b9e\u73b0\u4e86\u9ad8\u8fbe <\/span>79% <\/span>\u7684\u5ba2\u89c2\u7f13\u89e3\u7387<\/span>(ORR)<\/span>\uff0c\u5e76\u4e14\u5728\u4e2d\u67a2\u795e\u7ecf\u7cfb\u7edf<\/span>(CNS)<\/span>\u75be\u75c5\u7684\u60a3\u8005\u4e2d\u4e5f\u5b9e\u73b0\u4e86\u5b8c\u5168\u7684\u3001\u53ef\u6301\u7eed\u7684\u7f13\u89e3\u3002<\/span><\/span><\/p>\n

 <\/span><\/p>\n

3. <\/span>Ensartinib\uff08<\/span>X-396<\/span>\uff09<\/span><\/span><\/strong><\/p>\n


<\/p>\n

\"\u6df1\u5ea6\u9605\u8bfb\uff1a<\/p>\n


<\/p>\n

Ensartinib<\/span>\u4ee3\u53f7\u4e3a<\/span>X-396<\/span>\uff0c\u6027\u72b6\u4e3a\u80f6\u56ca\uff0c\u7531\u8d1d\u8fbe\u836f\u4e1a\u63a7\u80a1\u5b50\u516c\u53f8\u7f8e\u56fd<\/span>Xcovery Holding Company LLC<\/span>\u5f00\u53d1\u3002<\/span>Ensartinib<\/span>\u662f\u9488\u5bf9\u80ba\u764c\u6cbb\u7597\u7684\u65b0\u4e00\u4ee3<\/span>ALK<\/span>\u6291\u5236\u5242\uff0c\u5177\u6709\u6297<\/span>ALK<\/span>\u7684\u6d3b\u6027\uff0c\u7528\u4e8e\u6cbb\u7597\u6709<\/span>ALK<\/span>\u7a81\u53d8\u7684\u80ba\u764c\u60a3\u8005\uff0c\u6b64\u5916\u4e5f\u53ef\u9776\u5411<\/span>MET<\/span>\u3001<\/span>ABL<\/span>\u3001<\/span>Axl<\/span>\u3001<\/span>EPHA2<\/span>\u3001<\/span>LTK<\/span>\u3001<\/span>ROS1<\/span>\u548c<\/span>SLK<\/span>\u3002<\/span>
<\/p>\n

\u4e0e\u4e4b\u524d<\/span>ALK\u7684\u9776\u5411\u836f\u7269\u76f8\u6bd4\u8f83\uff0c<\/span>Ensartinib\u7684\u4e0d\u826f\u53cd\u5e94\u5c0f\u4e8e\u514b\u5511\u66ff\u5c3c\uff0c<\/span>ALK<\/span>\u6d3b\u6027\u8fdc\u6bd4\u514b\u5511\u66ff\u5c3c\u5f3a\uff0c\u5bf9\u8111\u8f6c\u79fb\u60a3\u8005\u7684\u7597\u6548\u5f3a\u4e8e\u514b\u5511\u66ff\u5c3c\uff0c\u4f46\u6570\u636e\u4ecd\u4e0d\u5145\u5206\uff0c\u76ee\u524d\u65e0\u6cd5\u4e0e\u5176\u5b83\u4e8c\u4ee3<\/span>ALK-TKI<\/span>\u7684\u5165\u8111\u80fd\u529b\u6bd4\u8f83\uff0c\u5bf9\u8111\u819c\u8f6c\u79fb\u60a3\u8005\u7684\u7597\u6548\u5e94\u8be5\u6b20\u4f73\u3002<\/span>Ensartinib<\/span>\u53ef\u4ee5\u5bf9\u4ed8\u8272\u745e\u66ff\u5c3c\u7684\u8010\u836f\u7a81\u53d8<\/span>F1174<\/span>\u3001<\/span>L1152<\/span>\u3001<\/span>1151Tins<\/span>\u548c<\/span>T1151M<\/span>\uff0c\u5bf9<\/span>G1202R<\/span>\u7a81\u53d8\u4e5f\u6709\u4e2d\u7b49\u6d3b\u6027\u3002\u5c31\u76ee\u524d\u7684\u6570\u636e\u63a8\u6d4b\uff0c<\/span>Ensartinib<\/span>\u53ef\u5e94\u7528\u4e8e\u514b\u5511\u66ff\u5c3c\u6216\u8272\u745e\u66ff\u5c3c\u8010\u836f\u4e14\u975e\u8111\u819c\u8f6c\u60a3\u8005\u3002<\/span><\/span><\/p>\n

2018\u5e74<\/span>3\u6708\uff0c\u7f8e\u56fd\u764c\u75c7\u7814\u7a76\u534f\u4f1a\u53d1\u5e03\u4e86\u5c0f\u7ec6\u80de\u80ba\u764c\u65b0\u836f<\/span>Ensartinib<\/span>\u7684\u4e34\u5e8a<\/span>II<\/span>\u671f\u5b9e\u9a8c\u62a5\u544a\uff0c\u7ed3\u679c\u663e\u793a\uff1a\u4ee5<\/span>Ensartinib<\/span>\u4e0e\u514b\u5511\u66ff\u5c3c\u4f5c\u5bf9\u6bd4\uff0c\u670d\u7528\u514b\u5511\u66ff\u5c3c\u6cbb\u7597\u7684\u60a3\u8005\u6709\u6548\u7387\u662f<\/span>69%<\/span>\uff0c\u800c<\/span>Ensartinib<\/span>\u5bf9<\/span>ALK\u9633\u6027\u60a3\u8005\u7684\u75be\u75c5\u63a7\u5236\u7387\u8fbe\u5230\u4e86<\/span>81.7%<\/span>\uff0c<\/span>80%<\/span>\u7684\u60a3\u8005\u80bf\u7624\u6d88\u9000<\/span><\/strong>\u3002<\/span><\/span><\/p>\n

 <\/span><\/p>\n

4. <\/span>\u7b2c\u56db\u4ee3<\/span>ALK\u6291\u5236\u5242<\/span>\u2014\u2014<\/span>\u6d1b\u666e\u66ff\u5c3c<\/span>(TPX-0005<\/span>\u3001<\/span>Ropotrectinib)<\/span><\/strong><\/span><\/p>\n


<\/p>\n

\n


<\/p>\n

TPX-0005(\u6d1b\u666e\u66ff\u5c3c<\/span>)<\/span>\u662f\u7531<\/span>TP Therapeutics<\/span>\u516c\u53f8\u7814\u53d1\u7684\u7b2c\u56db\u4ee3<\/span>ALK<\/span>\u6291\u5236\u5242\uff0c\u636e<\/span>TP Therapeutics<\/span>\u516c\u53f8\u5728<\/span>2016<\/span>\u5e74<\/span>AACR<\/span>\u5e74\u4f1a\u62a5\u544a\u79f0\uff0c<\/span>TPX-0005<\/span>\u4e0d\u4ec5\u662f\u4e00\u79cd\u5e7f\u8c31\u7684<\/span>ALK<\/span>\u7a81\u53d8\u6291\u5236\u5242\uff0c\u8fd8\u53ef\u901a\u8fc7\u6291\u5236<\/span>SRC<\/span>\u514b\u670d\u539f\u53d1\u8010\u836f\u53ca\u8f6c\u79fb\u6027\u7279\u5f81\uff0c\u5e76\u4e14\u7279\u522b\u5177\u6709\u89e3\u51b3\u4e34\u5e8a\u4e0a<\/span>ALK<\/span>\u8010\u836f\u673a\u5236\u7684\u6f5c\u529b\uff0c\u5305\u62ec\u7ee7\u53d1\u6027\u8010\u836f\u7a81\u53d8\u3001\u65c1\u8def\u548c\u4e0b\u6e38\u901a\u8def\u7684\u6fc0\u6d3b\u3001\u4e0a\u76ae\u95f4\u5145\u8d28\u8f6c\u5316\u7b49\u3002\u8be5\u836f\u5c06\u4e3a\u4e34\u5e8a\u6cbb\u7597\u63d0\u4f9b\u65b0\u7684\u673a\u4f1a\uff0c\u6291\u5236<\/span>ALK<\/span>\u3001<\/span>ROS1<\/span>\u6216<\/span>TRK<\/span>\u5bb6\u65cf\u5728\u5b9e\u4f53\u6076\u6027\u80bf\u7624\u4e2d\u7684\u5f02\u5e38\u4fe1\u53f7\u4f20\u5bfc\uff0c\u514b\u670d\u96be\u6cbb\u6027\u60a3\u8005\u7684\u591a\u91cd\u8010\u836f\u6027\u673a\u5236\u3002<\/span><\/span><\/p>\n

 <\/span><\/p>\n

2017\u5e74<\/span>6<\/span>\u6708<\/span>28<\/span>\u65e5\uff0c<\/span>TP Therapeutics<\/span>\u516c\u53f8\u5ba3\u5e03<\/span>FDA<\/span>\u5df2\u7ecf\u5411\u5176\u5728\u7814\u4e34\u5e8a\u65b0\u836f\u5316\u5408\u7269<\/span>TPX-0005<\/span>\u9881\u53d1\u4e86\u5b64\u513f\u836f\u8d44\u683c\uff0c\u7528\u4e8e\u6cbb\u7597\u643a\u5e26<\/span>ALK<\/span>\u3001<\/span>ROS1<\/span>\u6216<\/span>NTRK<\/span>\u81f4\u764c\u57fa\u56e0\u91cd\u6392\u7684<\/span>NSCLC<\/span>\u60a3\u8005\u3002<\/span>TPX-0005<\/span>\u76ee\u524d\u6b63\u5904\u4e8e<\/span>1\/2<\/span>\u671f\u3001\u5f00\u653e\u6807\u7b7e\u3001\u591a\u4e2d\u5fc3\u4e34\u5e8a\u7814\u7a76\u8bd5\u9a8c\u9636\u6bb5\uff0c\u5728<\/span>ALK<\/span>\u3001<\/span>ROS1<\/span>\u6216<\/span>NTRK1-3<\/span>\u91cd\u6392\u7a81\u53d8\u665a\u671f\u5b9e\u4f53\u7624\u60a3\u8005\u7fa4\u4f53\u4e2d\u8bc4\u4f30\u5b89\u5168\u6027\u3001\u8010\u53d7\u6027\u3001\u836f\u4ee3\u52a8\u529b\u5b66\u548c\u6297\u80bf\u7624\u6d3b\u6027\u3002<\/span><\/span><\/p>\n

 <\/span><\/p>\n

\u4e34\u5e8a\u7597\u6548\uff1a<\/span><\/strong><\/p>\n

 <\/span><\/strong><\/p>\n

\u6d1b\u666e\u66ff\u5c3c<\/span>(Ropotrectinib\uff0c<\/span>TPX-0005)<\/span>\u4f5c\u4e3a\u65b0\u4e00\u4ee3\u7684<\/span>ROS1\/TRKA-C\/ALK<\/span>\u6291\u5236\u5242\u83b7\u5f97\u521d\u6b65\u4e34\u5e8a\u6548\u679c\uff1a<\/span>14<\/span>\u540d<\/span>ALK NSCLC<\/span>\uff0c<\/span>4<\/span>\u540d\u60a3\u8005\u7a33\u5b9a\u3002\u5bf9\u672a\u7ecf<\/span>ROS1-TKI<\/span>\u6cbb\u7597\u7684\u603b\u6709\u6548\u7387\u4e3a<\/span>70%;<\/span>\u5bf9<\/span>ROS1-TKI<\/span>\u8010\u836f\u7684\u603b\u6709\u6548\u7387\u4e3a<\/span>11%<\/span>\u3002\u5bf9\u4e8e<\/span>NTRK<\/span>\u878d\u5408\u9633\u6027\u5b9e\u4f53\u7624\uff0c\u5305\u62ec<\/span>1<\/span>\u4f8b<\/span>NTRK<\/span>\u878d\u5408\u9633\u6027\u7c7b\u4f3c\u53d1\u751f\u4e8e\u4e73\u817a\u7684\u5206\u6ccc\u6027\u80bf\u7624\uff0c\u6d1b\u666e\u66ff\u5c3c\u5747\u521d\u6b65\u8868\u73b0\u51fa\u4e86\u80bf\u7624\u6291\u5236\u529b<\/span>;<\/span>\u6d1b\u666e\u66ff\u5c3c\u8010\u53d7\u6027\u826f\u597d\uff0c\u63a5\u53d7\u6cbb\u7597\u7684\u60a3\u8005\u51fa\u73b0\u7684\u4e0d\u826f\u4e8b\u4ef6\u5927\u591a\u4e3a<\/span>1-2<\/span>\u7ea7\uff0c\u5728\u53ef\u63a5\u53d7\u8303\u56f4\u5185\u3002<\/span><\/span><\/p>\n


<\/span><\/span><\/p>\n

TPX-0005\u62e5\u6709\u4e00\u79cd\u7d27\u51d1\u7684\u4e09\u7ef4\u5927\u73af\u5206\u5b50\u7ed3\u6784\uff0c\u5206\u5b50\u91cf\u4e3a<\/span>355.37<\/span>\uff0c\u6bd4\u73b0\u6709\u7684\u6240\u6709<\/span>ALK<\/span>\u548c<\/span>ROS1<\/span>\u6291\u5236\u5242\u5206\u5b50\u91cf\u66f4\u5c0f\u3002<\/span>TPX-0005<\/span>\u7684\u7d27\u51d1\u7684\u5c0f\u5206\u5b50\u7ed3\u6784\u4f7f\u5b83\u5728<\/span>ATP<\/span>\u5185\u90e8\u4e0e\u4e2d\u5fc3\u7ed3\u5408\u4f4d\u70b9\u6709\u6548\u7ed3\u5408\uff0c\u5e76\u4e14\u907f\u514d<\/span>ATP<\/span>\u7ed3\u5408\u4f4d\u70b9\u4e4b\u5916\u7684\u7a81\u53d8\u9020\u6210\u7684\u7a7a\u95f4\u4f4d\u963b\uff0c\u5373\u907f\u514d\u4e34\u5e8a\u8010\u836f\u7a81\u53d8\u7684\u5e72\u6270\u3002\u53e6\u5916\uff0c<\/span>TPX-0005<\/span>\u7684\u5206\u5b50\u6bd4\u73b0\u6709\u7684\u6240\u6709<\/span>ALK<\/span>\u548c<\/span>ROS1<\/span>\u6291\u5236<\/span><\/span>\u5242\u5206\u5b50\u91cf\u66f4\u5c0f\uff0c\u5f88\u53ef\u80fd\u5177\u5907\u4e0d\u5f31\u4e8e<\/span>Lorlatinib<\/span>\u7684\u5f3a\u5927\u7a7f\u900f\u8840\u8111\u5c4f\u969c\u80fd\u529b\u3002<\/span><\/span><\/p>\n

 <\/span><\/p>\n

\u7ed3\u8bed<\/span><\/strong><\/span><\/p>\n

 <\/strong><\/span><\/p>\n

ALK\u9633\u6027<\/span>NSCLC<\/span>\u60a3\u8005\u867d\u7136\u5728\u4f7f\u7528<\/span><\/span>\u7b2c\u4e00\u4ee3<\/span>\u514b\u5511\u66ff\u5c3c\u6cbb\u7597\u521d\u671f\u663e\u793a\u51fa\u5f88\u597d\u7684\u7597\u6548\uff0c<\/span>\u4f46\u4e0d\u53ef\u907f\u514d\u7684\u8010\u836f\u95ee\u9898\u6781\u5927\u5730\u9650\u5236\u4e86\u5176\u4e34\u5e8a\u5e94\u7528\u3002\u65b0\u578b<\/span> ALK \u6291\u5236\u5242\u4e0d\u4ec5\u53ef\u4ee5\u514b\u670d\u514b\u5511\u66ff\u5c3c\u7684\u8010\u836f\u7a81\u53d8\uff0c\u5e76\u5728\u5404\u671f\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\u663e\u793a\u51fa\u5bf9\u4e2d\u67a2\u7cfb\u7edf\u75be\u75c5\u8f6c\u79fb\u7684\u60a3\u8005\u6709\u8f83\u597d\u7684\u7597\u6548\u3002\u65b0\u4e00\u4ee3<\/span>ALK <\/span>\u6291\u5236\u5242\u5c42\u51fa\u4e0d\u7a77\uff0c\u4e3a <\/span>ALK <\/span>\u9633\u6027\u7684\u60a3\u8005\u63d0\u4f9b\u4e86\u66f4\u591a\u7684\u6cbb\u7597\u9009\u62e9\u3002\u4f46\u5982\u4f55\u6839\u636e\u8010\u836f\u7a81\u53d8\u9009\u62e9\u5408\u9002\u7684\u65b0\u578b <\/span>ALK <\/span>\u6291\u5236\u5242\u3001\u662f\u5426\u53ef\u53d6\u4ee3\u514b\u5511\u66ff\u5c3c\u4f5c\u4e3a\u4e00\u7ebf\u6cbb\u7597\u3001<\/span>ALK <\/span>\u6291\u5236\u5242\u4e0e\u5316\u7597\u6216\u514d\u75ab\u6cbb\u7597\u7684\u8054\u5408\u65b9\u5f0f\u4ee5\u53ca\u65b0\u578b <\/span>ALK <\/span>\u6291\u5236\u5242\u8010\u836f\u7b49\u4e00\u7cfb\u5217\u95ee\u9898\uff0c\u4ecd\u6709\u5f85\u4e34\u5e8a\u8fdb\u4e00\u6b65\u6df1\u5165\u7814\u7a76\u3002\u6211\u4eec\u671f\u671b\u5728\u7cbe\u51c6\u9776\u5411\u6cbb\u7597\u7684\u6307\u5bfc\u4e0b\uff0c<\/span>ALK <\/span>\u9633\u6027 <\/span>NSCLC <\/span>\u60a3\u8005\u80fd\u591f\u5f97\u5230\u66f4\u9ad8\u6548\u3001\u66f4\u5b89\u5168\u7684 <\/span>ALK <\/span>\u6291\u5236\u5242\u7684\u6cbb\u7597\uff0c\u8fdb\u800c\u66f4\u597d\u5730\u5ef6\u957f\u751f\u5b58\u65f6\u95f4\uff0c\u6539\u5584\u751f\u6d3b\u8d28\u91cf\u3002<\/span><\/span><\/p>\n

 <\/strong><\/p>\n

\u6392\u7248\uff1aHerman<\/span><\/p>\n

\n
\n
\u5e7f\u800c\u544a\u4e4b<\/section>\n<\/section>\n<\/section>\n
\n
\n

\u2299 \u540c\u5199\u610f\u57f9\u8bad<\/span><\/p>\n

\u5199\u610f\u8bba\u575b\u4e28\u65b0\u836f\u4e2d\u7f8e\u53cc\u62a5\u4e4b\u5236\u5242\u6eb6\u51fa\u6280\u672f\u5f00\u53d1<\/a><\/span><\/p>\n

\u5199\u610f\u8bba\u575b\u4e28\u56fd\u9645\u89c4\u8303\u4e0b\u751f\u7269\u836f\u5168\u751f\u547d\u5468\u671f\u8d28\u91cf\u7ba1\u7406<\/a><\/span><\/p>\n

\u5199\u610f\u516c\u76ca\u4e28\u4eff\u5236\u836f\u4e00\u81f4\u6027\u8bc4\u4ef7\u5927\u76d8\u70b9\u4e0e\u603b\u51b3\u6218<\/a><\/p>\n

\u6ee1\u8db3IND\/NDA\u4e2d\u7f8e\u53cc\u62a5\u7684\u53e3\u670d\u65b0\u836f\u5236\u5242\u7814\u53d1<\/a><\/span><\/p>\n<\/section>\n<\/section>\n

\n

\"\u6df1\u5ea6\u9605\u8bfb\uff1a<\/p>\n

\u836f\u4e8b\u7eb5\u6a2a\u662f\u4e00\u4e2a\u5f00\u653e\uff0c\u7531\u81ea\u613f\u8005\u7ec4\u6210\u7684\u56e2\u4f53\uff0c\u73b0\u6709\u6210\u545831\u540d\uff0c\u5206\u522b\u4e3aVoyager88\uff08\u9b4f\u5229\u519b\uff09\uff0c\u96f7\u8bfa\u5c9b\uff0cHerman\uff0c\u6885\u5e0c\uff0c\u6587\u7af9\uff0cduke\uff0cyhqqqqq\uff0c\u5360\u5c0f\u5175\uff0c\u9526\u5fc3\u7ee3\u53e3\uff0cflydp511\uff0c\u5de7\u5de7\uff0c\u9621\u4e0a\u964c\u964c\uff0c\u591a\u5df4\u80fa\uff0c\u745c\u513f\uff0cKailyn\uff0cSeven\uff0c\u5b50\u708e\uff0c\u514b\u683c\u83ab\uff0cVicky\uff0cSophia \uff0c\u4f9d\u7136\u7279\u96f7\u897f\uff0c\u5076\u9635\u96e8\uff0cAimee\uff0c\u4ed6\u5c71\u4e4b\u77f3\uff0c\u96f6\u4e0b274\u2103\uff0cBreathless\uff0cLuffy\uff0c\u80e1\u4e0d\u559c\uff0c Helen\uff0c\u843d\u843d\uff0cSUNRISE\u3002\u6b22\u8fce\u6709\u5fd7\u4e4b\u58eb\u52a0\u5165\u6211\u4eec\u56e2\u961f\u3002\u6295\u7a3f\u3001\u5408\u4f5c\u3001\u52a0\u4e13\u4e1a\u7fa4\u8bf7\u52a0\u5fae\u4fe1442015666\uff0c\u836f\u4e8b\u7eb5\u6a2a\u4e8c\u5343\u4ebaQQ\u7fa422711855\u3002<\/span><\/p>\n

\n

\u59cb\u53d1\u4e8e\u5fae\u4fe1\u516c\u4f17\u53f7\uff1a \u836f\u4e8b\u7eb5\u6a2a <\/p>\n<\/blockquote>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

\u80ba\u764c\u662f\u5168\u7403\u764c\u75c7\u6b7b\u4ea1\u7684\u4e3b\u8981\u539f\u56e0\uff0c\u4e5f\u662f\u4e2d\u56fd\u764c\u75c7\u4e2d\u7684\u201c\u5934\u53f7\u6740\u624b\u201d\u3002 \u6839\u636e\uff37\uff28\uff2f\u7684\u5206\u7c7b\uff0c\u80ba\u764c\u6309\u7167\u6cbb\u7597\uff0c\u9884\u540e\u53ca\u751f\u7269\u5b66\u7279\u5f81 […]<\/p>\n","protected":false},"author":1,"featured_media":25701,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[2],"tags":[],"_links":{"self":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/25700"}],"collection":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/comments?post=25700"}],"version-history":[{"count":1,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/25700\/revisions"}],"predecessor-version":[{"id":25725,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/25700\/revisions\/25725"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/media\/25701"}],"wp:attachment":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/media?parent=25700"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/categories?post=25700"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/tags?post=25700"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}