{"id":98392,"date":"2019-03-22T00:00:50","date_gmt":"2019-05-17T08:14:24","guid":{"rendered":"http:\/\/www.05921.net\/index.php\/98392\/"},"modified":"2019-05-17T16:14:27","modified_gmt":"2019-05-17T08:14:27","slug":"09931c3f91","status":"publish","type":"post","link":"https:\/\/www.05921.net\/index.php\/98392\/","title":{"rendered":"PD-1\/PD-L1 \u6297\u4f53\u4e34\u5e8a\u836f\u7406\u5b66\u7814\u7a76\u7684\u8003\u8651"},"content":{"rendered":"
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PD-1 \/PD-L1 \u6297\u4f53\u4e34\u5e8a\u836f\u7406\u5b66\u7814\u7a76\u7684\u8003\u8651<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

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Consideration on clinical pharmacological studies of <\/span><\/strong>anti-PD-1 and anti-PD-L1 antibodies<\/span><\/strong>
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\u4e2d\u56fd\u65b0\u836f\u6742\u5fd7\uff0c2018 \u5e74\u7b2c27 \u5377\u7b2c4 \u671f<\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

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\u674e\u5a1c\uff0c\u738b\u7389\u73e0\uff0c\u6768\u8fdb\u6ce2<\/p>\n

\u56fd\u5bb6\u98df\u54c1\u836f\u54c1\u76d1\u7763\u7ba1\u7406\u603b\u5c40\u836f\u54c1\u5ba1\u8bc4\u4e2d\u5fc3<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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PD-1 \/PD-L1 \u6297\u4f53\u662f\u4e00\u7c7b\u514d\u75ab\u68c0\u67e5\u70b9\u6291\u5236\u5242\uff0c\u53ef\u901a\u8fc7\u6291\u5236\u80bf\u7624\u514d\u75ab\u9003\u9038\uff0c\u91cd\u65b0\u6fc0\u6d3b\u514d\u75ab\u7cfb\u7edf\u653b\u51fb\u80bf\u7624\u7ec6\u80de\uff0c\u4ece\u800c\u8fbe\u5230\u6cbb\u7597\u80bf\u7624\u7684\u76ee\u7684\u3002<\/span><\/p>\n

\u968f\u7740PD-1 \/PD-L1 \u6297\u4f53\u7684\u4e34\u5e8a\u7814\u7a76\u548c\u5e94\u7528\u7684\u6df1\u5165\uff0c\u6211\u4eec\u5bf9\u8be5\u7c7b\u836f\u7269<\/span>\u7684\u8ba4\u8bc6\u6b63\u65e5\u8d8b\u5b8c\u5584\u3002\u672c\u6587\u4ecb\u7ecd\u5168\u7403\u4e0a\u5e02\u76845 \u79cdPD-1 \/PD-L1 \u6297\u4f53\u5728\u9996\u6b21\u83b7\u5f97FDA\uff0cEMA \u548cPMDA \u6279\u51c6\u65f6\u7528<\/span>\u4e8e\u652f\u6301\u6ce8\u518c\u7533\u8bf7\u7684\u4e3b\u8981\u4e34\u5e8a\u836f\u7406\u5b66\u7814\u7a76\u5185\u5bb9\uff0c\u4ee5\u53ca\u4e0a\u8ff0\u56fd\u5916\u76d1\u7ba1\u673a\u6784\u6279\u51c6\u7684\u4e3b\u8981\u4f9d\u636e\uff0c\u65e8\u5728\u4e3a\u6211\u56fd\u7684PD-1 \/<\/span>PD-L1 \u6297\u4f53\u7684\u7814\u53d1\u53ca\u65b0\u836f\u5ba1\u8bc4\u5de5\u4f5c\u63d0\u4f9b\u53c2\u8003\u3002<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u8fc7\u53bb\u51e0\u5e74\u4e2d\uff0c\u514d\u75ab\u6cbb\u7597\u5728\u80bf\u7624\u6cbb\u7597\u9886\u57df\u88ab\u5e7f\u6cdb\u5e94\u7528\uff0c\u662f\u7ee7\u624b\u672f\u3001\u653e\u7597\u3001\u5316\u7597\u53ca\u9776\u5411\u6cbb\u7597\u540e\uff0c\u53c8\u4e00\u4e2a\u5177<\/span>\u6709\u6f5c\u529b\u7684\u5168\u8eab\u6cbb\u7597\u65b9\u5f0f\uff3b1\uff3d\u3002<\/span><\/p>\n

\u5c24\u5176\u662f\u81ea\u80bf\u7624\u514d\u75ab\u6cbb<\/span>\u7597\u88ab\u8bc4\u4e3a\u201c2013 \u5e74\u5ea6\u79d1\u5b66\u7a81\u7834\u201d\u4ee5\u6765\uff0c\u514d\u75ab\u68c0\u67e5\u70b9\u7684<\/span>\u963b\u65ad\u7597\u6cd5\u5df2\u9010\u6e10\u6210\u4e3a\u80bf\u7624\u6cbb\u7597\u9886\u57df\u7684\u7126\u70b9\uff3b2\uff3d\u3002<\/span><\/p>\n

\u514d<\/span>\u75ab\u68c0\u67e5\u70b9\u662f\u4e00\u7c7b\u6b63\u5e38\u673a\u4f53\u5185\u5b58\u5728\u7684\u514d\u75ab\u6291\u5236\u4fe1\u53f7\u5206<\/span>\u5b50\uff0c\u901a\u8fc7\u8c03\u8282\u5171\u523a\u6fc0\u548c\u5171\u6291\u5236\u4fe1\u53f7\u7684\u5e73\u8861\u6765\u53d1\u6325\u514d<\/span>\u75ab\u8c03\u8282\u4f5c\u7528\uff0c\u800c\u5171\u523a\u6fc0\u548c\u5171\u6291\u5236\u4fe1\u53f7\u5728\u7ef4\u6301\u81ea\u8eab\u8010<\/span>\u53d7\u548c\u8c03\u8282T \u7ec6\u80de\u5e94\u7b54\u7684\u5e45\u5ea6\u4e0e\u6301\u7eed\u65f6\u95f4\u65b9\u9762\u5177\u6709<\/span>\u91cd\u8981\u4f5c\u7528\uff3b3\uff3d\u3002<\/span><\/p>\n

\u514d\u75ab\u68c0\u67e5\u70b9\u5206\u5b50\u7684\u8fc7\u8868\u8fbe\uff0c\u53ef\u80fd\u5728\u80bf<\/span>\u7624\u5fae\u73af\u5883\u4e2d\u8bf1\u5bfc\u514d\u75ab\u6291\u5236\uff0c\u8fdb\u800c\u5f15\u53d1\u80bf\u7624\u514d\u75ab\u9003<\/span>\u9038\uff3b4 \uff0d 5\uff3d\u3002<\/span><\/p>\n

\u963b\u65ad\u8fd9\u4e9b\u514d\u75ab\u68c0\u67e5\u70b9\uff0c\u5982\u7ec6\u80de\u6bd2T \u6dcb\u5df4\u7ec6<\/span>\u80de\u76f8\u5173\u6297\u539f4( cytotoxic T lymphocyte-associated antigen-<\/span>4\uff0cCTLA-4 ) \u3001\u7a0b\u5e8f\u6027\u6b7b\u4ea1\u53d7\u4f53-1 ( programmed <\/span>cell death receptor-1\uff0cPD-1) \u53ca\u7a0b\u5e8f\u6027\u6b7b\u4ea1\u53d7\u4f53\u914d\u4f53-<\/span>1( programmed cell death receptor-ligand 1\uff0cPD-L1) \uff0c<\/span><\/p>\n

\u53ef\u4ee5\u89e3\u9664\u80bf\u7624\u8bf1\u5bfc\u7684\u514d\u75ab\u6291\u5236\uff0c\u91cd\u65b0\u6fc0\u6d3b\u514d\u75ab\u7cfb\u7edf\u653b\u51fb\u80bf\u7624\u7ec6\u80de\uff0c\u8fbe\u5230\u6cbb\u7597\u80bf\u7624\u7684\u76ee\u7684\u3002<\/span><\/p>\n

\u65e5\u672c\u836f\u54c1\u533b\u7597\u5668\u68b0\u5c40( PMDA) \u548c\u7f8e\u56fd\u98df\u54c1\u836f\u54c1\u76d1\u7763\u7ba1\u7406\u5c40( FDA) \u57282014 \u5e74\u5206\u522b\u5148\u540e\u6279\u51c6\u4e86nivolumab(<\/span>\u7eb3\u6b66\u5355\u6297) \u548cpembrolizumab( \u6d3e\u59c6\u5355\u6297) \u7528<\/span>\u4e8e\u6cbb\u7597\u5bf9\u5176\u4ed6\u836f\u7269\u6cbb\u7597\u65e0\u6548\u7684\u665a\u671f\u6216\u65e0\u6cd5\u5207\u9664\u7684\u9ed1<\/span>\u8272\u7d20\u7624\u60a3\u8005\uff0c\u6210\u4e3a\u5168\u7403\u9996\u5148\u83b7\u6279\u76842 \u4e2aPD-1 \u514d\u75ab\u68c0<\/span>\u67e5\u70b9\u6291\u5236\u5242\u3002<\/span><\/p>\n

\u672c\u6587\u5bf9\u5168\u7403\u5df2\u4e0a\u5e02PD-1 \/PD-L1 \u6297\u4f53<\/span>\u5728\u9996\u6b21\u83b7\u6279\u65f6\u7528\u4e8e\u652f\u6301\u6ce8\u518c\u7533\u8bf7\u7684\u4e3b\u8981\u4e34\u5e8a\u836f\u7406\u5b66<\/span>\u7814\u7a76\u5185\u5bb9\uff0c\u4ee5\u53ca\u56fd\u9645\u5404\u76d1\u7ba1\u673a\u6784\u6279\u51c6\u7684\u4f9d\u636e\u8fdb\u884c\u4ecb<\/span>\u7ecd\u603b\u7ed3\uff0c\u4ee5\u671f\u4e3a\u6211\u56fd\u7684PD-1 \/PD-L1 \u6297\u4f53\u7684\u7814\u53d1\u53ca<\/span>\u65b0\u836f\u5ba1\u8bc4\u5de5\u4f5c\u63d0\u4f9b\u53c2\u8003\u3002<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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1<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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PD-1 \/PD-L1 \u6297\u4f53\u836f\u7269\u7684\u4f5c\u7528\u673a\u5236<\/strong><\/p>\n<\/section>\n<\/section>\n

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PD-1 \u5c5e\u4e8eB7-CD28 \u8d85\u5bb6\u65cf\u6210\u5458\u4e4b\u4e00\uff0c\u662f\u4e00\u79cd\u7ec6\u80de\u8868\u9762\u534f\u540c\u6291\u5236\u53d7\u4f53\uff0c\u8868\u8fbe\u4e8eT \u7ec6\u80de\u3001B \u7ec6\u80de\u3001\u81ea\u7136<\/span>\u6740\u4f24\u6027T \u7ec6\u80de\u3001\u6d3b\u5316\u7684\u5355\u6838\u7ec6\u80de\u548c\u6811\u7a81\u72b6\u7ec6\u80de( dendritic <\/span>cells\uff0cDCs) \uff3b6\uff3d\u3002<\/span><\/p>\n

\u76ee\u524dPD-1 \u7684\u4e3b\u8981\u914d\u4f53\u88ab\u8bc1\u5b9e<\/span>\u67092 \u4e2a: PD-L1( \u53c8\u79f0B7-H1 \u6216CD274) \u548cPD-L2( \u53c8<\/span>\u79f0B7-DC \u6216CD273) \uff0c\u4e24\u8005\u7684\u8868\u8fbe\u8c31\u4e0d\u540c\u3002<\/span><\/p>\n

PD-L2<\/span>\u4ec5\u8868\u8fbe\u4e8e\u6297\u539f\u63d0\u5448\u7ec6\u80de( antigen presenting cell\uff0c <\/span>APC) \u4e2d\uff0c\u5305\u62ecDCs; PD-L1 \u5728\u4eba\u4f53\u6b63\u5e38\u7ec4\u7ec7\u7ec6\u80de\u4e2d<\/span>\u8868\u8fbe\u91cf\u8f83\u5c11\uff0c\u9664\u4e86\u5728APC \u4e2d\u8868\u8fbe\u5916\uff0c\u4ec5\u5728\u5fc3\u810f\u5185\u76ae\u3001<\/span>\u5fae\u8840\u7ba1\u5185\u76ae\u7ec6\u80de\u3001\u80f0\u5c9b\u548c\u80ce\u76d8\u5408\u4f53\u6ecb\u517b\u7ec6\u80de\u4e2d\u5c11\u91cf<\/span>\u8868\u8fbe\uff3b7\uff3d\u3002<\/p>\n

\u4f46\u662f\uff0cPD-L1 \u86cb\u767d\u8fd8\u53ef\u5728\u591a\u79cd\u6076\u6027\u80bf\u7624\u7ec6\u80de\u7684\u7ec6\u80de\u819c\u4e0a\u5927\u91cf\u8868\u8fbe\uff3b8\uff3d\u3002<\/span><\/p>\n

PD-L1 \u88ab\u8ba4\u4e3a\u662fPD-1<\/span>\u4f9d\u8d56\u6027\u514d\u75ab\u6291\u5236\u7684\u4e3b\u8981\u4ecb\u8d28\uff3b9\uff3d\u3002<\/span><\/p>\n

\u5728\u80bf\u7624\u5c40\u90e8\u5fae\u73af<\/span>\u5883\u4e2d\uff0cPD-1 \u4e0e\u5176\u914d\u4f53\u76f8\u7ed3\u5408\u53ef\u6fc0PD-1 \/PD-L1 \u4fe1<\/span>\u53f7\u901a\u8def\uff0c\u6291\u5236\u80bf\u7624\u7279\u5f02\u6027T \u7ec6\u80de\u589e\u6b96\u3001\u6d3b\u5316\u548c\u5206\u6ccc<\/span>\u7ec6\u80de\u56e0\u5b50\uff0c\u4fc3\u8fdb\u80bf\u7624\u751f\u957f\u3002<\/span><\/p>\n

\u9488\u5bf9\u4e0a\u8ff0\u673a\u5236\u7814\u53d1\u7684\u7279\u5f02\u6027\u6297\u4f53\u901a\u8fc7\u963b\u65adPD-1 \u4e0ePD-L1 \u7ed3\u5408\uff0c\u4ece\u800c\u963b\u65adPD-1 \/PD-L1 \u4fe1\u53f7\u901a\u8def\uff0c<\/span>\u89e3\u9664\u673a\u4f53\u7684\u514d\u75ab\u6291\u5236\uff0c\u6062\u590dT \u7ec6\u80de\u7684\u6297\u80bf\u7624\u6d3b\u6027\u3002<\/span><\/p>\n

\u76ee\u524d\u7528\u4e8e\u963b\u65adPD-1 \/PD-L1 \u4fe1\u53f7\u901a\u8def\u7684\u6297\u4f53\u5927\u81f4\u53ef\u52062 \u7c7b: PD-1 \u6297\u4f53\u548cPD-L1 \u6297\u4f53\u3002<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u56fd\u9645\u4e0aPD-1 \/PD-L1 \u6297\u4f53\u836f\u7269\u7684\u6279\u51c6\u60c5\u51b5<\/strong><\/p>\n<\/section>\n<\/section>\n

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\u622a\u81f32017 \u5e746 \u6708\uff0c\u5168\u7403\u5df2\u6279\u51c6\u4e0a\u5e02\u7684PD-1 \/PD-L1 \u6297\u4f53\u5171\u67095 \u4e2a( \u89c1\u88681) \u3002<\/span><\/p>\n

\"PD-1\/PD-L1<\/p>\n

\u5176\u4e2d\uff0cnivolumab \u5206<\/span>\u522b\u4e8e2014 \u5e747 \u6708\u30012014 \u5e7412 \u6708\u548c2015 \u5e747 \u6708\u5728\u65e5<\/span>\u672c\u3001\u7f8e\u56fd\u548c\u6b27\u76df\u83b7\u6279\u4e0a\u5e02\uff0c\u4f46\u7531\u4e8e\u5546\u4e1a\u539f\u56e0\uff0c\u8be5\u54c1\u5df2<\/span>\u4e8e2015 \u5e7411 \u6708\u5728\u6b27\u76df\u64a4\u5e02\uff3b10\uff3d; pembrolizumab \u5206\u522b<\/span>\u4e8e2014 \u5e749 \u6708\u30012015 \u5e747 \u6708\u548c2016 \u5e749 \u6708\u83b7\u5f97\u7f8e<\/span>\u56fd\u3001\u6b27\u76df\u548c\u65e5\u672c\u6279\u51c6\u4e0a\u5e02; atezolizumab ( \u963f\u66ff\u73e0\u5355<\/span>\u6297) \u3001avelumab( \u963f\u7ef4\u9c81\u5355\u6297) \u548cdurvalumab( \u5ea6\u4f10\u9c81<\/span>\u5355\u6297) \u5219\u4ec5\u5728\u7f8e\u56fd\u83b7\u6279\u4e0a\u5e02\u3002<\/span><\/p>\n

PD-1 \/PD-L1 \u6297\u4f53\u7684\u4e34<\/span>\u5e8a\u9002\u5e94\u8bc1\u5df2\u8986\u76d6\u4e86\u975e\u5c0f\u7ec6\u80de\u80ba\u764c\u3001\u5934\u9888\u90e8\u9cde\u72b6\u7ec6\u80de<\/span>\u764c\u3001\u970d\u5947\u91d1\u6dcb\u5df4\u7624\u3001\u5c3f\u8def\u4e0a\u76ae\u764c\u7b49\u591a\u79cd\u5b9e\u4f53\u7624\u7684\u6cbb<\/span>\u7597\u3002<\/span><\/p>\n

\u503c\u5f97\u4e00\u63d0\u7684\u662f\uff0c\u9664\u4e86\u57fa\u4e8e\u80bf\u7624\u539f\u53d1\u90e8\u4f4d\u7684\u5404\u7c7b<\/span>\u9002\u5e94\u8bc1\u4e4b\u5916\uff0cFDA \u8fd8\u4e8e2017 \u5e745 \u6708\u6279\u51c6\u4e86pembrolizumab<\/span>\u589e\u52a0\u65b0\u9002\u5e94\u8bc1\u7684\u8865\u5145\u7533\u8bf7\uff3b11\uff3d\uff0c\u5373\u8be5\u836f\u53ef\u7528\u4e8e<\/span>\u5e26\u6709\u201c\u9ad8\u5ea6\u5fae\u536b\u661f\u4e0d\u7a33\u5b9a\u6027( microsatellite instabilityhigh\uff0c<\/span>MSI-H) \u6216\u9519\u914d\u4fee\u590d\u7f3a\u9677( mismatch repair deficient\uff0c<\/span>dMM\uff32) \u201d\u7684\u6210\u4eba\u6216\u513f\u7ae5\u4e0d\u53ef\u5207\u9664\u6216\u8f6c\u79fb\u6027\u5b9e<\/span>\u4f53\u7624\u60a3\u8005\u7684\u6cbb\u7597\u3002\u8fd9\u662fFDA \u7b2c\u4e00\u6b21\u57fa\u4e8e\u751f\u7269\u6807\u5fd7<\/span>\u7269( biomarker) \u6279\u51c6\u836f\u54c1\uff0c\u5373\u4e3a\u6297\u80bf\u7624\u836f\u7269\u83b7\u6279\u5386\u53f2<\/span>\u4e0a\u7684\u4e00\u4e2a\u91cd\u8981\u91cc\u7a0b\u7891\u3002<\/span><\/p>\n

\u5168\u7403\u5f00\u5c55\u7684PD-1 \/PD-L1 \u6297\u4f53\u7684\u4e34\u5e8a\u8bd5\u9a8c\u7ea6\u6709700 \u9879\uff3b14\uff3d\u3002<\/span><\/p>\n

\u76ee\u524d\u6211\u56fd\u867d\u7136\u5c1a\u65e0PD-1 \/PD-L1 \u6297<\/span>\u4f53\u83b7\u51c6\u4e0a\u5e02\uff0c\u4f46\u4e0d\u5c11\u65b0\u836f\u5df2\u8fdb\u5165\u4e86\u4e34\u5e8a\u8bd5\u9a8c\u9636<\/span>\u6bb5\uff3b15\uff3d\uff0c\u5168\u7403\u5f00\u5c55\u7684\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\u7ea660 \u591a\u9879\u5728\u4e2d\u56fd\u5883<\/span>\u5185\u8fdb\u884c\u3002<\/span><\/p>\n

2016 \u5e741 \u6708\u4ee5\u6765\u56fd\u5185\u591a\u5bb6\u4f01\u4e1a\u9646\u7eed\u83b7<\/span>\u5f97\u4e86PD-1 \u6297\u4f53\u7684\u4e34\u5e8a\u8bd5\u9a8c\u6279\u4ef6\uff0c\u8fd9\u4e5f\u6807\u5fd7\u7740\u6211<\/span>\u56fd\u751f\u7269\u6280\u672f\u836f\u7269\u7684\u7814\u53d1\u6b63\u5728\u7f29\u5c0f\u4e0e\u56fd\u9645\u9ad8\u6c34\u5e73<\/span>\u7684\u5dee\u8ddd\u3002<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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2<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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3. PD-1 \/PD-L1 \u6297\u4f53\u836f\u7269\u7528\u4e8e\u4e0a\u5e02\u6ce8\u518c\u7533\u8bf7\u7684\u4e34<\/strong>\u5e8a\u836f\u7406\u5b66\u7814\u7a76\u5185\u5bb9<\/strong><\/p>\n<\/section>\n<\/section>\n

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\u4ee55 \u79cd\u5df2\u4e0a\u5e02PD-1 \/PD-L1 \u6297\u4f53\u5728FDA\u3001\u6b27\u76df\u836f\u54c1\u7ba1\u7406\u5c40( EMA) \u3001PMDA \u7b49\u56fd\u9645\u76d1\u7ba1\u673a\u6784\u9996\u6b21\u83b7<\/span>\u6279\u65f6\uff0c\u5404\u673a\u6784\u516c\u5f00\u7684\u5ba1\u8bc4\u62a5\u544a\u4e3a\u57fa\u7840\uff0c\u5bf9\u652f\u6301\u6ce8\u518c\u7533<\/span>\u8bf7\u7684\u4e3b\u8981\u4e34\u5e8a\u836f\u7406\u5b66\u5185\u5bb9\u8fdb\u884c\u4ecb\u7ecd\u603b\u7ed3\uff0c\u4ee5\u53ca\u5bf9\u56fd<\/span>\u9645\u5404\u76d1\u7ba1\u673a\u6784\u6279\u51c6\u7684\u4f9d\u636e\u8fdb\u884c\u8ba8\u8bba\u3002<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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3.1 nivolumab<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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3.1.1 PMDA \u5ba1\u8bc4\u62a5\u544a\uff3b16\uff3d <\/strong><\/p>\n

\u7533\u8bf7\u4eba\u63d0\u4ea4\u4e86ONO-4538-01\uff0cONO-4538-02\uff0cCA209001 \u548cCA209003 \u7b494<\/span>\u9879\u4e34\u5e8a\u7814\u7a76\uff0c\u5176\u4e2d\u524d2 \u9879\u5206\u522b\u4e3a2009 \u5e74\u548c2011 \u5e74<\/span>\u65e5\u672c\u5883\u5185\u5f00\u5c55\u7684\u2160\uff0c\u2161\u671f\u4e34\u5e8a\u8bd5\u9a8c\uff0c\u540e2 \u9879\u4e3a2006\u5e74\u548c2008 \u5e74\u5728\u7f8e\u56fd\u5f00\u5c55\u7684\u2160\u671f\u4e34\u5e8a\u8bd5\u9a8c\u3002<\/span><\/p>\n

PMDA<\/span>\u6279\u51c6\u8be5\u7533\u8bf7\u4e3b\u8981\u662f\u57fa\u4e8e\u2161\u671fONO-4538-02 \u7814\u7a76\u7684<\/span>\u7ed3\u679c\uff0c\u6279\u51c6\u7684\u7528\u6cd5\u7528\u91cf\u4e3a2 mg\u00b7kg\u22121<\/span><\/sup>\uff0c\u6bcf3 \u5468\u7ed9\u836f1<\/span>\u6b21( Q3W) \uff0c\u9759\u8109\u8f93\u6ce8\u7ed9\u836f\uff0c\u4f46\u7531\u4e8e\u4e34\u5e8a\u8bd5\u9a8c\u7eb3\u5165\u7684<\/span>\u65e5\u672c\u53d7\u8bd5\u8005\u5f88\u5c11( \u517152 \u4f8b) \uff0c\u6240\u4ee5\u5728\u65e5\u672c\u4e0a\u5e02\u65f6\u4e3a<\/span>\u201c\u6709\u6761\u4ef6\u6279\u51c6\u201d\uff0c\u5373\u8981\u6c42\u4e0a\u5e02\u540e\u7533\u8bf7\u4eba\u5bf9\u6240\u6709\u60a3\u8005\u7684<\/span><\/p>\n

\u7528\u836f\u7ed3\u679c\u8fdb\u884c\u76d1\u6d4b\u8c03\u67e5\uff0c\u76f4\u81f3\u60a3\u8005\u8fbe\u5230\u4e00\u5b9a\u7d2f\u79ef\u6570\u91cf\uff0c\u4ee5\u4fbf\u4e86\u89e3\u60a3\u8005\u4f7f\u7528\u8be5\u4ea7\u54c1\u6cbb\u7597\u7684\u7279\u70b9\uff0c\u5e76\u5728\u4e0a\u5e02<\/span>\u65e9\u671f\u6536\u96c6\u4ea7\u54c1\u5b89\u5168\u6027\u548c\u6709\u6548\u6027\u6570\u636e\uff0c\u4ece\u800c\u53ef\u4ee5\u91c7\u53d6<\/span>\u5fc5\u8981\u63aa\u65bd\u6765\u786e\u4fdd\u4ea7\u54c1\u5408\u7406\u4f7f\u7528\u3002<\/span><\/p>\n

ONO-4538-01 \u7814\u7a76\u7eb3\u5165\u4e8617 \u4f8b\u665a\u671f\u5b9e\u4f53\u7624\u60a3\u8005\uff0c\u5355\u6b21\u9012\u589e\u5242\u91cf1 \uff5e 20 mg\u00b7kg<\/span>\u22121<\/sup><\/span>\uff0c\u836f\u65f6\u66f2\u7ebf\u4e0b\u9762\u79ef( area under the curve\uff0cAUClast) \u4e0e\u5242\u91cf\u5448\u6bd4\u4f8b\u589e\u52a0;\u5cf0\u6d53\u5ea6( Cmax) \u4ec5\u57281 \uff5e 10 mg\u00b7kg\u22121<\/span><\/sup> \u5242\u91cf\u8303\u56f4\u5185\u5448\u6bd4\u4f8b\u589e\u52a0\uff0c\u572810 \uff5e 20 mg\u00b7kg \u22121<\/span><\/sup> \u5242\u91cf\u8303\u56f4\u5219\u5c0f\u4e8e\u5242\u91cf\u589e\u52a0\u7684\u6bd4\u4f8b( \u7533\u8bf7\u4eba\u89e3\u91ca\u8be5\u8d8b\u52bf\u662f\u7531\u4e8e\u5728\u6700\u9ad8\u5242\u91cf\u7ec4<\/span>\u7684Cmax\u503c\u6709\u4e2a\u4f53\u95f4\u53d8\u5f02\uff0cn = 3) \u3002<\/span><\/p>\n

nivolumab \u7684\u8fbe\u5cf0<\/span>\u65f6\u95f4( Tmax<\/span>) \u7ea6\u4e3a1 \uff5e 9 h\uff0c\u534a\u8870\u671f( t1 \/2<\/span>) \u4e0e\u5185\u6e90\u6027IgG4<\/span>\u76f8\u8fd1( 504 h) \uff0c\u7a33\u6001\u8868\u89c2\u5206\u5e03\u5bb9\u79ef( volume of distribution <\/span>at steady-state\uff0cVss) \u51e0\u4e4e\u4e0e\u4eba\u4f53\u8840\u6d46\u5bb9\u91cf\u76f8\u8fd1<\/span>( \u7ea6\u4e3a50 mL\u00b7kg\u22121<\/span><\/sup> ) \uff0c\u6e05\u9664\u7387( clearance\uff0cCL) \u548cVss\u4e0e<\/span>\u5242\u91cf\u65e0\u5173( \u89c1\u88682) \u3002<\/span><\/p>\n

\"PD-1\/PD-L1<\/p>\n

CA209001 \u7814\u7a76\u7eb3\u5165\u4e8639 \u4f8b\u665a<\/span>\u671f\u6216\u590d\u53d1\u7684\u5b9e\u4f53\u7624\u60a3\u8005\uff0c\u5355\u6b21\u7ed9\u836f\u5242\u91cf0. 3 \uff5e 10<\/span>mg\u00b7kg\u22121<\/span><\/sup>\u8303\u56f4\u5185\uff0cAUCinf<\/span>\u548cCmax\u4e0e\u5242\u91cf\u5448\u6bd4\u4f8b\u589e\u52a0\u3002<\/span><\/p>\n

Tmax\uff0ct<\/span>1 \/2<\/span>\uff0cCL \u548cVss<\/span>\u7b49\u53c2\u6570\u4e0eONO-4538-01 \u7814\u7a76\u7ed3\u679c<\/span>\u8f83\u76f8\u8fd1\u3002CA209003 \u7814\u7a76\u7684306 \u4f8b\u5b9e\u4f53\u7624\u60a3\u8005\uff0c0.<\/span>1 \uff5e<\/span>10 mg\u00b7kg\u22121<\/span><\/sup> \u5242\u91cf\u6bcf2 \u5468\u7ed9\u836f1 \u6b21( Q2W) \uff0c\u5171\u7ed9\u836f8<\/span>\u5468\u3002\u5728\u7b2c1 \uff5e 3 \u5468\u671f\uff0cCmax<\/span>\u548cAUCtau<\/span>\u4e0e\u5242\u91cf\u5448\u6b63\u6bd4\uff0c<\/span>Cmax<\/span>\u548cAUCtau<\/span>\u7684\u7d2f\u79ef\u6307\u6570\u5206\u522b\u4e3a2. 0 \uff5e 2. 4 \u548c2.9 \uff5e<\/span>3.3\uff0c\u4e0d\u968f\u5242\u91cf\u53d8\u5316\u3002<\/span><\/p>\n

ONO-4538-02 \u662f\u9488\u5bf9\u665a\u671f\u6216\u590d\u53d1\u4e14\u4e0d\u53ef\u5207\u9664\u7684\u6076\u6027\u9ed1\u8272\u7d20\u7624\u60a3\u8005\u7684\u2161\u671f\u4e34\u5e8a\u7814\u7a76\uff0c\u7eb3\u516535 \u4f8b\u60a3<\/span>\u8005\uff0c2<\/span>mg\u00b7kg\u22121<\/span><\/sup>\uff0cQ3W \u8fde\u7eed\u7ed9\u836f18 \u5468\u540e\uff0c\u8840\u6e05\u836f\u7269\u6d53<\/span>\u5ea6\u4e3a44.3 \uff5e 51.6 \u03bcg\u00b7mL\u22121<\/span><\/sup> ( \u7b2c18 \u5468\u7ed9\u836f\u524d\u5df2\u8fbe\u5230<\/span>\u7a33\u6001) \u3002<\/span><\/p>\n

\u7814\u7a76\u8bc4\u4f30\u8ba4\u4e3a2 mg\u00b7kg\u22121<\/span><\/sup>\uff0cQ3W \u5242\u91cf\u7684nivolumab<\/span>\u4e0d\u4f1a\u5f71\u54cdQT \/QTc<\/span>\u95f4\u671f\u3002<\/span><\/p>\n

\u6b64\u5916\uff0c\u7533\u8bf7\u4eba\u8fd8\u63d0\u4ea4\u4e86\u4e00\u9879\u57fa\u4e8e\u4e0a\u8ff04 \u9879\u7814\u7a76\u7684\u7fa4\u4f53PK \u5206\u6790\uff0c\u8ba4\u4e3a\u4e2d\u592e\u5ba4\u5206\u5e03\u5bb9\u79ef( V1<\/span>) \u968f\u4f53\u91cd<\/span>\u589e\u52a0\u800c\u5347\u9ad8\uff0c\u8fd9\u53ef\u80fd\u7531\u4e8enivolumab \u4e3b\u8981\u5206\u5e03\u4e8e\u5faa\u73af<\/span>\u8840\u6db2\u4e2d\u3002<\/span><\/p>\n

\u7fa4\u4f53PK \u6a21\u578b\u8fd8\u6a21\u62df\u4f30\u8ba1\u4e863 \u5468\u7a33\u6001\u7684<\/span>AUC( \u5242\u91cf2 mg\u00b7kg\u22121<\/span><\/sup>\uff0cQ3W) \u4e3a15 204 \u03bcg\u00b7h\u00b7mL\u22121<\/span><\/sup>\u3002<\/span><\/p>\n

\u4e0a\u8ff04 \u9879\u7814\u7a76\uff0c\u81f3\u5c11\u6d4b\u5b9a\u8fc71 \u6b21\u7684\u8840\u6e05\u4e2d\u6297\u836f\u6027\u6297\u4f53( anti-drug antibody\uff0cADA) \u6c34\u5e73\u57280 \uff5e 11. 8%\uff0c\u6301<\/span>\u7eed\u9633\u6027\u7387( \u8fde\u7eed2 \u6b21\u6d4b\u5b9a\u4e14\u6297\u4f53\u6ef4\u5ea6\u2265\u7ed9\u836f\u524d\u6297\u4f53<\/span>\u6ef4\u5ea6\u76844 \u500d) \u7ea6\u4e3a0 \uff5e 0. 8%\u3002\u57fa\u4e8e\u5206\u6790\u7ed3\u679c\uff0cADA<\/span>\u5bf9nivolumab \u7684PK \u6ca1\u6709\u663e\u8457\u5f71\u54cd\u3002<\/span><\/p>\n

3.1.2 FDA \u5ba1\u8bc4\u62a5\u544a\uff3b17\uff3d <\/strong><\/p>\n

nivolumab \u5728FDA \u7528\u4e8e\u652f\u6301\u6ce8\u518c\u7533\u8bf7\u7684\u6709\u6548\u6027\u3001\u5b89\u5168\u6027\u3001PK \u53ca\u514d\u75ab\u539f\u6027\u6570<\/span>\u636e\uff0c\u662f\u57fa\u4e8e0.1 \uff5e 20 mg\u00b7kg\u22121<\/span><\/sup>\u5242\u91cf\u8303\u56f4\u7ed9\u836f\u7684\u591a\u9879\u7814<\/span>\u7a76( \u6db5\u76d6\u4e86PMDA \u5ba1\u8bc4\u62a5\u544a\u4e2d\u63d0\u4ea4\u76844 \u9879\u7814\u7a76\uff0c\u4ee5<\/span>\u53caCA209009\uff0cCA209010\uff0cCA209063 \u548cCA209037 \u7b49<\/span>\u7814\u7a76) \uff0c\u5176\u4e2dCA209037 \u7684\u7814\u7a76\u7ed3\u679c\u652f\u6301\u8be5\u54c1\u7684\u7528\u6cd5<\/span>\u7528\u91cf\u4e3a3 mg\u00b7kg\u22121<\/span><\/sup>\uff0cQ2W\u3002<\/span><\/p>\n

\u6bcf2 \u5468\u6216\u6bcf3 \u54681 \u6b21\uff0c\u5355\u6b21\u6216\u591a\u6b21\u63a5\u53d7\u7528\u836f\u7684909 \u4f8b\u60a3\u8005\u7684\u7fa4\u4f53PK \u6570\u636e\u663e\u793a\uff0cnivolumab \u7684CL<\/span>\u4e3a9.5 mL\u00b7h\u22121<\/span><\/sup>\uff0cVss<\/span>\u4e3a8. 0 L\uff0ct1 \/2<\/span><\/p>\n

\u4e3a26.7 d\uff0c\u7ed9\u836f12\u5468\u540e\u53ef\u8fbe\u5230\u7a33\u6001\u6d53\u5ea6\uff0c\u7cfb\u7edf\u7d2f\u79ef\u91cf\u7ea6\u4e3a3 \u500d\u3002\u76f8<\/span>\u5173\u9002\u5e94\u8bc1\u60a3\u8005\u4eba\u7fa4\u5728\u6b64\u7528\u6cd5\u7528\u91cf\u4e0b\uff0c\u66b4\u9732\u91cf-\u6548\u5e94<\/span>\u5173\u7cfb\u660e\u663e\u5448\u6c34\u5e73\u6027\u3002\u5e74\u9f84\u3001\u6027\u522b\u3001\u79cd\u65cf\u3001LDH \u57fa\u7ebf<\/span>\u503c\u3001PD-L1 \u8868\u8fbe\u91cf\u3001ADA \u751f\u6210\u3001\u80be\u635f\u4f24\u3001\u8f7b\u5ea6\u809d\u635f<\/span>\u4f24\u3001\u80bf\u7624\u7c7b\u578b\u548c\u5927\u5c0f\u7b49\u56e0\u7d20\uff0c\u5bf9nivolumab \u7684\u6e05\u9664<\/span>\u7387\u6ca1\u6709\u663e\u8457\u5f71\u54cd\u3002<\/span><\/p>\n

\u514d\u75ab\u539f\u6027\u5206\u6790\u663e\u793a\uff0c\u63a5\u53d7\u8fc7nivolumab \u6cbb\u7597\u7684\u60a3\u8005\u4e2d\u67098.5%( 24 \/281) \u4ea7\u751fADA\uff0c\u5176\u4e2d\u67092 \u4f8b\u60a3\u8005<\/span>\u4ea7\u751f\u4e2d\u548c\u6297\u4f53( 0.7%) \u3002<\/span><\/p>\n

3.1.3 EMA \u5ba1\u8bc4\u62a5\u544a\uff3b18\uff3d <\/strong><\/p>\n

nivolumab \u5728EMA \u63d0\u4ea4\u7684\u4e34\u5e8a\u836f\u52a8\u5b66\u7814\u7a76\u6570\u636e\uff0c\u4e0e\u63d0\u4ea4PMDA \u548cFDA \u7684\u57fa<\/span>\u672c\u4e00\u81f4\u3002<\/span><\/p>\n

\u9664\u4e0a\u8ff0\u6570\u636e\u4e4b\u5916\uff0c\u8be5\u62a5\u544a\u4e2d\u8fd8\u8bc4\u4f30\u4e86\u83b7\u5f97<\/span>\u7684\u4e34\u5e8a\u836f\u6548\u5b66\u6570\u636e\uff0c\u5728MDX1106-03( \u5373CA209003)<\/span>\u548cCA209009 \u7814\u7a76\u4e2d\uff0c\u5bf9PD-1 \u53d7\u4f53\u5360\u4f4d( receptor occupancy\uff0c<\/span>\uff32O) \u3001\u5916\u5468\u514d\u75ab\u7ec6\u80de\u7fa4\u8c03\u8282\u3001\u7cfb\u7edf\u6027\u7ec6\u80de\u56e0<\/span>\u5b50\u8c03\u8282\u3001\u7edd\u5bf9\u6dcb\u5df4\u7ec6\u80de\u6570( absolute lymphocyte count\uff0c<\/span>ALC) \u53d8\u5316\u7b49\u8fdb\u884c\u4e86\u5206\u6790\u3002\u7ed3\u679c\u663e\u793a\uff0c\u5728\u5927\u4e8e0.3<\/span>mg\u00b7kg \uff0d 1\u5242\u91cf\u65f6\uff0c\u5916\u5468\u8840PD-1 \u7684\uff32O \u8fbe\u5230\u9971\u548c\uff0c\u4e14\u6240<\/span>\u6709\u5242\u91cf\u7ec4\u7528\u836f1 h \u540e\uff32O \u5373\u8fbe\u523090% \u4ee5\u4e0a; \u6cbb\u7597\u7528<\/span>\u836f\u540e\u7684\u5916\u5468\u8840\u4e2d\uff0c\u6d3b\u5316\u7684T \u7ec6\u80de\u548cALC \u5747\u65e0\u4e34\u5e8a\u76f8<\/span>\u5173\u6539\u53d8; \u5728MDX1106-03 \u7814\u7a76\u4e2d\uff0cPD-L1 \u5728\u80bf\u7624\u4e2d\u7684<\/span>\u8868\u8fbe\u4e0e\u7597\u6548\u5e94\u7b54\u6ca1\u6709\u76f8\u5173\u6027\uff0cPD-L1 \u548cPD-L2 \u4f5c\u4e3a<\/span>Biomarker \u9884\u6d4bnivolumab \u7597\u6548\u7684\u610f\u4e49\u8fd8\u9700\u8fdb\u4e00\u6b65<\/span>\u7814\u7a76\u3002<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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3.2 pembrolizumab<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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3. 2.1 FDA \u5ba1\u8bc4\u62a5\u544a\uff3b19\uff3d <\/strong><\/p>\n

pembrolizumab \u5728FDA\u7528\u4e8e\u652f\u6301\u6ce8\u518c\u7533\u8bf7\u7684\u6709\u6548\u6027\u3001\u5b89\u5168\u6027\u3001PK \u53ca\u514d\u75ab\u539f<\/span>\u6027\u6570\u636e\uff0c\u662f\u57fa\u4e8e\u4e00\u9879\u5305\u542b\u4e86\u591a\u4e2a\u5b50\u7814\u7a76\u961f\u5217\u7684Study <\/span>P001 \u4e34\u5e8a\u7814\u7a76\uff0c\u5176\u4e2dB2 \u5b50\u7814\u7a76( \u4e00\u98791\u2236 1\u968f\u673a\u7684\u4f0a<\/span>\u5339\u5355\u6297\u96be\u6cbb\u6027\u9ed1\u8272\u7d20\u7624\u7684\u6709\u6548\u6027\u548c\u5b89\u5168\u6027\u7814\u7a76\uff0c173<\/span>\u4f8b) \u7684\u7ed3\u679c\u652f\u6301\u4e0a\u5e02\u7533\u8bf7\u3002<\/span><\/p>\n

\u5206\u522b\u7528\u4e862 \u79cd\u4e0d\u540c\u6280\u672f<\/span>\u7684\u836f\u52a8\u5b66\/\u836f\u6548\u5b66( pharmacokinetics and pharmacodynamics\uff0c<\/span>PK\/PD) \u8bc4\u4f30\u65b9\u6cd5\u6765\u786e\u5b9a\u5242\u91cf\u9009\u62e9\uff0c\u8ba4\u4e3a\u53ef<\/span>\u80fd\u6709\u4e34\u5e8a\u83b7\u76ca\u7684\u6700\u4f4e\u5242\u91cf\u4e3a1 \uff5e 2 mg\u00b7kg \u22121<\/span><\/sup>\uff0cQ3W\uff0c\u5e76\u4e14\u6700\u7ec8\u786e\u5b9a\u7ed9\u836f\u65b9\u5f0f\u4e3a2 mg\u00b7kg \u22121<\/span><\/sup>\uff0cQ3W\u3002<\/span><\/p>\n

pembrolizumab \u7ed9\u836f\u5242\u91cf\u4e3a1 \uff5e 10 mg\u00b7kg\u22121<\/span><\/sup>\uff0c<\/span>Q2W \u6216Q3W \u7684476 \u4f8b\u60a3\u8005\u7fa4\u4f53PK \u5206\u6790\u7ed3\u679c\u663e\u793a\uff0c<\/span>\u8fbe\u5230\u836f\u7269\u7a33\u6001\u6d53\u5ea6\u7684\u65f6\u95f4\u7ea6\u4e3a18 \u5468\uff0ct 1 \/2<\/span>\u7ea6\u4e3a25.8 d\uff0c<\/span>Vss<\/span>\u4e3a7. 66 L\uff0cCL \u4e3a0. 22 L\u00b7d\u22121<\/span><\/sup>\u3002<\/span><\/p>\n

Q3W \u7ed9\u836f\u65f6\u7684\u7d2f<\/span>\u79ef\u6307\u6570\u7ea6\u4e3a2.1 \u500d\uff0c\u4e14\u5927\u591a\u6570( \uff5e 82%) \u7684\u7d2f\u79ef\u4f5c\u7528<\/span>\u53d1\u751f\u5728\u7b2c3 \u6b21\u7ed9\u836f\u540e\u3002<\/span><\/p>\n

2 \uff5e 10 mg\u00b7kg\u22121<\/span><\/sup> \u5242\u91cf\u8303\u56f4\u5185\uff0c<\/span>AUC \u7684\u589e\u52a0\u5448\u5242\u91cf\u4f9d\u8d56\u6027\u3002\u5e74\u9f84\u3001\u6027\u522b\u3001\u80bf\u7624\u5927\u5c0f\u3001<\/span>\u80be\u529f\u80fd\u635f\u4f24\u3001\u8f7b\u5ea6\u809d\u529f\u80fd\u635f\u4f24\u7b49\u591a\u79cd\u56e0\u7d20\uff0c\u5bf9pembrolizumab<\/span>\u7684\u66b4\u9732\u91cf\u6ca1\u6709\u663e\u8457\u5f71\u54cd\uff0c\u8be5\u7814\u7a76\u4e2d\u975e\u767d<\/span>\u79cd\u4eba\u7fa4\u6570\u636e\u8f83\u5c11\uff0c\u6240\u4ee5\u672a\u8bc4\u4f30\u79cd\u65cf\u56e0\u7d20\u5f71\u54cd\u3002<\/p>\n

\u4e34\u5e8a\u836f\u6548\u5b66\u5206\u6790\u663e\u793a\uff0c\u5242\u91cf\u4e3a2 \u621610 mg\u00b7kg\u22121<\/span><\/sup>\uff0c<\/span>Q3W \u65f6\uff0cpembrolizumab \u7684\u66b4\u9732\u91cf-\u6548\u5e94\u5173\u7cfb\u660e\u663e\u5448<\/span>\u6c34\u5e73\u6027\u3002<\/span><\/p>\n

\u7ed9\u836f\u5242\u91cf\u8fbe\u523010 mg\u00b7kg\u22121<\/span><\/sup>\uff0cQ3W \u65f6QTc<\/span>\u95f4<\/span>\u671f\u6ca1\u6709\u592a\u5927\u53d8\u5316( \u6570\u636e\u672a\u4e0e\u9633\u6027\u5bf9\u7167\u7ec4\u6bd4\u8f83) \u3002<\/span><\/p>\n

\u514d\u75ab\u539f\u6027\u5206\u6790\u663e\u793a\uff0c\u6240\u6709129 \u4f8b\u63a5\u53d7\u6cbb\u7597( 1 \uff5e<\/span>10 mg\u00b7kg\u22121<\/span><\/sup>\uff0cQ2W \u6216Q3W) \u7684\u60a3\u8005\u53ef\u68c0\u6d4b\u5230pembrolizumab<\/span>\u6d53\u5ea6\uff0c\u5176\u4e2d\u53ea\u67091 \u4f8b\u60a3\u8005\u56e0\u6cbb\u7597\u51fa\u73b0\u4e86<\/span>ADA \u9633\u6027\uff0c\u8fdb\u4e00\u6b65\u68c0\u6d4b\u786e\u8ba4\u4e3a\u4e2d\u548c\u6297\u4f53\uff0c\u4f46\u672a\u89c2\u6d4b<\/span>\u5230\u5bf9\u836f\u7269\u66b4\u9732\u6c34\u5e73\u7684\u5f71\u54cd\u3002<\/span><\/p>\n

3.2.2 EMA \u5ba1\u8bc4\u62a5\u544a\uff3b20\uff3d <\/strong><\/p>\n

pembrolizumab \u5728EMA\u63d0\u4ea4\u7684\u4e34\u5e8a\u836f\u7406\u5b66\u7814\u7a76\u6570\u636e\u4e5f\u662f\u57fa\u4e8eStudy P001 \u7684<\/span>\u4e34\u5e8a\u7814\u7a76\uff0c\u540c\u65f6\u63d0\u4ea4\u4e86\u4e00\u9879\u66f4\u65b0\u7684P001( \u622a\u81f32014<\/span>\u5e744\u6708) \u548cP002( \u622a\u81f32014 \u5e745 \u6708) \u7814\u7a76\u6df7\u5408\u6570\u636e<\/span>\u96c6\u7684\u6269\u5c55\u6027\u7ed3\u679c\uff0c\u5404PK \u53c2\u6570\u4ecd\u4e0e\u521d\u59cbP001 \u7814\u7a76\u6240<\/span>\u5f97\u6570\u636e\u57fa\u672c\u76f8\u8fd1\u3002<\/span><\/p>\n

\u540c\u65f6\uff0c\u4e34\u5e8a\u836f\u6548\u5b66\u8fd8\u63d0\u4f9b\u4e86Study<\/span>PD002 \u7684\u6570\u636e\uff0c\u901a\u8fc7\u89c2\u5bdf\u5916\u5468\u8840\u4f53\u5916T \u7ec6\u80de\u6d3b\u5316\u3001\u7ec6<\/span>\u80de\u56e0\u5b50\u4ea7\u751f\u7684\u60c5\u51b5\uff0c\u5bf9\u5065\u5eb7\u4eba\u548c\u764c\u75c7\u60a3\u8005\u4e2dpembrolizumab<\/span>\u4e0ePD-1 \u4f5c\u7528\u6d3b\u6027\u8fdb\u884c\u5bf9\u6bd4\uff0c\u7ed3\u679c\u663e\u793a\u836f<\/span>\u7269\u57282 \u79cd\u7fa4\u4f53\u7684\u4f5c\u7528\u6c34\u5e73\u76f8\u5f53\u3002<\/span><\/p>\n

\u65e9\u671fPK\/PD \u6a21\u578b\u4e2d\u60a3\u8005\u8840\u6db2\u6837\u672c\u7684\u7ed9\u836f\u540e\u4f53<\/span>\u5916IL-2 \u523a\u6fc0\u7387\u964d\u4f4e\uff0c\u95f4\u63a5\u53cd\u6620\u4e86\u5df2\u5b58\u5728\u9ad8\u6c34\u5e73\u7684\u5faa<\/span>\u73afT \u7ec6\u80dePD-1 \uff32O( \u5373\u53cd\u6620\u4e86\u9776\u6807\u7684\u53c2\u4e0e\u5ea6) \u3002<\/span><\/p>\n

\u66b4<\/span>\u9732\u91cf-\u6548\u5e94\u5173\u7cfb\u7684\u6a21\u62df\u7814\u7a76\uff0c\u5206\u6790\u4e86365 \u4f8b\u9ed1\u8272\u7d20\u7624<\/span>\u764c\u80bf\u7f29\u5c0f\u7684\u60a3\u8005\u8840\u836f\u6d53\u5ea6\u548c\u7597\u6548\u7684\u5173\u7cfb\uff0c\u7ed3\u679c\u63d0\u793a<\/span>1 mg\u00b7kg\u22121<\/span><\/sup>\uff0cQ3W \u53ef\u80fd\u5c31\u5df2\u8db3\u591f\u8fbe\u5230\u4e34\u5e8a\u6709\u6548\u5242\u91cf\u3002<\/span><\/p>\n

\u6b64\u5916\uff0cpembrolizumab \u4e5f\u5df2\u5728\u65e5\u672c\u4e0a\u5e02\uff0c\u4f46\u68c0\u7d22<\/span>PMDA \u7f51\u7ad9\uff0c\u672a\u89c1\u63d0\u4f9b\u8be5\u54c1\u7684\u516c\u5f00\u5ba1\u8bc4\u62a5\u544a\uff0c\u672c\u6587\u4e0d<\/span>\u4f5c\u63a2\u8ba8\u3002<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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3.3 atezolizumab<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u7533\u8bf7\u4eba\u5411FDA \u63d0\u4ea4\u4e862 \u9879\u652f\u6301\u6027\u2160\u671f\u4e34\u5e8a\u7814\u7a76PCD4989g( \u53c8\u79f0GO27831) \u548cJO28944\uff0c\u4ee5\u53ca\u4e00\u9879<\/span>\u5173\u952e\u6027\u2161\u671f\u4e34\u5e8a\u7814IMvigor210( \u53c8\u79f0GO29293) \u4f5c<\/span>\u4e3a\u6ce8\u518c\u7533\u8bf7\u7684\u652f\u6301\u4f9d\u636e\uff3b21\uff3d\u3002<\/span><\/p>\n

\u5728\u2160\u671f\u4e34\u5e8a\u7814\u7a76\u4e2d\u5242\u91cf\u9012\u589e\u8bd5\u9a8c\uff0c\u521d\u59cb\u8bbe\u8ba1\u4e860. 01 \uff5e 20 mg\u00b7kg\u22121<\/span><\/sup> \u6309\u4f53\u91cd\u7ed9\u836f\u7684\u5242\u91cf\uff0c\u4f46\u672a\u8fbe\u5230\u6700<\/span>\u5927\u8010\u53d7\u5242\u91cf\u3002\u7136\u540e\u5242\u91cf\u6269\u5c55\u65f6\u8bbe\u8ba1\u4e8615 mg\u00b7kg\u22121<\/span><\/sup>\u6309<\/span>\u4f53\u91cd\u7ed9\u836f\u7684\u5242\u91cf\u548c1 200 mg \u56fa\u5b9a\u5242\u91cf\uff0c2 \u79cd\u65b9\u5f0f\u5728<\/span>\u66b4\u9732\u91cf\u65b9\u9762\u6ca1\u6709\u4e34\u5e8a\u610f\u4e49\u5dee\u522b\u3002<\/span><\/p>\n

\u60a3\u8005\u63a5\u53d7\u5242\u91cf\u226510<\/span>mg\u00b7kg\u22121<\/span><\/sup> ( \u5305\u542b\u4e86\u56fa\u5b9a\u5242\u91cf1 200 mg) \u65f6\uff0catezolizumab<\/span>\u7a33\u6001\u8840\u6e05\u6d53\u5ea6\uff1e 6 \u03bcg\u00b7mL\u22121<\/span><\/sup>( \u6839\u636e\u975e\u4e34\u5e8a\u7ec4\u7ec7\u5206\u5e03<\/span><\/p>\n

\u53ca\u80bf\u7624\uff32O \u5206\u6790\u7684\u6570\u636e\uff0c\u8840\u836f\u6d53\u5ea66 \u03bcg\u00b7mL \uff0d 1\u8bbe\u4e3a\u9776\u8840\u6e05\u6d53\u5ea6) \u3002<\/span><\/p>\n

\u540c\u65f6\u5728\u2161\u671f\u4e34\u5e8a\u7814\u7a76\u4e2d\u9a8c\u8bc1\u4e86\u5c40\u665a\u671f<\/span>\u6216\u8f6c\u79fb\u6027\u5c3f\u8def\u4e0a\u76ae\u764c\u60a3\u8005\u7ed9\u4e881 200 mg \u56fa\u5b9a\u5242\u91cf\u3001<\/span>Q3W \u7684\u6709\u6548\u6027\u548c\u5b89\u5168\u6027\uff0c\u6240\u4ee5FDA \u5ba1\u8bc4\u610f\u89c1\u7684\u7ed3<\/span>\u8bba\u8ba4\u4e3a\u8be5\u4e34\u5e8a\u8bd5\u9a8c\u5df2\u5145\u5206\uff0c\u4e0d\u9700\u5242\u91cf\u8c03\u6574\u3002<\/span><\/p>\n

atezolizumab \u57281 \uff5e 20 mg\u00b7kg\u22121<\/span><\/sup> ( \u5305\u542b\u4e86\u56fa\u5b9a\u5242<\/span>\u91cf1 200 mg) \u5242\u91cf\u8303\u56f4\u5185PK \u5448\u7ebf\u6027\u7279\u5f81\uff0c\uff1c 1 mg\u00b7<\/span>kg\u22121<\/span><\/sup>\u5242\u91cf\u65f6\u836f\u7269\u66b4\u9732\u91cf\u4f4e\u4e8e\u5242\u91cf\u589e\u52a0\u7684\u6bd4\u4f8b\u3002<\/span><\/p>\n

\u57fa\u4e8e<\/span>2 \u9879\u2160\u671f\u4e34\u5e8a\u7814\u7a76\u5171\u7eb3\u5165472 \u4f8b\u60a3\u8005\u7684\u7fa4\u4f53PK \u5206<\/span>\u6790\u663e\u793a\uff0ct1 \/2<\/span>\u7ea6\u4e3a27 d\uff0cVss<\/span>\u4e3a6.9 L\uff0cCL \u4e3a0\uff0e 20 L\u00b7d\u22121<\/span><\/sup>\uff0c<\/span>\u7ed9\u836f\u540e\u836f\u7269\u6d53\u5ea6\u8fbe\u5230\u7a33\u6001\u7684\u65f6\u95f4\u4e3a6 \uff5e 9 \u5468( 2 \uff5e 3<\/span>\u5468\u671f) \uff0cAUC \u7684\u7cfb\u7edf\u7d2f\u79ef\u7387\u7ea6\u4e3a1. 9 \u500d\u3002<\/span><\/p>\n

\u6027\u522b\u3001\u4f53<\/span>\u91cd\u3001\u80bf\u7624\u5927\u5c0f\u3001\u8840\u6e05\u767d\u86cb\u767d\u6c34\u5e73\u3001ADA \u6c34\u5e73\u3001\u8f7b\u4e2d\u5ea6<\/span>\u80be\u635f\u4f24\u548c\u8f7b\u5ea6\u809d\u635f\u4f24\u7b49\u56e0\u7d20\uff0c\u5747\u4e0d\u9700\u8981\u8fdb\u884c\u5242\u91cf<\/span>\u8c03\u6574\u3002<\/span><\/p>\n

\u5728\u7fa4\u4f53PK \u5206\u6790\u4e2d\u79cd\u65cf\u56e0\u7d20\u4e0d\u662f\u6709\u610f\u4e49\u7684<\/span>\u534f\u53d8\u91cf\u3002<\/span><\/p>\n

1 200 mg\uff0cQ3W \u7ed9\u836f\u540e\u91cf\u6548\u5173\u7cfb\u5206\u6790\u7ed3\u679c\u663e\u793a\uff0catezolizumab \u7684\u7a33\u6001\u66b4\u9732\u91cf( AUCss<\/span>) \u65e0\u6cd5\u6709\u6548\u9884\u6d4b<\/span>\u60a3\u8005\u5ba2\u89c2\u7f13\u89e3\u7387( overall objective response rates\uff0c<\/span>O\uff32\uff32) \u6216\u4e0d\u826f\u4e8b\u4ef6( adverse events\uff0cAE) \u7684\u53d1\u751f\u7387\u3002<\/span><\/p>\n

PCD4989g \u7814\u7a76\u7684417 \u4f8b\u60a3\u8005\u7ed9\u836f\u5242\u91cf\u6700\u9ad8\u523020mg\u00b7kg\u22121<\/span><\/sup>\u6216\u56fa\u5b9a\u5242\u91cf1 200 mg\uff0c\u4f46\u7ed3\u679c\u5e76\u672a\u63d0\u793aatezolizumab<\/span>\u4f1a\u5ef6\u957f\u5fc3\u5ba4\u590d\u6781\u5316\u3002<\/span><\/p>\n

\u514d\u75ab\u539f\u6027:\u2161\u671fIMvigor 210 \u7814\u7a76\u3001\u2160\u671fPCD4989g\u548cJO28944 \u7814\u7a76\u4e2d\uff0c\u53ef\u68c0\u6d4b\u5230ADA \u9633\u6027\u7684\u60a3\u8005\u6bd4\u4f8b<\/span>\u5206\u522b\u4e3a41. 9% ( 161 \/384 ) \uff0c31. 7% ( 139 \/439 ) \u548c<\/span>16. 7%( 1 \/6) \uff0c\u8be5\u7814\u7a76\u4e2dADA \u7684\u5b58\u5728\u672a\u5bf9PK\u3001\u5b89\u5168<\/span>\u6027\u6216\u6709\u6548\u6027\u4ea7\u751f\u6709\u4e34\u5e8a\u610f\u4e49\u7684\u5f71\u54cd\u3002<\/span><\/p>\n

\u5bf9\u4e8e\u8be5\u4ea7\u54c1\u4f34\u968f\u5f00\u53d1\u7684biomarker\uff0cFDA \u8ba4\u4e3a\u867d<\/span>\u7136\u4e9a\u7ec4\u5206\u6790\u7ed3\u679c\u63d0\u793a\u80bf\u7624\u6d78\u6da6\u6027\u514d\u75ab\u7ec6\u80de\u7684PD-L1<\/span>\u8868\u8fbe\u91cf\u8bc4\u5206\u4e0e\u60a3\u8005\u7684O\uff32\uff32 \u5448\u6b63\u76f8\u5173\uff0c\u8be5\u6307\u6807\u4e5f\u53ef\u80fd<\/span>\u4f5c\u4e3a\u4e00\u79cd\u6709\u6548\u7684\u8f85\u52a9\u8bca\u65ad\uff0c\u4f46\u8fd9\u4e9b\u6570\u636e\u7684\u4e0a\u5e02\u524d\u6279<\/span>\u51c6\u8fd8\u5e94\u63d0\u4ea4\u5668\u68b0\u4e0e\u653e\u5c04\u5065\u5eb7\u4e2d\u5fc3( Center for Devices <\/span>and Radiological Health\uff0cCD\uff32H) \u8bc4\u4f30\u3002<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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3.4 avelumab<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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avelumab \u7528\u4e8eFDA \u7533\u8bf7\u65f6\u63d0\u4ea4\u4e863 \u9879\u4e34\u5e8a\u7814\u7a76\uff3b22\uff3d\uff0c\u5305\u62ec\u2160\u671f\u7814\u7a76Study EM\uff32100070-001\uff0c002\uff0c\u2161<\/span>\u671f\u6ce8\u518c\u6027\u4e34\u5e8a\u7814\u7a76Study EM\uff32100070-003( \u53ea\u6709Part<\/span>A \u6570\u636e\uff0c\u622a\u81f32016 \u5e743 \u67083 \u65e5Part B \u5c1a\u672a\u5165\u7ec4\u60a3\u8005) \u3002<\/span><\/p>\n

\u5728\u2160\u671f\u5242\u91cf\u9012\u589e\u8bd5\u9a8cStudy 001 \u4e2d\uff0c\u8003\u5bdf\u4e861. 0 \uff5e 20 mg\u00b7kg\u22121<\/span><\/sup>\u5242\u91cf\u8303\u56f4\u5185\u836f\u7269\u7684\u5b89\u5168\u6027\u548c\u8010\u53d7<\/span>\u6027\uff0c\u8bd5\u9a8c\u672a\u89c2\u5bdf\u5230\u6700\u5927\u8010\u53d7\u5242\u91cf( maximum tolerated <\/span>dose\uff0cMTD) \u3002<\/span><\/p>\n

\u6839\u636eStudy-001 \u4f53\u5916\u6570\u636e\u8bc4\u4f30\u5728\u5faa\u73af<\/span>CD3 + T \u7ec6\u80de\u4e0a\u7684PD-L1 \u9776\u70b9\u5360\u4f4d( target occupancy\uff0c<\/span>TO) \u60c5\u51b5\uff0c\u7ed3\u679c\u663e\u793a1 mg\u00b7kg \u22121<\/span><\/sup>\u7ec4\u30013 mg\u00b7kg\u22121<\/span><\/sup>\u7ec4\u3001<\/span>10 mg\u00b7kg\u22121<\/span><\/sup>\u7ec4\u548c20 mg\u00b7kg\u22121<\/span><\/sup>\u7ec4\u5728\u7b2c2 \u6b21\u7ed9\u836f\u4e4b\u524d<\/span>( 15 d) \uff0c\u5e73\u5747TO \u5206\u522b\u8fbe\u5230\u4e86( 75. 7 \u00b1 22. 1 ) %\uff0c<\/span>( 90 \u00b1 8. 1) %\uff0c( 93. 2 \u00b1 1. 3) % \u548c( 85 \u00b1 8. 7) %\u3002<\/span><\/p>\n

\u57fa<\/span>\u4e8e\u4e0a\u8ff0\u7814\u7a76\u7ed3\u679c\uff0c\u6700\u7ec8\u63a8\u8350\u5242\u91cf\u4e3a10 mg\u00b7kg\u22121<\/span><\/sup>\uff0c<\/span>Q2W\u3002<\/span><\/p>\n

\u57fa\u4e8eStudy 001 \uff5e 003 \u7814\u7a76\u6df7\u5408\u6570\u636e\u7684\u7fa4\u4f53PK\u5206\u6790\u7ed3\u679c\u663e\u793a\uff0cavelumab \u5728\u7279\u5b9a\u4eba\u7fa4( \u9ed8\u514b\u5c14\u7ec6\u80de<\/span>\u764c\u60a3\u8005\u53ca\u5176\u4ed6\u5c40\u665a\u671f\u6216\u8f6c\u79fb\u6027\u5b9e\u4f53\u7624\u60a3\u8005) \u4e2d\u7684CL<\/span>\u7ea6\u4e3a0\uff0e 024 6 L\u00b7h\u22121<\/span><\/sup>\uff0cVss<\/span>\u7ea6\u4e3a4.72 L\uff0ct1 \/2<\/span>\u7ea6\u4e3a6.1 d\uff0c<\/span>\u57284 \uff5e 6 \u5468\u8fbe\u5230\u7a33\u6001\u6d53\u5ea6\u4e14\u7d2f\u79ef\u6307\u6570\u4e3a1.25 \u500d\u3002<\/span><\/p>\n

\u5728<\/span>10 \uff5e 20 mg\u00b7kg\u22121<\/span><\/sup>\uff0cQ2W \u5242\u91cf\u8303\u56f4\u5185\uff0cavelumab \u66b4\u9732<\/span>\u91cf\u589e\u52a0\u4e0e\u5242\u91cf\u5448\u7ebf\u6027\uff3b23\uff3d\u3002\u4f53\u91cd\u5bf9CL\u3001V1\u3001\u5916\u5468\u5ba4\u5206<\/span>\u5e03\u5bb9\u79ef( V2<\/span>) \u7b493 \u4e2a\u53c2\u6570\u6709\u5f71\u54cd\uff0c\u968f\u7740\u4f53\u91cd\u589e\u52a0\uff0cCL<\/span>\u7b49\u53c2\u6570\u589e\u5927\u3002\u867d\u7136\u89c2\u5bdf\u5230\u7537\u6027\u60a3\u8005\u7684CL \u548cV1<\/span>\u6bd4\u5973\u6027\u60a3\u8005\u5206\u522b\u5347\u9ad819.9%\u548c20. 3%\uff0c\u4f46\u6b64\u53d8\u5316\u5728\u6a21\u62df<\/span>\u4e0d\u540c\u6027\u522b\u7684AUCss<\/span>\u65f6\u672a\u663e\u793a\u6709\u4e34\u5e8a\u610f\u4e49\u7684\u5dee\u522b\u3002<\/span><\/p>\n

\u809d<\/span>\u80be\u529f\u80fd\u7684\u635f\u4f24\u5bf9CL \u6ca1\u6709\u5f71\u54cd\uff0c\u6240\u4ee5\u65e0\u9700\u5728\u6b64\u7c7b\u7fa4<\/span>\u4f53\u4e2d\u8fdb\u884c\u5242\u91cf\u8c03\u6574\u3002<\/span><\/p>\n

\u8be5\u7814\u7a76\u4e2d\u6d89\u53ca\u7684\u4f34\u968f\u6cbb\u7597\u836f\u7269<\/span>\u672a\u5bf9avelumab \u7684\u6e05\u9664\u4ea7\u751f\u5f71\u54cd\u3002\u5728Study001 \u4e2d\u8fde<\/span>\u7eed85 d \u76d1\u6d4b\u4e86\u7ed9\u836f1 \uff5e 20 mg\u00b7kg\u22121<\/span><\/sup> \u540e\uff0c IL-1\u03b2\uff0c IL-2\uff0c<\/span>IL-4\uff0c IL-6\uff0c IL-10\uff0c IFN-\u03b3 \u548cTNF-\u03b1 \u7b49\u4e3b\u8981\u5faa\u73af\u7ec6\u80de\u56e0<\/span>\u5b50\u7684\u8840\u6e05\u6d53\u5ea6\u6c34\u5e73\uff0c\u5728\u4e0d\u540c\u5242\u91cf\u7ed9\u836f\u540e\u7684IFN-\u03b3 \u548c<\/span>TNF-\u03b1 \u5728\u4e0d\u540c\u65f6\u95f4\u66fe\u51fa\u73b0\u4e00\u8fc7\u6027\u5347\u9ad8\uff0c\u4f46\u662f\u53d1\u751f\u6ca1<\/span>\u6709\u56fa\u5b9a\u89c4\u5f8b\u3002<\/span><\/p>\n

\u91cf\u6548\u5173\u7cfb\u9884\u6d4b\u4e86\u7a33\u6001\u8840\u836f\u8c37\u503c\u6d53\u5ea6( Ctrough\uff0css)<\/span>\u4e0e\u6700\u4f73\u603b\u4f53\u5e94\u7b54( best overall response\uff0cBO\uff32) \u7684\u5173<\/span>\u7cfb\uff0c\u5728\u8f6c\u79fb\u6027\u9ed8\u514b\u5c14\u7ec6\u80de\u764c\u60a3\u8005\u4e2d\u4e24\u8005\u88ab\u8ba4\u4e3a\u5448\u6b63<\/span>\u76f8\u5173\u3002<\/span><\/p>\n

avelumab \u7684\u66b4\u9732\u91cf\u5bf9\u514d\u75ab\u76f8\u5173\u7684AE \u53d1\u751f\u7387<\/span>\u589e\u52a0\u53ef\u80fd\u6709\u8f83\u5f31\u5f71\u54cd\uff0c\u5bf9\u6cbb\u7597\u76f8\u5173\u7684AE \u6216\u8f93\u6ce8\u76f8<\/span>\u5173\u7684AE( \u53d1\u751f\u7387\u7ea621\uff0e 6%) \u5219\u9884\u8ba1\u6ca1\u6709\u5f71\u54cd\u3002<\/span><\/p>\n

avelumab<\/span>\u5bf9QTc<\/span>\u6216\u0394QTc<\/span>\u5f71\u54cd\u5f88\u5c0f\uff0c\u63d0\u793a\u4e86\u8be5\u836f\u5bf9\u5fc3\u810f<\/span>\u590d\u6781\u5316\u7684\u5f71\u54cd\u6ca1\u6709\u4e34\u5e8a\u610f\u4e49\u3002<\/span><\/p>\n

\u514d\u75ab\u539f\u6027\u5206\u6790\u663e\u793a\uff0c\u6cbb\u7597\u76f8\u5173\u7684ADA \u53d1\u751f\u7387\u4e3a3.5%( 49 \/1 383) \uff0c\u5448\u9633\u6027\u6297\u4f53\u7684\u6ef4\u5ea6\u666e\u904d\u8f83\u4f4e\uff0c\u514d<\/span>\u75ab\u539f\u6027\u5e94\u7b54\u7684\u6301\u7eed\u65f6\u95f4\u548c\u6700\u5927\u89c2\u6d4b\u6ef4\u5ea6\u4e4b\u95f4\u6ca1\u6709\u660e<\/span>\u786e\u5173\u7cfb\u3002<\/span><\/p>\n

ADA \u9633\u6027\u60a3\u8005\u6bd4\u6297\u4f53\u5448\u9634\u6027\u7684\u60a3\u8005\u6709\u66f4<\/span>\u9ad8\u7684\u6ce8\u5c04\u53cd\u5e94\u53d1\u751f\u7387( 33.9% vs 24.1%) \uff0c\u51fa\u73b0<\/span>ADA \u9633\u6027\u76844 \u4f8b\u60a3\u8005\u4e2d\u67093 \u4f8b\u56e0\u6ce8\u5c04\u53cd\u5e94\u800c\u4e2d\u6b62<\/span>\u6cbb\u7597\uff0c\u8bc4\u4f30\u8ba4\u4e3a\u6297\u4f53\u9633\u6027\u53ef\u80fd\u4e0e\u6ce8\u5c04\u53cd\u5e94\u6709\u4e00\u5b9a\u5173<\/span>\u8054\uff0c\u4f46\u5e76\u975e\u56e0\u679c\u5173\u7cfb\u3002<\/span><\/p>\n

ADA \u7684\u5b58\u5728\u6ca1\u6709\u963b\u65adavelumab<\/span>\u6cbb\u7597\u7684\u9996\u6b21\u5e94\u7b54\uff0cADA \u8840\u6e05\u8f6c\u6362\u540e\u4e5f\u6ca1\u6709\u963b<\/span>\u65ad\u6301\u7eed\u6027\u5e94\u7b54\u3002<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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3.5 durvalumab<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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durvalumab \u7684\u6709\u6548\u6027\u548c\u5b89\u5168\u6027\u652f\u6301\u6027\u6570\u636e\u662f\u57fa\u4e8e\u9996\u6b21\u4eba\u4f53\u8bd5\u9a8cStudy1108 \u548c\u975e\u5c0f\u7ec6\u80de\u80ba\u764c\u60a3\u8005\u4f53<\/span>\u5185\u7684Study ATLANTIC \u7814\u7a76\uff3b24\uff3d\uff0c\u5176\u4e2dStudy1108 \u662f\u9488<\/span>\u5bf9\u665a\u671f\u6216\u8f6c\u79fb\u6027\u5c3f\u8def\u4e0a\u76ae\u764c\u60a3\u8005\u7684\u7814\u7a76\u3002<\/span>\u63a5\u53d710 mg\u00b7kg \u22121<\/span><\/sup>\uff0cQ2W \u7684\u5242\u91cf\u9009\u62e9\u4f9d\u636e\u662f: \u6309<\/span>\u7167\u6b64\u5242\u91cf\u7ed9\u836f\u5728\u76ee\u6807\u60a3\u8005\u4eba\u7fa4\u4e2d\u7684\u5b89\u5168\u6027\u8303\u56f4\u3001\u4e34<\/span>\u5e8a\u6709\u6548\u6027\u7ed3\u679c\u7684\u652f\u6301\uff0c\u4ee5\u53ca\u572895% \u4ee5\u4e0a\u7684\u60a3\u8005\u4e2d\u8fbe<\/span>\u5230\u671f\u671b\u7684\u8c37\u6d53\u5ea650 \u03bcg\u00b7mL\u22121<\/span><\/sup>\uff0c\u975e\u4e34\u5e8a\u53ca\u4e34\u5e8a\u6570\u636e\u663e<\/span>\u793a\u6b64\u8840\u836f\u6d53\u5ea6\uff1e 99%\u7684\u9776\u70b9\u9971\u548c\u3002<\/span><\/p>\n

\u5728\u22653 mg\u00b7kg\u22121<\/span><\/sup>\u7684\u5242\u91cf\u8303\u56f4\u5185\uff0cdurvalumab \u5448\u7ebf\u6027PK \u7279\u5f81; \uff1c3 mg\u00b7kg \u22121<\/span><\/sup>\u5242\u91cf\u65f6\uff0c\u5448\u975e\u7ebf\u6027PK \u7279\u5f81\u3002<\/span><\/p>\n

\u5bf91 418 \u4f8b\u60a3\u8005\u63a5\u53d7\u4e860 .1 \uff5e 10 mg\u00b7kg\u22121<\/span><\/sup>\uff0cQ2W\uff0c<\/span>15 mg\u00b7kg\u22121<\/span><\/sup>\uff0cQ3W \u621620 mg\u00b7kg\u22121<\/span><\/sup>\uff0cQ4W \u7684\u5242\u91cf\u6240\u83b7<\/span>\u6570\u636e\u8fdb\u884c\u7fa4\u4f53PK \u5206\u6790\u663e\u793a\uff0cCL \u968f\u65f6\u95f4\u51cf\u5c0f\uff0c\u4e0e\u57fa<\/span>\u7ebf\u503c\u76f8\u6bd4CL \u5e73\u5747\u6700\u5927\u4e0b\u964d\u5e45\u5ea6\u4e3a22.9%\uff0c\u63d0\u793a<\/span>durvalumab \u5448\u65f6\u95f4\u4f9d\u8d56\u6027\u6d88\u9664\u3002\u7a33\u6001CL \u4e3a8. 2<\/span>mL\u00b7h\u22121<\/span><\/sup>\uff0cVss\u4e3a5.6 L\uff0ct1 \/2<\/span>\u4e3a17 d\uff0c10 mg\u00b7kg\u22121<\/span><\/sup>\uff0cQ2W \u7ed9<\/span>\u836f\u540e\u7ea616 \u5468\u8fbe\u5230\u7a33\u6001\u6d53\u5ea6\uff0cAUC \u7684\u7cfb\u7edf\u7d2f\u79ef\u6307\u6570\u7ea6\u4e3a4. 3 \u500d\u3002<\/span><\/p>\n

\u5728\u62df\u7528\u5242\u91cf\u4e0b\uff0c\u4f53\u91cd\u3001\u6027\u522b\u3001\u5e74\u9f84\u3001\u79cd<\/span>\u65cf\u3001\u8840\u6e05\u767d\u86cb\u767d\u3001\u7ed9\u836f\u540eADA\u3001\u4f53\u529b\u72b6\u6001\u3001\u80bf\u7624\u7c7b\u578b\u3001<\/span>\u8f7b\u4e2d\u5ea6\u80be\u635f\u4f24\u3001\u8f7b\u5ea6\u809d\u635f\u4f24\u7b49\u56e0\u7d20\uff0c\u5bf9durvalumab<\/span>\u7684PK \u53c2\u6570\u5f71\u54cd\u5747\u6ca1\u6709\u4e34\u5e8a\u610f\u4e49\uff0c\u6240\u4ee5\u4e0d\u9700\u8c03\u6574\u4e2a<\/span>\u4f53\u5242\u91cf\u3002<\/span><\/p>\n

\u5728\u6240\u6709durvalumab \u7ed9\u836f\u60a3\u8005\u4e2d\uff0c\u5747\u89c2\u5bdf\u5230\u6e38\u79bb\u8840\u6e05PD-L1 \u6c34\u5e73\u5448\u5242\u91cf\u4f9d\u8d56\u6027\u6291\u5236\u3002\u5728\uff1e 0. 3 mg\u00b7<\/span>kg\u22121<\/span><\/sup>\uff0cQ2W \u5242\u91cf\u7ed9\u836f\u65f6\u5927\u591a\u6570\u60a3\u8005\u7684PD-L1 \u6c34\u5e73\u90fd<\/span>\u4f4e\u4e8e\u5b9a\u91cf\u9650( 67.1 pg\u00b7mL\u22121<\/span><\/sup> ) \u3002<\/span><\/p>\n

\u5728Study 1108 \u7814\u7a76\u4e2d<\/span>\u8bc1\u5b9e\uff0c\u7ea693\uff0e 3% ( 781 \/837) \u7684\u60a3\u8005\u572810 mg\u00b7kg\u22121<\/span><\/sup>\uff0c<\/span>Q2W \u7ed9\u836f\u671f\u95f4PD-L1 \u88ab\u5b8c\u5168\u6291\u5236\u3002\u53e6\u59162 \u9879\u7ecf\u9a8c<\/span><\/p>\n

\u8bc1\u7684\u6d41\u5f0f\u7ec6\u80de\u5206\u6790\u6cd5\u5bf959 \u4f8b\u5c3f\u8def\u4e0a\u76ae\u764c\u60a3\u8005\u7684\u5faa\u73af\u6dcb\u5df4\u7ec6\u80de\u548c\u589e\u6b96T \u7ec6\u80de\u4e9a\u7fa4\u8fdb\u884c\u5b9a\u91cf\uff0c\u7ed9\u836f\u540e<\/span>d 10 \u548cd 15 \u589e\u6b96CD8 + T \u7ec6\u80de\u6570\u91cf\u5347\u9ad8\uff0cCD4 + T \u7ec6<\/span>\u80de\u5728d 10 \u65f6\u8d8b\u52bf\u4e00\u81f4\u3002<\/span><\/p>\n

\u91cf\u6548\u5173\u7cfb\u5206\u6790\u663e\u793a10 mg\u00b7kg\u22121<\/span><\/sup>\uff0cQ2W \u5242\u91cf\u4e0b\uff0c\u5b89\u5168\u6027\u4e8b\u4ef6( \u59823 \u7ea7\u4ee5\u4e0a\u7684AE\u3001\u5bfc\u81f4\u505c\u836f\u7684AE \u7b49)<\/span>\u6ca1\u6709\u663e\u8457\u7684\u91cf\u6548\u5173\u7cfb\uff0c\u603b\u4f53\u5b89\u5168\u6027\u4e8b\u4ef6\u53d1\u751f\u7387\u8f83\u4f4e;<\/span>\u7531\u4e8e\u76f8\u5173\u7814\u7a76\u4ec5\u5305\u542b\u4e86\u4e00\u4e2a\u5242\u91cf\u6c34\u5e73\uff0c\u7f3a\u4e4f\u5bf9\u6bd4\uff0c\u6240<\/span>\u4ee5\u6709\u6548\u6027( \u6bd4\u5982O\uff32\uff32) \u7684\u91cf\u6548\u5173\u7cfb\u5c1a\u4e0d\u786e\u5b9a\uff0c\u9700\u8981\u540e<\/span>\u7eed\u66f4\u591a\u6570\u636e\u89e3\u91ca\u3002Study ATLANTIC \u7814\u7a76\u7684QTc<\/span>\u4e9a<\/span>\u7ec4\u5206\u6790\u8ba4\u4e3a\u8be5\u836f\u4e0d\u4f1a\u5ef6\u957f\u5fc3\u810f\u590d\u6781\u5316\u4f5c\u7528\u3002<\/span><\/p>\n

\u514d\u75ab\u539f\u6027\u5206\u6790\u663e\u793a\uff0cStudy 1108 \u548cStudy ATLANTIC<\/span>\u4e2d\u5206\u522b\u67093.3% ( 37\/1124) \u548c4. 3% ( 16 \/<\/span>373) \u7684\u8bc4\u4f30\u60a3\u8005\u5448ADA \u9633\u6027( \u4f46\u8be5\u5206\u6790\u7ed3\u679c\u53ef\u9760<\/span>\u6027\u6b20\u4f73) \u3002<\/span><\/p>\n

\u7fa4\u4f53PK \u5206\u6790\u663e\u793aADA \u5bf9PK \u53c2\u6570\u6ca1\u6709<\/span>\u5f71\u54cd\uff0c\u4f46\u662f\u7531\u4e8e\u6cbb\u7597\u4ea7\u751fADA \u548c\u76f8\u5bf9ORR\u4f4e\u3001\u4e14<\/span>ADA \u9633\u6027\u7684\u60a3\u8005\u6837\u672c\u91cf\u592a\u5c11\uff0c\u6240\u4ee5\u5bf9\u6709\u6548\u6027\u548c\u5b89\u5168<\/span>\u6027\u7684\u5f71\u54cd\u65e0\u6cd5\u8bc4\u4f30\u3002<\/span><\/p>\n

\u7531\u4e8e\u7533\u8bf7\u4eba\u53ea\u5bf9ADA \u5206\u6790\u8fdb<\/span>\u884c\u4e86\u65b9\u6cd5\u5b66\u9a8c\u8bc1\uff0cADA \u786e\u8bc1\u548c\u4e2d\u548c\u6297\u4f53\u5206\u6790\u7684\u65b9\u6cd5<\/span>\u5b66\u5efa\u7acb\u7684\u4e0d\u591f\u5145\u5206\uff0cFDA \u8981\u6c42\u7533\u8bf7\u4eba\u627f\u8bfa\u4e0a\u5e02\u540e\u8fd8<\/span>\u4f1a\u5bf9\u8fd9\u4e9b\u5206\u6790\u65b9\u6cd5\u4f5c\u8fdb\u4e00\u6b65\u9a8c\u8bc1\u3002<\/p>\n

\u901a\u8fc7\u5bf9PD-L1 \u8868\u8fbe\u91cf\u7684\u4e9a\u7ec4\u5206\u6790\u663e\u793a\uff0cPD-L1<\/span>\u9ad8\u8868\u8fbe\u7684\u4e9a\u7ec4\u60a3\u8005\u5176O\uff32\uff32 \u6c34\u5e73\u4e5f\u8f83\u9ad8( 19. 0% vs<\/span>\u8868\u8fbe\u91cf\u4f4e\u7684\u4e9a\u7ec43. 6%) \u3002<\/span><\/p>\n

FDA \u540c\u65f6\u6279\u51c6\u4e86VENTANA<\/span>PD-L1 ( SP263) Assay \u4f5c\u4e3aBiomarker \u5bf9\u5c3f\u8def<\/span>\u4e0a\u76ae\u764c\u7ec4\u7ec7\u4e2dPD-L1 \u86cb\u767d\u6c34\u5e73\u8f85\u52a9\u8bca\u65ad\uff3b25\uff3d\u3002<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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4<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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PD-1 \/PD-L1 \u6297\u4f53\u836f\u7269\u7684\u4e34\u5e8a\u836f\u7406\u5b66\u7814\u7a76\u5173\u6ce8\u70b9<\/strong><\/p>\n<\/section>\n<\/section>\n

<\/section>\n<\/section>\n<\/section>\n<\/section>\n
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\u4e0d\u540c\u4e8e\u4f20\u7edf\u7684\u5c0f\u5206\u5b50\u5316\u5b66\u836f\uff0cPD-1 \/PD-L1 \u6297\u4f53\u7b49\u6cbb\u7597\u6027\u86cb\u767d\u836f\u7269\u5927\u591a\u901a\u8fc7\u9759\u8109\u8f93\u6ce8\u7ed9\u836f\uff0c\u6240\u4ee5\u4e00<\/span>\u822c\u5bf9\u836f\u7269\u5438\u6536\u3001\u751f\u7269\u5229\u7528\u5ea6\u6216\u98df\u7269\u5f71\u54cd\u7b49\u56e0\u7d20\u4e0d\u4f5c<\/span>\u5355\u72ec\u7684\u8bd5\u9a8c\u8003\u5bdf\uff0c\u540c\u65f6\u7531\u4e8e\u5355\u6297\u836f\u7269\u964d\u89e3\u4ee3\u8c22\u540e\u53d8<\/span>\u4e3a\u5c0f\u80bd\u548c\u6c28\u57fa\u9178\uff0c\u5728\u4f53\u5185\u4f1a\u8fdb\u5165\u4f53\u5faa\u73af\u88ab\u5176\u4ed6\u86cb\u767d<\/span>\u518d\u5229\u7528\uff0c\u6240\u4ee5\u4e34\u5e8a\u836f\u7406\u5b66\u7814\u7a76\u5e38\u89c4\u5173\u6ce8\u7684\u8d28\u91cf\u5e73\u8861\u3001<\/span>\u836f\u7269\u4ee3\u8c22\u548c\u6392\u6cc4\u7279\u5f81\u7b49\u95ee\u9898\u5bf9\u6cbb\u7597\u6027\u86cb\u767d\u836f\u7269\u5e76\u4e0d<\/span>\u9002\u7528\uff3b19\uff3d\u3002<\/span><\/p>\n

\u6cbb\u7597\u6027\u86cb\u767d\u836f\u7269\u7684\u76f8\u5bf9\u5206\u5b50\u8d28\u91cf\u8f83\u5927\uff0c\u76f4<\/span>\u63a5\u5bf9\u79bb\u5b50\u901a\u9053\u4f5c\u7528\u7684\u53ef\u80fd\u6027\u5f88\u4f4e\uff0c\u6240\u4ee5\u5927\u591a\u672a\u8003\u5bdf<\/span>\u836f\u7269\u76f8\u4e92\u4f5c\u7528\uff3b21\uff3d\u3002<\/span><\/p>\n

\u4e0a\u8ff05 \u79cd\u5355\u6297\u4ea7\u54c1\u5728FDA\uff0cEMA \u548cPMDA \u6ce8\u518c\u7533\u8bf7\u65f6\uff0c\u5bf9\u4e34\u5e8a\u836f\u7406\u5b66\u7814\u7a76\u4e3b\u8981\u8003\u5bdf\u5e76\u56de\u7b54\u4e86\u4ee5\u4e0b<\/span>\u51e0\u65b9\u9762\u7684\u95ee\u9898: \u4e34\u5e8a\u5242\u91cf\u3001\u7ed9\u836f\u65b9\u6cd5\u5982\u4f55\u9009\u62e9\uff0c\u836f\u7269<\/span>\u53ca\u5176\u4ee3\u8c22\u7269\u7684PK \u7279\u5f81\u53ca\u4e3b\u8981\u53c2\u6570\uff0c\u91cf\u6548\u5173\u7cfb\uff0c\u5e74<\/span>\u9f84\u3001\u6027\u522b\u3001\u4f53\u91cd\u3001\u79cd\u65cf\u7b49\u5185\u5728\u56e0\u7d20\u7684\u5f71\u54cd\u5dee\u5f02\uff0c\u514d\u75ab\u539f<\/span>\u6027\u53ca\u5bf9PK \u7684\u5f71\u54cd\u7b49\u3002<\/span><\/p>\n

\u5176\u4e2d\uff0c\u5bf9\u4e8ePK \u7279\u5f81\u7684\u9610\u8ff0\u53ca<\/span>\u5206\u6790\u5f71\u54cd\u56e0\u7d20\u65f6\uff0c\u8fd95 \u4e2a\u4ea7\u54c1\u7684\u7814\u7a76\u5747\u8fdb\u884c\u4e86\u6570\u636e<\/span>\u96c6\u6c47\u603b\u540e\u7684\u7fa4\u4f53PK \u5206\u6790\uff0c\u4ee5\u671f\u53d1\u73b0\u5f71\u54cd\u836f\u7269\u7279\u6027<\/span><\/p>\n

\u7684\u56e0\u7d20\u6216\u89e3\u91ca\u5728\u76ee\u6807\u4eba\u7fa4\u4e2d\u7684\u53d8\u5f02\uff3b26\uff3d\u3002<\/p>\n

\u4ece\u836f\u7269\u6027\u8d28\u7684\u89d2\u5ea6\u800c\u8a00\uff0c\u8fd9\u7c7b\u5355\u6297\u4ea7\u54c1\u5177\u6709\u4e00\u5b9a\u5171\u6027\u7684\u4e34\u5e8a\u836f\u7406\u5b66\u7279\u5f81( \u89c1\u88683) \uff0c\u5982\u76f8\u5bf9\u5206\u5b50\u8d28<\/span>\u91cf\u5927\u3001\u534a\u8870\u671f\u8f83\u957f\uff0c\u836f\u7269\u6e05\u9664\u7387\u5448\u65f6\u95f4\u4f9d\u8d56\u6027\u7b49\uff0c\u6240<\/span>\u4ee5\u5728\u836f\u7269\u7814\u53d1\u548c\u5ba1\u8bc4\u65f6\u90fd\u9700\u5173\u6ce8\u7814\u7a76\u6240\u5f97\u7ed3\u8bba\u4e0e\u5df2<\/span>\u6709\u4fe1\u606f\u6216\u8ba4\u77e5\u662f\u5426\u4e00\u81f4\uff0c\u5c24\u5176\u662f\u5982\u679c\u65e0\u6cd5\u5408\u7406\u89e3\u91ca<\/span>\u65f6\u4ecd\u9700\u8fdb\u4e00\u6b65\u7814\u7a76\u9a8c\u8bc1\u3002<\/p>\n

\"PD-1\/PD-L1<\/p>\n

\u5df2\u4e0a\u5e02\u76845 \u79cdPD-1 \/PD-L1 \u6297\u4f53\u7684\u68c0\u6d4b\u65b9\u6cd5\u4e3b\u8981\u91c7\u7528\u4e86\u9176\u8054\u514d\u75ab\u5438\u9644\u5206\u6790\u6cd5( enzyme-linked immunosorbent <\/span>assay\uff0cELISA) \u6216\u7535\u5316\u5b66\u53d1\u5149\u514d\u75ab\u5206\u6790<\/span>\u6cd5( electro chemiluminescence immunoassay\uff0cECLIA)<\/span>\u68c0\u6d4b\u4eba\u8840\u6e05\u4e2d\u7684\u5f85\u6d4b\u836f\u7269; \u800cADA \u7684\u68c0\u6d4b\u65b9\u6cd5\u6709\u7ade<\/span>\u4e89\u6027\u3001\u6865\u8fde\u6027ELISA \u6cd5\u6216ECLIA \u6cd5\u7b49\u3002<\/span><\/p>\n

\u65e0\u8bba\u91c7\u7528\u54ea<\/span>\u79cd\u5206\u6790\u65b9\u6cd5\uff0c\u5176\u65b9\u6cd5\u5b66\u5747\u9700\u8fdb\u884c\u5408\u7406\u53ef\u9760\u5730\u9a8c\u8bc1\u3002<\/span><\/p>\n

\u5f53\u540c\u4e00\u79cd\u836f\u7269\u7684\u7814\u7a76\u4e2d\u5982\u679c\u91c7\u7528\u82e5\u5e72\u79cd\u4e0d\u540c\u7684\u65b9\u6cd5\u8fdb\u884c\u68c0\u6d4b\u65f6\uff0c\u5e94\u5bf9\u8fd9\u4e9b\u65b9\u6cd5\u8fdb\u884c\u5bf9\u6bd4\u9a8c\u8bc1\uff0c\u5fc5\u8981\u65f6\u8fd8<\/span>\u5e94\u91c7\u7528\u4e0d\u540c\u65b9\u6cd5\u5bf9\u751f\u7269\u6837\u672c\u8fdb\u884c\u590d\u6d4b\uff0c\u4ee5\u4fdd\u8bc1\u6570\u636e<\/span>\u7684\u76f8\u5bf9\u51c6\u786e\u6027\u548c\u4e00\u81f4\u6027\u3002\u6bd4\u5982\uff0c\u652f\u6301nivolumab \u5728\u65e5<\/span>\u672c\u4e0a\u5e02\u76844 \u9879\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\uff0c\u91c7\u7528\u4e864 \u79cd\u4e0d\u540c\u7684<\/span>ECLIA \u6cd5\u6d4b\u5b9a\u4eba\u8840\u6e05\u4e2d\u7684ADA\uff0c\u7533\u8bf7\u4eba\u5bf9\u8fd94 \u79cd\u65b9<\/span>\u6cd5\u8fdb\u884c\u4e86\u6bd4\u8f83\u548c\u603b\u7ed3\uff0c\u8ba4\u4e3a\u524d3 \u79cd\u65b9\u6cd5\u5bf9\u7ed3\u679c\u8f83\u4e00<\/span>\u81f4\uff0c\u7b2c4 \u79cd\u65b9\u6cd5\u6d4b\u5b9a\u503c\u8f83\u4f4e\u3002\u6240\u4ee5\u63d0\u4f9b\u7684\u65e5\u672c\u5730\u533a<\/span>\u7684\u7814\u7a76\u6570\u636e\u9664\u4e86\u4f7f\u7528\u65b9\u6cd52 \u68c0\u6d4b\u4e4b\u5916\uff0c\u7528\u65b9\u6cd54 \u53c8<\/span>\u5168\u90e8\u590d\u6d4b\u4e00\u6b21\uff3b16\uff3d\u3002<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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5<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u80bf\u7624\u514d\u75ab\u68c0\u67e5\u70b9\u6291\u5236\u5242\u901a\u8fc7\u6291\u5236\u514d\u75ab\u68c0\u67e5\u70b9\u6d3b\u6027\uff0c\u91ca\u653e\u80bf\u7624\u5fae\u73af\u5883\u4e2d\u7684\u201c\u514d\u75ab\u5239\u8f66\u201d\uff0c\u91cd\u65b0\u6fc0\u6d3bT<\/span>\u7ec6\u80de\u5bf9\u80bf\u7624\u7684\u514d\u75ab\u5e94\u7b54\u3002\u514d\u75ab\u68c0\u67e5\u70b9\u6291\u5236\u5242\u826f\u597d\u7684<\/span>\u4e34\u5e8a\u7597\u6548\u5df2\u5728\u9ed1\u8272\u7d20\u7624\u3001\u975e\u5c0f\u7ec6\u80de\u80ba\u764c\u7b49\u591a\u79cd\u5b9e\u4f53<\/span>\u7624\u60a3\u8005\u4eba\u7fa4\u4e2d\u5f97\u5230\u5370\u8bc1\u3002<\/span><\/p>\n

\u76ee\u524d\u4e00\u4e9b\u80bf\u7624\u76f8\u5173\u9002\u5e94\u8bc1<\/span>\u7684\u4e34\u5e8a\u6cbb\u7597\u5c1a\u65e0\u6cbb\u6108\u65b9\u6cd5\u3002\u4e3a\u4e86\u8ba9\u60a3\u8005\u83b7\u5f97\u66f4\u591a\u6709<\/span>\u6548\u7684\u65b0\u836f\uff0c\u8fd1\u5e74\u6765\u57fa\u4e8ePD-1 \/PD-L1 \u514d\u75ab\u68c0\u67e5\u70b9\u6291<\/span>\u5236\u5242\u7684\u836f\u7269\u5728\u56fd\u5916\u76d1\u7ba1\u673a\u6784\u4e0a\u5e02\u65f6\uff0c\u57fa\u672c\u5747\u83b7\u5f97\u4e86\u52a0\u901f\u5ba1\u6279\u3001\u4f18\u5148\u5ba1\u8bc4\u6216\u7a81\u7834\u6027\u7597\u6cd5\u7684\u6307\u5b9a\u8d44\u683c\u3002<\/span><\/p>\n

\u8fd1\u5e74\u6765\uff0cPD-1 \/PD-L1 \u6297\u4f53\u8054\u5408\u5176\u4ed6\u514d\u75ab\u6291\u5236\u901a\u8def\u6297\u4f53\uff3b28-29\uff3d\u3001\u9776\u5411\u6cbb\u7597\uff3b30\uff3d\u3001CA\uff32-T \u7ec6\u80de\u514d\u75ab\uff3b31\uff3d\u53ca<\/span>\u5316\u5b66\u6cbb\u7597\u7b49\uff3b32\uff3d\u4e00\u4e9b\u6cbb\u7597\u7b56\u7565\u5df2\u8fdb\u5165\u4e34\u5e8a\u8bd5\u9a8c\uff0c\u5e76\u663e<\/span>\u793a\u4e86\u4e00\u5b9a\u7684\u5e94\u7528\u524d\u666f\uff3b33 \uff0d 34\uff3d\u3002<\/span><\/p>\n

\u4e0d\u8fc7\uff0c\u540c\u65f6\u4e5f\u9700\u8981\u5bc6\u5207<\/span>\u5173\u6ce8\u8054\u5408\u6cbb\u7597\u540e\u4e0d\u826f\u53cd\u5e94\u7684\u53d1\u751f\u60c5\u51b5\uff0c\u6709\u62a5\u9053\u663e\u793a<\/span>\u514d\u75ab\u6cbb\u7597\u7684\u8054\u5408\u5e94\u7528\u66f4\u6709\u53ef\u80fd\u5bfc\u81f4\u9ad8\u7ea7\u522b\u3001\u514d\u75ab\u76f8<\/span>\u5173AE \u7684\u53d1\u751f\uff0c\u6bd4\u5982\u66b4\u53d1\u6027\u81f4\u6b7b\u6027\u5fc3\u808c\u708e\uff3b35\uff3d\u3002<\/span><\/p>\n

PD-<\/span>1 \/PD-L1 \u6297\u4f53\u7684\u8054\u5408\u6cbb\u7597\u7b56\u7565\u4e3a\u4eca\u540e\u7684\u80bf\u7624\u4e2a\u4f53\u5316<\/span>\u6cbb\u7597\u63d0\u4f9b\u4e86\u65b0\u601d\u8def\uff0c\u4f46\u5176\u534f\u540c\u673a\u5236\u53ca\u8054\u5408\u4f7f\u7528\u7684\u5408<\/span>\u7406\u6027\u5c1a\u5f85\u8fdb\u4e00\u6b65\u7814\u7a76\uff0c\u5e94\u8c28\u614e\u5bf9\u5f85\u3002<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u4e2d\u56fd\u65b0\u836f\u6742\u5fd7\uff0c2018 \u5e74\u7b2c27 \u5377\u7b2c4 \u671f<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u672c\u516c\u4f17\u53f7\u53d1\u5e03\u7684\u6587\u7ae0\u5747\u4e3a\u4fc3\u8fdb\u5236\u836f\u754c\u540c\u884c\u7684\u4ea4\u6d41\u4e0e\u5b66\u4e60\uff1b\u5185\u5bb9\u7531\u5c0f\u7f16\u67e5\u9605\u6587\u732e\u9009\u53d6\uff0c\u6392\u7248\u4e0e\u7f16\u8f91\u4e3a\u539f\u521b\u3002\u5982\u8f6c\u8f7d\uff0c\u8bf7\u6ce8\u660e\u6765\u6e90\u3002<\/p>\n

\u9009\u53d6\u7684\u6587\u7ae0\u5df2\u660e\u786e\u6ce8\u660e\u6765\u6e90\u548c\u4f5c\u8005\uff0c\u7248\u6743\u5f52\u539f\u4f5c\u8005\u6240\u6709\uff0c\u5982\u6d89\u53ca\u4f5c\u54c1\u5185\u5bb9\u3001\u7248\u6743\u6216\u5176\u4ed6\u95ee\u9898\uff0c\u8bf7\u8054\u7cfb\u6211\u4eec\u8fdb\u884c\u5220\u9664\u3002<\/strong><\/p>\n

\u6587\u7ae0\u5185\u5bb9\u4e3a\u4f5c\u8005\u89c2\u70b9\uff0c\u4e0d\u4ee3\u8868\u672c\u516c\u4f17\u53f7\u7acb\u573a\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u672c\u516c\u4f17\u53f7\u5f00\u901a\u5f80\u671f\u6587\u7ae0\u4efb\u610f\u641c\u529f\u80fd\u5566
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\u5728\u516c\u4f17\u53f7\u83dc\u5355\u680f\u4e2d\u8f93\u5165\u201c\u641c\u7d22\u201d\uff0c\u5373\u53ef\u641c\u7d22\u5f80\u671f\u5fae\u4fe1\u5185\u5bb9<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\"PD-1\/PD-L1<\/section>\n<\/section>\n<\/section>\n<\/section>\n


<\/p>\n<\/p><\/div>\n","protected":false},"excerpt":{"rendered":"

PD-1 \/PD-L1 \u6297\u4f53\u4e34\u5e8a\u836f\u7406\u5b66\u7814\u7a76\u7684\u8003\u8651 Consideration on clinical phar […]<\/p>\n","protected":false},"author":1,"featured_media":98393,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[1],"tags":[],"_links":{"self":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/98392"}],"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=98392"}],"version-history":[{"count":1,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/98392\/revisions"}],"predecessor-version":[{"id":98406,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/98392\/revisions\/98406"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/media\/98393"}],"wp:attachment":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/media?parent=98392"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/categories?post=98392"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/tags?post=98392"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}