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\u6d4e\u5357<\/span>2023\u5e7412\u67086\u65e5<\/span> \/\u7f8e\u901a\u793e\/ — 12\u67081\u81f33\u65e5\uff0c\u57282023\u5e74\u6b27\u6d32\u80bf\u7624\u5185\u79d1\u5b66\u4f1a\u4e9a\u6d32\u5e74\u4f1a\uff08ESMO Asia\uff09\u4e0a\uff0c\u9f50\u9c81\u5236\u836f\u4ee5\u58c1\u62a5\u5f62\u5f0f\u62a5\u544a\u4e861\u7c7b\u65b0\u836f\u827e\u5e15\u6d1b\u5229\u5355\u6297\uff08QL1604\uff09\u5355\u836f\u6cbb\u7597\u4e0d\u53ef\u5207\u9664\u6216\u8f6c\u79fb\u6027dMMR\/MSI-H\u5b9e\u4f53\u7624\u7684\u5355\u81c2\u3001II\u671f\u5173\u952e\u4e34\u5e8a\u7814\u7a76\u6700\u65b0\u7ed3\u679c\u3002\u4e3b\u8981\u7814\u7a76\u8005\u4e3a\u590d\u65e6\u5927\u5b66\u9644\u5c5e\u80bf\u7624\u533b\u9662\u90ed\u4f1f\u5251\u6559\u6388\u548c\u56db\u5ddd\u5927\u5b66\u534e\u897f\u533b\u9662\u6bd5\u950b\u6559\u6388\u3002<\/p>\n

\u827e\u5e15\u6d1b\u5229\u5355\u6297\u662f\u4e00\u79cd\u4e0ePD-1\u7ed3\u5408\u7684\u9ad8\u9009\u62e9\u6027\u4eba\u6e90\u5316\u5355\u514b\u9686\u6297\u4f53\u3002\u7814\u7a76\u7ed3\u679c\u663e\u793a\uff0c\u827e\u5e15\u6d1b\u5229\u5355\u6297\u5355\u836f\u6cbb\u7597\u4e0d\u53ef\u5207\u9664\u6216\u8f6c\u79fb\u6027dMMR\/MSI-H\u5b9e\u4f53\u7624\u5177\u6709\u826f\u597d\u7684\u7597\u6548\uff0c\u72ec\u7acb\u5f71\u50cf\u8bc4\u4f30\u59d4\u5458\u4f1a\uff08IRRC\uff09\u8bc4\u4f30\u7684\u5168\u4eba\u7fa4\u5ba2\u89c2\u7f13\u89e3\u7387\uff08ORR\uff09\u4e3a45.8%\uff0895%CI\uff0c 36.7-55.2\uff09\uff0c\u8d85\u8fc7\u9884\u8bbe\u4e3b\u8981\u7814\u7a76\u7ec8\u70b9\u3002<\/p>\n

\u4e00\u3001<\/b>\u7814\u7a76\u80cc\u666f<\/b><\/p>\n

DNA\u9519\u914d\u4fee\u590d\u7f3a\u9677\uff08dMMR\uff09\u6216\u9ad8\u5ea6\u5fae\u536b\u661f\u4e0d\u7a33\u5b9a\uff08MSI-H\uff09\u662f\u5b9e\u4f53\u7624\u7684\u72ec\u7279\u8868\u578b[1]<\/sup>\u3002DNA\u590d\u5236\u8fc7\u7a0b\u4e2d\uff0c\u5fae\u536b\u661f\u5e8f\u5217\u6700\u6613\u53d1\u751f\u9519\u914d\uff0c\u9700\u8981\u8fdb\u884c\u9519\u914d\u4fee\u590d\uff0cdMMR\u53ef\u5bfc\u81f4\u79fb\u7801\u7a81\u53d8\uff0c\u5f15\u8d77\u5fae\u536b\u661f\u4e0d\u7a33\u5b9a\uff08MSI\uff09\u3002dMMR\/MSI-H\u5b9e\u4f53\u7624\u5bf9\u514d\u75ab\u68c0\u67e5\u70b9\u6291\u5236\u5242\u6cbb\u7597\u53cd\u5e94\u826f\u597d\uff0c\u7a0b\u5e8f\u6027\u6b7b\u4ea1\u53d7\u4f53-1\uff08PD-1\uff09\u6216\u7a0b\u5e8f\u6027\u6b7b\u4ea1\u914d\u4f53-1\uff08PD-L1\uff09\u6291\u5236\u5242\u6cbb\u7597dMMR\/MSI-H\u5b9e\u4f53\u7624\u5177\u6709\u8f83\u9ad8\u7684\u5ba2\u89c2\u7f13\u89e3\u7387\uff08ORR\uff09\uff0c\u5e76\u4e14\u7f13\u89e3\u6301\u7eed\u65f6\u95f4\u957f[2-3]<\/sup>\u3002<\/p>\n

\u827e\u5e15\u6d1b\u5229\u5355\u6297\u6cbb\u7597\u665a\u671f\u5b9e\u4f53\u7624\u7684I\u671f\u7814\u7a76\u8868\u73b0\u51fa\u826f\u597d\u7684\u5b89\u5168\u6027\u548c\u6297\u80bf\u7624\u6d3b\u6027\uff0c\u5728\u63a5\u53d7\u827e\u5e15\u6d1b\u5229\u5355\u62970.3-3 mg\/kg Q3W\u7684\u6240\u6709\u60a3\u8005\u4e2d\uff0cORR\u8fbe\u523020%[4]<\/sup>\u3002\u672c\u5173\u952e\u7814\u7a76\u65e8\u5728\u8bc4\u4f30\u827e\u5e15\u6d1b\u5229\u5355\u6297\u5355\u836f\u6cbb\u7597\u4e0d\u53ef\u5207\u9664\u6216\u8f6c\u79fb\u6027dMMR\/MSI-H\u5b9e\u4f53\u7624\u7684\u7597\u6548\u548c\u5b89\u5168\u6027\u3002<\/p>\n

\u4e8c\u3001<\/b>\u7814\u7a76\u8bbe\u8ba1\u548c\u65b9\u6cd5<\/b><\/p>\n

\u672c\u7814\u7a76\u4e3a\u5355\u81c2\u3001II\u671f\u5173\u952e\u4e34\u5e8a\u7814\u7a76\uff0c\u7eb3\u5165\u4e0d\u53ef\u5207\u9664\u6216\u8f6c\u79fb\u6027\u7ecf\u7ec4\u7ec7\u75c5\u7406\u5b66\u6216\u7ec6\u80de\u5b66\u786e\u8ba4\u7684dMMR\/MSI-H\u5b9e\u4f53\u7624\u60a3\u8005\uff0c\u63a5\u53d7\u827e\u5e15\u6d1b\u5229\u5355\u6297\u5355\u836f\u6cbb\u7597\uff0c\u7ed9\u836f\u65b9\u6848\u4e3a200mg\u56fa\u5b9a\u5242\u91cf\uff08\u5982\u679c\u53d7\u8bd5\u8005\u4f53\u91cd\uff1c40kg\uff0c\u7ed9\u836f\u5242\u91cf\u4e3a3mg\/kg\uff09\uff0c\u9759\u8109\u6ef4\u6ce8\uff0c\u6bcf3\u5468\u7ed9\u836f1\u6b21\u3002\u60a3\u8005\u63a5\u53d7\u827e\u5e15\u6d1b\u5229\u5355\u6297\u6cbb\u7597\u76f4\u81f3\u75be\u75c5\u8fdb\u5c55\u3001\u51fa\u73b0\u4e0d\u53ef\u8010\u53d7\u7684\u6bd2\u6027\u3001\u5f00\u59cb\u65b0\u7684\u6297\u80bf\u7624\u6cbb\u7597\u3001\u6b7b\u4ea1\u3001\u64a4\u56de\u77e5\u60c5\u540c\u610f\u7b49\u539f\u56e0\uff0c\u6700\u957f\u6cbb\u7597\u65f6\u95f4\u4e0d\u8d85\u8fc72\u5e74\u3002\u6cbb\u7597\u7ed3\u675f\u540e\uff0c\u5bf9\u60a3\u8005\u8fdb\u884c\u751f\u5b58\u968f\u8bbf\u3002\u7814\u7a76\u7684\u4e3b\u8981\u7ec8\u70b9\u4e3aIRRC\u6839\u636e\u5b9e\u4f53\u80bf\u7624\u7597\u6548\u8bc4\u4ef7\u6807\u51c6\uff081.1\u7248\uff09\u8bc4\u4f30\u7684ORR\u3002\u7814\u7a76\u8bbe\u8ba1\u5982\u4e0b\u56fe\u6240\u793a\u3002<\/p>\n

\n

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\u4e09\u3001<\/b>\u7814\u7a76\u7ed3\u679c<\/b><\/p>\n

\u4ece2020\u5e746\u6708\u81f32023\u5e741\u6708\uff0c\u7814\u7a76\u5171\u7eb3\u5165120\u4f8bdMMR\/MSI-H\u5b9e\u4f53\u7624\u60a3\u8005\uff0c\u5176\u4e2d\u7ed3\u76f4\u80a0\u764c\u60a3\u800580\u4f8b\uff0866.7%\uff09\uff0c\u80c3\u764c\u60a3\u800518\u4f8b\uff0815.0%\uff09\uff0c\u5176\u5b83\u5b9e\u4f53\u7624\u60a3\u800522\u4f8b\uff0818.3%\uff09\uff1b97.5%\u7684\u60a3\u8005\u5728\u5165\u7ec4\u65f6\u75be\u75c5\u5206\u671f\u4e3aIV\u671f\uff0c\u4e2d\u4f4d\u6cbb\u7597\u7ebf\u6570\u4e3a2.0\uff08\u8303\u56f4\uff0c0\u20136\uff09\u3002<\/p>\n

\u5728\u7597\u6548\u65b9\u9762\uff0c\u622a\u81f32023\u5e747\u670820\u65e5\uff0c\u4e2d\u4f4d\u968f\u8bbf\u65f6\u95f4\u4e3a13.6\u4e2a\u6708\uff0c\u670911\u4f8b\u60a3\u8005\u8fbe\u5230\u5b8c\u5168\u7f13\u89e3\uff08CR\uff09\uff0c44\u4f8b\u60a3\u8005\u8fbe\u5230\u90e8\u5206\u7f13\u89e3\uff08PR\uff09\uff0cORR\u4e3a45.8%\uff0895% CI: 36.7%\u201355.2%\uff09\uff0c\u75be\u75c5\u63a7\u5236\u7387\uff08DCR\uff09\u4e3a77.5%\uff0895% CI: 69.0%\u201384.6%\uff09\u3002\u5728\u7ed3\u76f4\u80a0\u764c\u60a3\u8005\u4e2d\uff0cORR\u548cDCR\u5206\u522b\u4e3a42.5%\uff0895% CI: 31.5%\u201354.1%\uff09\u548c77.5%\uff0895% CI: 31.5%\u201354.1%\uff09\u3002\u4e2d\u4f4d\u7f13\u89e3\u6301\u7eed\u65f6\u95f4\uff08DoR\uff09\u5c1a\u672a\u8fbe\u5230\uff0c6\u4e2a\u6708\u548c12\u4e2a\u6708DoR\u7387\u5206\u522b\u4e3a100%\u548c97.4%\uff1b\u4e2d\u4f4d\u65e0\u8fdb\u5c55\u751f\u5b58\u671f\uff08PFS\uff09\u548c\u4e2d\u4f4d\u603b\u751f\u5b58\u671f\uff08OS\uff09\u672a\u8fbe\u5230\u3002\u7f13\u89e3\u60a3\u8005\u7684\u9776\u75c5\u7076\u6700\u4f73\u53d8\u5316\u60c5\u51b5\u5982\u4e0b\u56fe\u6240\u793a\u3002<\/p>\n

\n

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

\u56db\u3001<\/b>\u5c0f\u7ed3<\/b><\/p>\n

\u827e\u5e15\u6d1b\u5229\u5355\u6297\u5355\u836f\u6cbb\u7597\u4e0d\u53ef\u5207\u9664\u6216\u8f6c\u79fb\u6027dMMR\/MSI-H\u5b9e\u4f53\u7624\u5177\u6709\u826f\u597d\u7684\u7597\u6548\u548c\u5b89\u5168\u6027\u3002\u9f50\u9c81\u5236\u836f\u827e\u5e15\u6d1b\u5229\u5355\u6297\u4e0a\u5e02\u7533\u8bf7\u5df2\u4e8e\u4eca\u5e749\u6708\u83b7\u5f97CDE\u53d7\u7406\u3002<\/p>\n

\u53c2\u8003\u6587\u732e\uff1a<\/b><\/p>\n

1. Bhamidipati D, Subbiah V. Tumor-agnostic drug development in dMMR\/MSI-H solid tumors. Trends Cancer. 2023;9(10):828-839.
2. Le DT, et al. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med. 2015;372(26):2509-20.
3. Li J, et al. Subcutaneous envafolimab monotherapy in patients with advanced defective mismatch repair\/microsatellite instability high solid tumors. J Hematol Oncol. 2021;14(1):95.
4. Huang Z, et al. A first-in-human, open-label, dose-escalation and dose-expansion phase I study to evaluate the safety, tolerability, pharmacokinetics\/pharmacodynamics, and antitumor activity of QL1604, a humanized anti-PD-1 mAb, in patients with advanced or metastatic solid tumors. Front Immunol. 2023;14:1258573.<\/p>\n

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Bhamidipati D, Subbiah V. Tumor-agnostic drug development in dMMR\/MSI-H solid tumors. Trends Cancer. 2023;9(10):828-839.2. Le DT, et al. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. 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