{"id":282953,"date":"2024-12-10T22:15:00","date_gmt":"2024-12-10T14:15:00","guid":{"rendered":"https:\/\/pingtungtimes.com.tw\/?p=282953"},"modified":"2024-12-10T22:15:00","modified_gmt":"2024-12-10T14:15:00","slug":"%e3%80%90%e7%9b%b4%e6%93%8aash-2024%e3%80%91%e6%96%ac%e7%8d%b2%e6%91%98%e8%a6%81%e6%88%90%e5%b0%b1%e7%8d%8e%ef%bc%81%e8%80%90%e7%ab%8b%e5%85%8b%e8%81%af%e5%90%88bcl-2%e6%8a%91%e5%88%b6%e5%8a%91a","status":"publish","type":"post","link":"https:\/\/pingtungtimes.com.tw\/?p=282953","title":{"rendered":"\u3010\u76f4\u64caASH 2024\u3011\u65ac\u7372\u6458\u8981\u6210\u5c31\u734e\uff01\u8010\u7acb\u514b\u00ae\u806f\u5408Bcl-2\u6291\u5236\u5291APG-2575\u6578\u64da\u9996\u6b21\u516c\u4f48\uff0c\u7121\u5316\u7642\u6cbb\u7642\u5152\u7ae5R\/R Ph+ ALL\u8868\u73fe\u512a\u7570"},"content":{"rendered":"<div>\n<table name=\"logo_release\" border=\"0\" cellspacing=\"10\" cellpadding=\"5\" align=\"right\">\n<tbody>\n<tr>\n<td><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p><span 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id=\"DivAssetPlaceHolder1\">\n<\/p><\/div>\n<p>ASH\u5e74\u6703\u662f\u5168\u7403\u8840\u6db2\u5b78\u9818\u57df\u898f\u6a21\u6700\u5927\u7684\u570b\u969b\u5b78\u8853\u76db\u6703\u4e4b\u4e00\uff0c\u5f59\u96c6\u4e86\u6700\u524d\u6cbf\u7684\u7814\u7a76\u9032\u5c55\u53ca\u6700\u65b0\u7684\u85e5\u7269\u7814\u767c\u6578\u64da\uff0c\u5c55\u793a\u5168\u7403\u8840\u6db2\u5b78\u9818\u57df\u7684\u6700\u9ad8\u5b78\u8853\u6c34\u5e73\u3002\u4f5c\u70ba\u65e5\u76ca\u6d3b\u8e8d\u5728\u570b\u969b\u5b78\u8853\u821e\u53f0\u4e0a\u7684\u300c\u4e2d\u570b\u8072\u97f3\u300d\uff0c\u4eca\u5e74\u4e9e\u76db\u91ab\u85e5\u56db\u500b\u54c1\u7a2e\uff08\u8010\u7acb\u514b<sup>\u00ae<\/sup>\u3001APG-2575\u3001APG-2449\u3001APG-5918\uff09\u6709\u591a\u9805\u81e8\u5e8a\u548c\u81e8\u5e8a\u524d\u9032\u5c55\u5165\u9078ASH\u5e74\u6703\u5c55\u793a\u53ca\u5831\u544a\uff0c\u5176\u4e2d\u5169\u9805\u7372\u53e3\u982d\u5831\u544a\u3002<\/p>\n<p>\u9019\u9805\u91dd\u5c0dR\/R Ph+ ALL\u5152\u7ae5\u53ca\u9752\u5c11\u5e74\u60a3\u8005\u7684\u7814\u7a76\u6578\u64da\u521d\u6b65\u9a57\u8b49\u4e86\u5967\u96f7\u5df4\u66ff\u5c3c\u8207APG-2575\u806f\u5408\u6cbb\u7642\u7684\u7642\u6548\u6f5b\u529b\u548c\u5b89\u5168\u6027\u512a\u52e2\u3002\u6578\u64da\u986f\u793a\uff0c\u8a72\u65b9\u6848\u5728\u7121\u9700\u5f37\u5316\u7642\u6216\u514d\u75ab\u6cbb\u7642\u7684\u60c5\u6cc1\u4e0b\uff0c\u5be6\u73fe\u4e8683.3%\u7684\u5b8c\u5168\u7de9\u89e3\uff08CR\uff09\u7387\u548c71.4%\u7684\u53ef\u6e2c\u91cf\u6b98\u7559\u75be\u75c5\uff08MRD\uff09\u8f49\u9670\u7387\u3002<\/p>\n<p>\u8010\u7acb\u514b<sup>\u00ae<\/sup>\u662f\u4e2d\u570b\u9996\u500b\u7372\u6279\u4e0a\u5e02\u7684\u7b2c\u4e09\u4ee3BCR-ABL\u6291\u5236\u5291\uff0c\u8a72\u54c1\u7a2e\u5df2\u7372\u6279\u7528\u65bc\u6cbb\u7642\u4efb\u4f55TKI\u8010\u85e5\uff0c\u4e26\u4f34\u6709T315I\u7a81\u8b8a\u7684CML-CP\u6216CML-\u52a0\u901f\u671f\uff08-AP\uff09\u7684\u6210\u5e74\u60a3\u8005\uff1b\u4ee5\u53ca\u5c0d\u4e00\u4ee3\u548c\u4e8c\u4ee3TKI\u8010\u85e5\u548c\/\u6216\u4e0d\u8010\u53d7\u7684CML-CP\u6210\u5e74\u60a3\u8005\u3002\u8010\u7acb\u514b<sup>\u00ae<\/sup>\u5728\u4e2d\u570b\u7684\u5546\u696d\u5316\u63a8\u5ee3\u7531\u4e9e\u76db\u91ab\u85e5\u548c\u4fe1\u9054\u751f\u7269\u5171\u540c\u8ca0\u8cac\u3002<\/p>\n<p><b>\u8a72\u9805\u81e8\u5e8a\u7814\u7a76\u7684\u4e3b\u8981\u7814\u7a76\u8005\u3001\u4e2d\u570b\u91ab\u5b78\u79d1\u5b78\u9662\u8840\u6db2\u75c5\u91ab\u9662\u7afa\u66c9\u51e1\u6559\u6388<\/b>\u8868\u793a\uff1a\u300c\u8fd1\u5e74\u4f86\u6211\u570b\u5152\u7ae5\u8840\u6db2\u75c5\u6574\u9ad4\u8a3a\u6cbb\u6c34\u5e73\u5df2\u6709\u5927\u5e45\u63d0\u5347\uff0c\u4f46\u662f\u5728Ph+ ALL\u9818\u57df\uff0c\u56e0\u70ba\u5176\u75be\u75c5\u7684\u7279\u6b8a\u6027\uff0c\u6574\u9ad4\u9810\u5f8c\u4f9d\u7136\u8f03\u5dee\uff0cR\/R Ph+ ALL\u6cbb\u7642\u4ecd\u6709\u5f88\u5927\u7684\u63a2\u7d22\u7a7a\u9593\u3002\u73fe\u5728\u7b2c\u4e09\u4ee3BCR-ABL1\u6291\u5236\u5291\u5967\u96f7\u5df4\u66ff\u5c3c\u806f\u5408Bcl-2\u6291\u5236\u5291APG-2575\u7684\u7814\u7a76\u7684\u521d\u6b65\u6578\u64da\u63d0\u793a\uff0c\u5728\u7121\u9700\u5f37\u5316\u7642\u6216\u514d\u75ab\u6cbb\u7642\u7684\u60c5\u6cc1\u4e0b\uff0c\u60a3\u5152\u53ef\u4ee5\u7372\u5f97\u76f8\u7576\u4e0d\u932f\u7684\u5b8c\u5168\u7de9\u89e3\u7387\u548c\u6b98\u7559\u75be\u75c5\u8f49\u9670\u7387\uff0c\u4e14\u8010\u53d7\u6027\u826f\u597d\u3002\u6211\u5011\u671f\u5f85\u5728\u63a5\u4e0b\u4f86\u7684\u81e8\u5e8a\u7814\u7a76\u4e2d\u9032\u4e00\u6b65\u78ba\u5b9a\u5169\u85e5\u806f\u5408\u7684\u5408\u9069\u5291\u91cf\u548c\u65b9\u6848\u3002\u70baR\/R Ph+ ALL\u5152\u7ae5\u60a3\u8005\uff0c\u63a2\u7d22\u66f4\u591a\u5b89\u5168\u4e14\u6709\u6548\u7684\u6cbb\u7642\u9078\u64c7\u3002\u300d<\/p>\n<p><b>\u4e9e\u76db\u91ab\u85e5\u9996\u5e2d\u91ab\u5b78\u5b98\u7fdf\u4e00\u5e06\u535a\u58eb<\/b>\u8868\u793a\uff1a\u300c\u9019\u662f\u516c\u53f8\u5169\u500b\u91cd\u78c5\u54c1\u7a2e\u8010\u7acb\u514b<sup>\u00ae<\/sup>\u548cAPG-2575\u7684\u9996\u6b21\u806f\u7528\u3002\u5728\u9019\u4e00\u6cbb\u7642\u65b9\u6848\u4e2d\uff0cPh+ ALL\u5152\u7ae5\u60a3\u8005\u5728\u7121\u5316\u7642\u7684\u60c5\u6cc1\u4e0b\u4ecd\u7372\u5f97\u5353\u8d8a\u7684\u7642\u6548\u548c\u5b89\u5168\u6027\uff0c\u8d77\u6548\u8fc5\u901f\uff0c\u7de9\u89e3\u7387\u9ad8\u4e14\u7de9\u89e3\u7a0b\u5ea6\u6df1\u3002\u9019\u610f\u5473\u8457\u8a72\u806f\u5408\u6cbb\u7642\u65b9\u6848\u6709\u671b\u6210\u70baPh+ ALL\u9032\u5165\u300e\u7121\u5316\u7642\u300f\u6642\u4ee3\u7684\u65b0\u7684\u6cbb\u7642\u9078\u64c7\u3002\u672a\u4f86\uff0c\u6211\u5011\u5c07\u7e7c\u7e8c\u5805\u5b88\u300e\u89e3\u6c7a\u4e2d\u570b\u4e43\u81f3\u5168\u7403\u60a3\u8005\u5c1a\u672a\u6eff\u8db3\u7684\u81e8\u5e8a\u9700\u6c42\u300f\u9019\u4e00\u4f7f\u547d\uff0c\u52a0\u901f\u63a8\u9032\u516c\u53f8\u91cd\u9ede\u54c1\u7a2e\u5728\u5168\u7403\u5c64\u9762\u7684\u81e8\u5e8a\u958b\u767c\uff0c\u8b93\u66f4\u591a\u5b89\u5168\u6709\u6548\u7684\u85e5\u7269\u76e1\u5feb\u4e0a\u5e02\uff0c\u65e9\u65e5\u60e0\u53ca\u60a3\u8005\u3002\u300d<\/p>\n<p>\u6b64\u9805\u7814\u7a76\u57282024 ASH\u5e74\u6703\u4e0a\u5c55\u793a\u7684\u6838\u5fc3\u8981\u9ede\u5982\u4e0b\uff1a<\/p>\n<p><b>Safety and Efficacy of Olverembatinib (HQP1351) Combined with Lisaftoclax (APG-2575) in Children and Adolescents with Relapsed\/Refractory Philadelphia Chromosome\u2013Positive Acute Lymphoblastic Leukemia (R\/R Ph+ ALL): First Report from a Phase 1 Study<\/b><br 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\/><u>\u7814\u7a76\u80cc\u666f<\/u>\uff1a\u5967\u96f7\u5df4\u66ff\u5c3c\u662f\u65b0\u578b\u4e09\u4ee3TKI\uff0c\u5177\u6709\u826f\u597d\u8010\u53d7\u6027\uff0c\u4e26\u5728\u5df2\u63a5\u53d7\u6df1\u5ea6\u6cbb\u7642\u7684CP-CML\u60a3\u8005\u4e2d\uff08\u7121\u8ad6\u662f\u5426\u6709T315I\u7a81\u8b8a\uff09\u8868\u73fe\u51fa\u5f37\u5927\u4e14\u6301\u4e45\u7684\u6297\u767d\u8840\u75c5\u6d3b\u6027\u3002Lisaftoclax\u662f\u4e00\u7a2e\u65b0\u578bBcl-2\u6291\u5236\u5291\uff0c\u5728\u591a\u7a2e\u8840\u6db2\u60e1\u6027\u816b\u7624\u4e2d\u986f\u793a\u51fa\u6297\u816b\u7624\u6548\u679c\u3002\u76ee\u524d\uff0cR\/R Ph+ ALL\u5152\u7ae5\u60a3\u8005\u5c1a\u7121\u6709\u6548\u6cbb\u7642\u9078\u64c7\u3002<\/p>\n<p><u>\u7814\u7a76\u4ecb\u7d39<\/u>\uff1a\u672c\u7814\u7a76\u65e8\u5728\u63a2\u7d22\u5967\u96f7\u5df4\u66ff\u5c3c\u55ae\u85e5\u6216\u806f\u5408Lisaftoclax\u5728R\/R Ph+ ALL\u5152\u7ae5\u60a3\u8005\u4e2d\u7684\u5b89\u5168\u6027\u3001\u6709\u6548\u6027\u53ca\u85e5\u4ee3\u52d5\u529b\u5b78\uff08PK\uff09\u7279\u5fb5\u3002<\/p>\n<p><u>\u5165\u7d44\u60a3\u8005\u548c\u7814\u7a76\u65b9\u6cd5<\/u>\uff1a<\/p>\n<ul type=\"disc\">\n<li>\u9019\u662f\u4e00\u9805\u958b\u653e\u6a19\u7c64\u7684Ib\u671f\u7814\u7a76\uff0c\u5165\u7d44\u7684\u70ba\u5e74\u9f61\u5c0f\u65bc18\u6b72\u7684R\/R Ph+ ALL\u5152\u7ae5\u60a3\u8005\uff0c\u9019\u4e9b\u60a3\u8005\u5c0d\u81f3\u5c11\u4e00\u7a2eTKI\u8010\u85e5\u6216\u4e0d\u8010\u53d7\uff08\u5982\u679c\u60a3\u8005\u651c\u5e36T315I\u7a81\u8b8a\uff0c\u5247\u4e0d\u8003\u616e\u65e2\u5f80TKI\u4f7f\u7528\u60c5\u6cc1\uff09\u3002\u60a3\u8005\u9700\u5177\u5099\u8db3\u5920\u7684Karnofsky\/Lansky\u529f\u80fd\u72c0\u614b\u8a55\u5206\u548c\u5668\u5b98\u529f\u80fd\u3002\u60a3\u6709\u8207Ph+ ALL\u7121\u95dc\u7684\u75c7\u72c0\u6027\u4e2d\u6a1e\u795e\u7d93\u7cfb\u7d71\u75be\u75c5\u6216\u986f\u8457\u51fa\u8840\u7684\u60a3\u8005\u88ab\u6392\u9664\u5728\u5916\u3002<\/li>\n<li>\u5967\u96f7\u5df4\u66ff\u5c3c\u4ee5\u6210\u4eba\u7b49\u6548\u5291\u91cf\uff08AED\uff0940 mg\u53e3\u670d\uff0c\u9694\u65e5\u4e00\u6b21\uff0c\u6301\u7e8c2\u5468\uff08\u7b2c1-14\u5929\uff09\u3002\u7136\u5f8c\u540c\u5291\u91cf\u7684\u5967\u96f7\u5df4\u66ff\u5c3c\u806f\u5408Lisaftoclax\uff0c\u5f8c\u8005\u7684\u6307\u5b9a\u5291\u91cf\u70ba200\/400\/600 mg\uff08AED\uff09\uff0c\u6bcf\u65e5\u4e00\u6b21\uff08QD\uff09\uff0c\u7b2c13-42\u5929\uff08\u7b2c13-15\u5929\u97003\u5929\u5291\u91cf\u905e\u589e\uff09\u3002\u5730\u585e\u7c73\u677e\u4ee56 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name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/pingtungtimes.com.tw\/?p=282953\" \/>\n<meta property=\"og:locale\" content=\"zh_TW\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"\u3010\u76f4\u64caASH 2024\u3011\u65ac\u7372\u6458\u8981\u6210\u5c31\u734e\uff01\u8010\u7acb\u514b\u00ae\u806f\u5408Bcl-2\u6291\u5236\u5291APG-2575\u6578\u64da\u9996\u6b21\u516c\u4f48\uff0c\u7121\u5316\u7642\u6cbb\u7642\u5152\u7ae5R\/R Ph+ ALL\u8868\u73fe\u512a\u7570 - \u5c4f\u6771\u6642\u5831\u96fb\u5b50\u5831\" \/>\n<meta property=\"og:description\" content=\"\u7f8e\u570b\u99ac\u91cc\u862d\u5dde\u7f85\u514b\u7dad\u723e\u5e02\u548c\u4e2d\u570b\u8607\u5dde2024\u5e7412\u670810\u65e5 \/\u7f8e\u901a\u793e\/ -- \u81f4\u529b\u65bc\u5728\u816b\u7624\u7b49\u9818\u57df\u958b\u767c\u5275\u65b0\u85e5\u7269\u7684\u9818\u5148\u7684\u751f\u7269\u91ab\u85e5\u4f01\u696d\u2014\u2014\u4e9e\u76db\u91ab\u85e5\uff086855.HK\uff09\u4eca\u65e5\u5ba3\u4f48\uff0c\u516c\u53f8\u5df2\u5728\u7f8e\u570b\u8056\u5730\u4e9e\u54e5\u8209\u8fa6\u7684\u7b2c66\u5c46\u7f8e\u570b\u8840\u6db2\u5b78\u6703\uff08American Society of Hematology\uff0cASH\uff09\u5e74\u6703\u4e0a\uff0c\u4ee5\u58c1\u5831\u5c55\u793a\u5f62\u5f0f\u516c\u4f48\u4e86\u516c\u53f8\u539f\u52751\u985e\u65b0\u85e5\u5967\u96f7\u5df4\u66ff\u5c3c\uff08\u7814\u767c\u4ee3\u865f\uff1aHQP1351\uff1b\u5546\u54c1\u540d\uff1a\u8010\u7acb\u514b\u00ae\uff09\u806f\u5408\u516c\u53f8\u539f\u7814Bcl-2\u6291\u5236\u5291APG-2575\u6cbb\u7642\u5fa9\u767c\/\u96e3\u6cbb\u6027\u8cbb\u57ce\u67d3\u8272\u9ad4\u967d\u6027\u6025\u6027\u6dcb\u5df4\u7d30\u80de\u767d\u8840\u75c5\uff08R\/R Ph+ ALL\uff09\u5152\u7ae5\u53ca\u9752\u5c11\u5e74\u60a3\u8005\u7684\u5b89\u5168\u6027\u548c\u7642\u6548\u6578\u64da\u3002\u9019\u662f\u4e9e\u76db\u91ab\u85e5\u5169\u500b\u91cd\u78c5\u54c1\u7a2e\u806f\u5408\u6cbb\u7642\u6578\u64da\u7684\u9996\u6b21\u62ab\u9732\uff0c\u4e26\u69ae\u7372\u672c\u5c46ASH\u5e74\u6703\u7684\u300c\u6458\u8981\u6210\u5c31\u734e\u300d\u3002     ASH\u5e74\u6703\u662f\u5168\u7403\u8840\u6db2\u5b78\u9818\u57df\u898f\u6a21\u6700\u5927\u7684\u570b\u969b\u5b78\u8853\u76db\u6703\u4e4b\u4e00\uff0c\u5f59\u96c6\u4e86\u6700\u524d\u6cbf\u7684\u7814\u7a76\u9032\u5c55\u53ca\u6700\u65b0\u7684\u85e5\u7269\u7814\u767c\u6578\u64da\uff0c\u5c55\u793a\u5168\u7403\u8840\u6db2\u5b78\u9818\u57df\u7684\u6700\u9ad8\u5b78\u8853\u6c34\u5e73\u3002\u4f5c\u70ba\u65e5\u76ca\u6d3b\u8e8d\u5728\u570b\u969b\u5b78\u8853\u821e\u53f0\u4e0a\u7684\u300c\u4e2d\u570b\u8072\u97f3\u300d\uff0c\u4eca\u5e74\u4e9e\u76db\u91ab\u85e5\u56db\u500b\u54c1\u7a2e\uff08\u8010\u7acb\u514b\u00ae\u3001APG-2575\u3001APG-2449\u3001APG-5918\uff09\u6709\u591a\u9805\u81e8\u5e8a\u548c\u81e8\u5e8a\u524d\u9032\u5c55\u5165\u9078ASH\u5e74\u6703\u5c55\u793a\u53ca\u5831\u544a\uff0c\u5176\u4e2d\u5169\u9805\u7372\u53e3\u982d\u5831\u544a\u3002 \u9019\u9805\u91dd\u5c0dR\/R Ph+ ALL\u5152\u7ae5\u53ca\u9752\u5c11\u5e74\u60a3\u8005\u7684\u7814\u7a76\u6578\u64da\u521d\u6b65\u9a57\u8b49\u4e86\u5967\u96f7\u5df4\u66ff\u5c3c\u8207APG-2575\u806f\u5408\u6cbb\u7642\u7684\u7642\u6548\u6f5b\u529b\u548c\u5b89\u5168\u6027\u512a\u52e2\u3002\u6578\u64da\u986f\u793a\uff0c\u8a72\u65b9\u6848\u5728\u7121\u9700\u5f37\u5316\u7642\u6216\u514d\u75ab\u6cbb\u7642\u7684\u60c5\u6cc1\u4e0b\uff0c\u5be6\u73fe\u4e8683.3%\u7684\u5b8c\u5168\u7de9\u89e3\uff08CR\uff09\u7387\u548c71.4%\u7684\u53ef\u6e2c\u91cf\u6b98\u7559\u75be\u75c5\uff08MRD\uff09\u8f49\u9670\u7387\u3002 \u8010\u7acb\u514b\u00ae\u662f\u4e2d\u570b\u9996\u500b\u7372\u6279\u4e0a\u5e02\u7684\u7b2c\u4e09\u4ee3BCR-ABL\u6291\u5236\u5291\uff0c\u8a72\u54c1\u7a2e\u5df2\u7372\u6279\u7528\u65bc\u6cbb\u7642\u4efb\u4f55TKI\u8010\u85e5\uff0c\u4e26\u4f34\u6709T315I\u7a81\u8b8a\u7684CML-CP\u6216CML-\u52a0\u901f\u671f\uff08-AP\uff09\u7684\u6210\u5e74\u60a3\u8005\uff1b\u4ee5\u53ca\u5c0d\u4e00\u4ee3\u548c\u4e8c\u4ee3TKI\u8010\u85e5\u548c\/\u6216\u4e0d\u8010\u53d7\u7684CML-CP\u6210\u5e74\u60a3\u8005\u3002\u8010\u7acb\u514b\u00ae\u5728\u4e2d\u570b\u7684\u5546\u696d\u5316\u63a8\u5ee3\u7531\u4e9e\u76db\u91ab\u85e5\u548c\u4fe1\u9054\u751f\u7269\u5171\u540c\u8ca0\u8cac\u3002 \u8a72\u9805\u81e8\u5e8a\u7814\u7a76\u7684\u4e3b\u8981\u7814\u7a76\u8005\u3001\u4e2d\u570b\u91ab\u5b78\u79d1\u5b78\u9662\u8840\u6db2\u75c5\u91ab\u9662\u7afa\u66c9\u51e1\u6559\u6388\u8868\u793a\uff1a\u300c\u8fd1\u5e74\u4f86\u6211\u570b\u5152\u7ae5\u8840\u6db2\u75c5\u6574\u9ad4\u8a3a\u6cbb\u6c34\u5e73\u5df2\u6709\u5927\u5e45\u63d0\u5347\uff0c\u4f46\u662f\u5728Ph+ ALL\u9818\u57df\uff0c\u56e0\u70ba\u5176\u75be\u75c5\u7684\u7279\u6b8a\u6027\uff0c\u6574\u9ad4\u9810\u5f8c\u4f9d\u7136\u8f03\u5dee\uff0cR\/R Ph+ ALL\u6cbb\u7642\u4ecd\u6709\u5f88\u5927\u7684\u63a2\u7d22\u7a7a\u9593\u3002\u73fe\u5728\u7b2c\u4e09\u4ee3BCR-ABL1\u6291\u5236\u5291\u5967\u96f7\u5df4\u66ff\u5c3c\u806f\u5408Bcl-2\u6291\u5236\u5291APG-2575\u7684\u7814\u7a76\u7684\u521d\u6b65\u6578\u64da\u63d0\u793a\uff0c\u5728\u7121\u9700\u5f37\u5316\u7642\u6216\u514d\u75ab\u6cbb\u7642\u7684\u60c5\u6cc1\u4e0b\uff0c\u60a3\u5152\u53ef\u4ee5\u7372\u5f97\u76f8\u7576\u4e0d\u932f\u7684\u5b8c\u5168\u7de9\u89e3\u7387\u548c\u6b98\u7559\u75be\u75c5\u8f49\u9670\u7387\uff0c\u4e14\u8010\u53d7\u6027\u826f\u597d\u3002\u6211\u5011\u671f\u5f85\u5728\u63a5\u4e0b\u4f86\u7684\u81e8\u5e8a\u7814\u7a76\u4e2d\u9032\u4e00\u6b65\u78ba\u5b9a\u5169\u85e5\u806f\u5408\u7684\u5408\u9069\u5291\u91cf\u548c\u65b9\u6848\u3002\u70baR\/R Ph+ ALL\u5152\u7ae5\u60a3\u8005\uff0c\u63a2\u7d22\u66f4\u591a\u5b89\u5168\u4e14\u6709\u6548\u7684\u6cbb\u7642\u9078\u64c7\u3002\u300d \u4e9e\u76db\u91ab\u85e5\u9996\u5e2d\u91ab\u5b78\u5b98\u7fdf\u4e00\u5e06\u535a\u58eb\u8868\u793a\uff1a\u300c\u9019\u662f\u516c\u53f8\u5169\u500b\u91cd\u78c5\u54c1\u7a2e\u8010\u7acb\u514b\u00ae\u548cAPG-2575\u7684\u9996\u6b21\u806f\u7528\u3002\u5728\u9019\u4e00\u6cbb\u7642\u65b9\u6848\u4e2d\uff0cPh+ ALL\u5152\u7ae5\u60a3\u8005\u5728\u7121\u5316\u7642\u7684\u60c5\u6cc1\u4e0b\u4ecd\u7372\u5f97\u5353\u8d8a\u7684\u7642\u6548\u548c\u5b89\u5168\u6027\uff0c\u8d77\u6548\u8fc5\u901f\uff0c\u7de9\u89e3\u7387\u9ad8\u4e14\u7de9\u89e3\u7a0b\u5ea6\u6df1\u3002\u9019\u610f\u5473\u8457\u8a72\u806f\u5408\u6cbb\u7642\u65b9\u6848\u6709\u671b\u6210\u70baPh+ ALL\u9032\u5165\u300e\u7121\u5316\u7642\u300f\u6642\u4ee3\u7684\u65b0\u7684\u6cbb\u7642\u9078\u64c7\u3002\u672a\u4f86\uff0c\u6211\u5011\u5c07\u7e7c\u7e8c\u5805\u5b88\u300e\u89e3\u6c7a\u4e2d\u570b\u4e43\u81f3\u5168\u7403\u60a3\u8005\u5c1a\u672a\u6eff\u8db3\u7684\u81e8\u5e8a\u9700\u6c42\u300f\u9019\u4e00\u4f7f\u547d\uff0c\u52a0\u901f\u63a8\u9032\u516c\u53f8\u91cd\u9ede\u54c1\u7a2e\u5728\u5168\u7403\u5c64\u9762\u7684\u81e8\u5e8a\u958b\u767c\uff0c\u8b93\u66f4\u591a\u5b89\u5168\u6709\u6548\u7684\u85e5\u7269\u76e1\u5feb\u4e0a\u5e02\uff0c\u65e9\u65e5\u60e0\u53ca\u60a3\u8005\u3002\u300d \u6b64\u9805\u7814\u7a76\u57282024 ASH\u5e74\u6703\u4e0a\u5c55\u793a\u7684\u6838\u5fc3\u8981\u9ede\u5982\u4e0b\uff1a Safety and Efficacy of Olverembatinib (HQP1351) Combined with Lisaftoclax (APG-2575) in Children and Adolescents with Relapsed\/Refractory Philadelphia Chromosome\u2013Positive Acute Lymphoblastic Leukemia (R\/R Ph+ ALL): First Report from a Phase 1 Study\u5967\u96f7\u5df4\u66ff\u5c3c\uff08HQP1351\uff09\u806f\u5408Lisaftoclax\uff08APG-2575\uff09\u6cbb\u7642\u5fa9\u767c\/\u96e3\u6cbb\u6027\u8cbb\u57ce\u67d3\u8272\u9ad4\u967d\u6027\u6025\u6027\u6dcb\u5df4\u7d30\u80de\u767d\u8840\u75c5\uff08R\/R Ph+ ALL\uff09\u5152\u7ae5\u53ca\u9752\u5c11\u5e74\u60a3\u8005\u7684\u5b89\u5168\u6027\u548c\u7642\u6548\uff1a\u4e00\u9805I\u671f\u81e8\u5e8a\u7814\u7a76\u7684\u9996\u6b21\u5831\u544a\u5c55\u793a\u5f62\u5f0f\uff1a\u58c1\u5831\u5c55\u793a\u6458\u8981\u7de8\u865f\uff1a1443\u5206\u6703\u5834\uff1a613. 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ALL\uff09\u5152\u7ae5\u53ca\u9752\u5c11\u5e74\u60a3\u8005\u7684\u5b89\u5168\u6027\u548c\u7642\u6548\u6578\u64da\u3002\u9019\u662f\u4e9e\u76db\u91ab\u85e5\u5169\u500b\u91cd\u78c5\u54c1\u7a2e\u806f\u5408\u6cbb\u7642\u6578\u64da\u7684\u9996\u6b21\u62ab\u9732\uff0c\u4e26\u69ae\u7372\u672c\u5c46ASH\u5e74\u6703\u7684\u300c\u6458\u8981\u6210\u5c31\u734e\u300d\u3002 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ALL\u5152\u7ae5\u53ca\u9752\u5c11\u5e74\u60a3\u8005\u7684\u7814\u7a76\u6578\u64da\u521d\u6b65\u9a57\u8b49\u4e86\u5967\u96f7\u5df4\u66ff\u5c3c\u8207APG-2575\u806f\u5408\u6cbb\u7642\u7684\u7642\u6548\u6f5b\u529b\u548c\u5b89\u5168\u6027\u512a\u52e2\u3002\u6578\u64da\u986f\u793a\uff0c\u8a72\u65b9\u6848\u5728\u7121\u9700\u5f37\u5316\u7642\u6216\u514d\u75ab\u6cbb\u7642\u7684\u60c5\u6cc1\u4e0b\uff0c\u5be6\u73fe\u4e8683.3%\u7684\u5b8c\u5168\u7de9\u89e3\uff08CR\uff09\u7387\u548c71.4%\u7684\u53ef\u6e2c\u91cf\u6b98\u7559\u75be\u75c5\uff08MRD\uff09\u8f49\u9670\u7387\u3002 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ALL\u6cbb\u7642\u4ecd\u6709\u5f88\u5927\u7684\u63a2\u7d22\u7a7a\u9593\u3002\u73fe\u5728\u7b2c\u4e09\u4ee3BCR-ABL1\u6291\u5236\u5291\u5967\u96f7\u5df4\u66ff\u5c3c\u806f\u5408Bcl-2\u6291\u5236\u5291APG-2575\u7684\u7814\u7a76\u7684\u521d\u6b65\u6578\u64da\u63d0\u793a\uff0c\u5728\u7121\u9700\u5f37\u5316\u7642\u6216\u514d\u75ab\u6cbb\u7642\u7684\u60c5\u6cc1\u4e0b\uff0c\u60a3\u5152\u53ef\u4ee5\u7372\u5f97\u76f8\u7576\u4e0d\u932f\u7684\u5b8c\u5168\u7de9\u89e3\u7387\u548c\u6b98\u7559\u75be\u75c5\u8f49\u9670\u7387\uff0c\u4e14\u8010\u53d7\u6027\u826f\u597d\u3002\u6211\u5011\u671f\u5f85\u5728\u63a5\u4e0b\u4f86\u7684\u81e8\u5e8a\u7814\u7a76\u4e2d\u9032\u4e00\u6b65\u78ba\u5b9a\u5169\u85e5\u806f\u5408\u7684\u5408\u9069\u5291\u91cf\u548c\u65b9\u6848\u3002\u70baR\\\/R Ph+ ALL\u5152\u7ae5\u60a3\u8005\uff0c\u63a2\u7d22\u66f4\u591a\u5b89\u5168\u4e14\u6709\u6548\u7684\u6cbb\u7642\u9078\u64c7\u3002\u300d \u4e9e\u76db\u91ab\u85e5\u9996\u5e2d\u91ab\u5b78\u5b98\u7fdf\u4e00\u5e06\u535a\u58eb\u8868\u793a\uff1a\u300c\u9019\u662f\u516c\u53f8\u5169\u500b\u91cd\u78c5\u54c1\u7a2e\u8010\u7acb\u514b\u00ae\u548cAPG-2575\u7684\u9996\u6b21\u806f\u7528\u3002\u5728\u9019\u4e00\u6cbb\u7642\u65b9\u6848\u4e2d\uff0cPh+ ALL\u5152\u7ae5\u60a3\u8005\u5728\u7121\u5316\u7642\u7684\u60c5\u6cc1\u4e0b\u4ecd\u7372\u5f97\u5353\u8d8a\u7684\u7642\u6548\u548c\u5b89\u5168\u6027\uff0c\u8d77\u6548\u8fc5\u901f\uff0c\u7de9\u89e3\u7387\u9ad8\u4e14\u7de9\u89e3\u7a0b\u5ea6\u6df1\u3002\u9019\u610f\u5473\u8457\u8a72\u806f\u5408\u6cbb\u7642\u65b9\u6848\u6709\u671b\u6210\u70baPh+ ALL\u9032\u5165\u300e\u7121\u5316\u7642\u300f\u6642\u4ee3\u7684\u65b0\u7684\u6cbb\u7642\u9078\u64c7\u3002\u672a\u4f86\uff0c\u6211\u5011\u5c07\u7e7c\u7e8c\u5805\u5b88\u300e\u89e3\u6c7a\u4e2d\u570b\u4e43\u81f3\u5168\u7403\u60a3\u8005\u5c1a\u672a\u6eff\u8db3\u7684\u81e8\u5e8a\u9700\u6c42\u300f\u9019\u4e00\u4f7f\u547d\uff0c\u52a0\u901f\u63a8\u9032\u516c\u53f8\u91cd\u9ede\u54c1\u7a2e\u5728\u5168\u7403\u5c64\u9762\u7684\u81e8\u5e8a\u958b\u767c\uff0c\u8b93\u66f4\u591a\u5b89\u5168\u6709\u6548\u7684\u85e5\u7269\u76e1\u5feb\u4e0a\u5e02\uff0c\u65e9\u65e5\u60e0\u53ca\u60a3\u8005\u3002\u300d \u6b64\u9805\u7814\u7a76\u57282024 ASH\u5e74\u6703\u4e0a\u5c55\u793a\u7684\u6838\u5fc3\u8981\u9ede\u5982\u4e0b\uff1a Safety and Efficacy of Olverembatinib (HQP1351) Combined with Lisaftoclax (APG-2575) in Children and Adolescents with Relapsed\\\/Refractory Philadelphia Chromosome\u2013Positive Acute Lymphoblastic Leukemia (R\\\/R Ph+ ALL): First Report from a Phase 1 Study\u5967\u96f7\u5df4\u66ff\u5c3c\uff08HQP1351\uff09\u806f\u5408Lisaftoclax\uff08APG-2575\uff09\u6cbb\u7642\u5fa9\u767c\\\/\u96e3\u6cbb\u6027\u8cbb\u57ce\u67d3\u8272\u9ad4\u967d\u6027\u6025\u6027\u6dcb\u5df4\u7d30\u80de\u767d\u8840\u75c5\uff08R\\\/R Ph+ ALL\uff09\u5152\u7ae5\u53ca\u9752\u5c11\u5e74\u60a3\u8005\u7684\u5b89\u5168\u6027\u548c\u7642\u6548\uff1a\u4e00\u9805I\u671f\u81e8\u5e8a\u7814\u7a76\u7684\u9996\u6b21\u5831\u544a\u5c55\u793a\u5f62\u5f0f\uff1a\u58c1\u5831\u5c55\u793a\u6458\u8981\u7de8\u865f\uff1a1443\u5206\u6703\u5834\uff1a613. \u6025\u6027\u6dcb\u5df4\u7d30\u80de\u767d\u8840\u75c5\uff1a\u540c\u7a2e\u79fb\u690d\u4ee5\u5916\u7684\u7642\u6cd5\uff1a\u58c1\u5831\u5c55\u793aI\u6838\u5fc3\u8981\u9ede\uff1a\u7814\u7a76\u80cc\u666f\uff1a\u5967\u96f7\u5df4\u66ff\u5c3c\u662f\u65b0\u578b\u4e09\u4ee3TKI\uff0c\u5177\u6709\u826f\u597d\u8010\u53d7\u6027\uff0c\u4e26\u5728\u5df2\u63a5\u53d7\u6df1\u5ea6\u6cbb\u7642\u7684CP-CML\u60a3\u8005\u4e2d\uff08\u7121\u8ad6\u662f\u5426\u6709T315I\u7a81\u8b8a\uff09\u8868\u73fe\u51fa\u5f37\u5927\u4e14\u6301\u4e45\u7684\u6297\u767d\u8840\u75c5\u6d3b\u6027\u3002Lisaftoclax\u662f\u4e00\u7a2e\u65b0\u578bBcl-2\u6291\u5236\u5291\uff0c\u5728\u591a\u7a2e\u8840\u6db2\u60e1\u6027\u816b\u7624\u4e2d\u986f\u793a\u51fa\u6297\u816b\u7624\u6548\u679c\u3002\u76ee\u524d\uff0cR\\\/R Ph+ ALL\u5152\u7ae5\u60a3\u8005\u5c1a\u7121\u6709\u6548\u6cbb\u7642\u9078\u64c7\u3002 \u7814\u7a76\u4ecb\u7d39\uff1a\u672c\u7814\u7a76\u65e8\u5728\u63a2\u7d22\u5967\u96f7\u5df4\u66ff\u5c3c\u55ae\u85e5\u6216\u806f\u5408Lisaftoclax\u5728R\\\/R Ph+ ALL\u5152\u7ae5\u60a3\u8005\u4e2d\u7684\u5b89\u5168\u6027\u3001\u6709\u6548\u6027\u53ca\u85e5\u4ee3\u52d5\u529b\u5b78\uff08PK\uff09\u7279\u5fb5\u3002 \u5165\u7d44\u60a3\u8005\u548c\u7814\u7a76\u65b9\u6cd5\uff1a \u9019\u662f\u4e00\u9805\u958b\u653e\u6a19\u7c64\u7684Ib\u671f\u7814\u7a76\uff0c\u5165\u7d44\u7684\u70ba\u5e74\u9f61\u5c0f\u65bc18\u6b72\u7684R\\\/R Ph+ ALL\u5152\u7ae5\u60a3\u8005\uff0c\u9019\u4e9b\u60a3\u8005\u5c0d\u81f3\u5c11\u4e00\u7a2eTKI\u8010\u85e5\u6216\u4e0d\u8010\u53d7\uff08\u5982\u679c\u60a3\u8005\u651c\u5e36T315I\u7a81\u8b8a\uff0c\u5247\u4e0d\u8003\u616e\u65e2\u5f80TKI\u4f7f\u7528\u60c5\u6cc1\uff09\u3002\u60a3\u8005\u9700\u5177\u5099\u8db3\u5920\u7684Karnofsky\\\/Lansky\u529f\u80fd\u72c0\u614b\u8a55\u5206\u548c\u5668\u5b98\u529f\u80fd\u3002\u60a3\u6709\u8207Ph+ ALL\u7121\u95dc\u7684\u75c7\u72c0\u6027\u4e2d\u6a1e\u795e\u7d93\u7cfb\u7d71\u75be\u75c5\u6216\u986f\u8457\u51fa\u8840\u7684\u60a3\u8005\u88ab\u6392\u9664\u5728\u5916\u3002 \u5967\u96f7\u5df4\u66ff\u5c3c\u4ee5\u6210\u4eba\u7b49\u6548\u5291\u91cf\uff08AED\uff0940 mg\u53e3\u670d\uff0c\u9694\u65e5\u4e00\u6b21\uff0c\u6301\u7e8c2\u5468\uff08\u7b2c1-14\u5929\uff09\u3002\u7136\u5f8c\u540c\u5291\u91cf\u7684\u5967\u96f7\u5df4\u66ff\u5c3c\u806f\u5408Lisaftoclax\uff0c\u5f8c\u8005\u7684\u6307\u5b9a\u5291\u91cf\u70ba200\\\/400\\\/600 mg\uff08AED\uff09\uff0c\u6bcf\u65e5\u4e00\u6b21\uff08QD\uff09\uff0c\u7b2c13-42\u5929\uff08\u7b2c13-15\u5929\u97003\u5929\u5291\u91cf\u905e\u589e\uff09\u3002\u5730\u585e\u7c73\u677e\u4ee56 mg\\\/m2\\\/\u5929\u7684\u5291\u91cf\u5f9e\u7b2c15-42\u5929\u6bcf\u65e5\u53e3\u670d\u4e00\u6b21\u3002\u4e3b\u8981\u7d42\u9ede\u5305\u62ec\u5967\u96f7\u5df4\u66ff\u5c3c\u55ae\u85e5\\\/\u806f\u5408APG-2575\u7684\u5b89\u5168\u6027\u8a55\u4f30\u3001\u7e3d\u53cd\u61c9\u7387\uff08ORR\uff09\u3001MRD\u9670\u6027\u7387\u3001\u4ee5\u53caPK\u7279\u5fb5\u3002 \u5f9e2022\u5e749\u6708\u81f32024\u5e746\u6708\uff0c\u5171\u5165\u7d44\u4e8610\u4f8b\u60a3\u8005\u3002\u4e2d\u4f4d\u5e74\u9f61\uff08\u7bc4\u570d\uff09\u70ba13.0\uff0811-15\uff09\u6b72\uff0c\u5176\u4e2d6\u4f8b\u70ba\u7537\u6027\u3002\u4e2d\u4f4d\u9ad4\u91cd\uff08\u7bc4\u570d\uff09\u70ba49.85\uff0835.9-86.0\uff09kg\u30029\u4f8b\uff0890.0%\uff09\u60a3\u5152\u8868\u9054p190\u8f49\u9304\u672c\uff1b1\u4f8b\uff0810.0%\uff09\u8868\u9054p210\u8f49\u9304\u672c\u3002\u57fa\u7dda\u6642\uff0c3\u4f8b\u60a3\u5152\u651c\u5e36BCR-ABL1\u7a81\u8b8a\uff0c\u5305\u62ec2\u4f8bT315I\u7a81\u8b8a\u548c1\u4f8bF317L\u7a81\u8b8a\u30021\u4f8b\u60a3\u5152\u56e0\u5728\u7b2c1\u7642\u7a0b\u7b2c1\u5929\uff08C1D1\uff09\u767c\u751f\u7672\u7647\u800c\u9000\u51fa\u8a66\u9a57\uff0c9\u4f8b\u60a3\u5152\u88ab\u7d0d\u51653+3\u5291\u91cf\u905e\u589e\u6a21\u578b\uff1a\u6bcf\u7d44\uff08A\u3001B\u548cC\u7d44\uff09\u54043\u4f8b\u60a3\u5152\uff0c\u5206\u5225\u63a5\u53d7200\u3001400\u548c600 mg\uff08AED\uff09\u6307\u5b9a\u5291\u91cf\u7684Lisaftoclax\u3002\u9019\u4e9b\u60a3\u5152\u5b8c\u6210\u4e8642\u5929\u7684\u6cbb\u7642\uff0c\u4e26\u63a5\u53d7\u4e86\u4e3b\u8981\u7d42\u9ede\u8a55\u4f30\u3002 \u7642\u6548\u6578\u64da\uff1a\u57286\u4f8b\u5f62\u614b\u5b78\u53cd\u61c9\u53ef\u8a55\u4f30\u7684\u60a3\u5152\u4e2d\uff0c\u5728\u5967\u96f7\u5df4\u66ff\u5c3c\u55ae\u85e5\u6cbb\u7642\u7d50\u675f\u6642\uff08EOM\uff09\uff0c2\u4f8b\u9054\u5230CR\u4f34\u4e0d\u5b8c\u5168\u8840\u7d30\u80de\u6062\u5fa9\uff08CRi\uff09\uff0c2\u4f8b\u9054\u5230\u90e8\u5206\u7de9\u89e3\uff08PR\uff09\uff0cORR\uff08CR+CRi\uff09\u70ba33.3%\uff1b\u5728\u5967\u96f7\u5df4\u66ff\u5c3c\u548cLisaftoclax\u806f\u5408\u6cbb\u7642\u7d50\u675f\u6642\uff08EOC\uff09\uff0c5\u4f8b\uff0883.3%\uff09\u9054\u5230CR\uff1b\u57287\u4f8b\u5206\u5b50\u5b78\u53ef\u8a55\u4f30\u7684\u60a3\u5152\u4e2d\uff0c\u67095\uff0871.4%\uff09\u4f8b\u9054\u5230\u4e86MRD\u9670\u6027\uff0c\u5176\u4e2d1\u4f8b\u5728EOM\u9054\u5230\uff0c4\u4f8b\u5728EOC\u9054\u5230\u3002 \u5b89\u5168\u6027\u6578\u64da\uff1a 10\u4f8b\u60a3\u5152\u4e2d\u67096\u4f8b\u7d93\u6b77\u4e86\u2265 3\u7d1a\u7684\u8840\u6db2\u5b78\u6cbb\u7642\u671f\u9593\u51fa\u73fe\u7684\u4e0d\u826f\u4e8b\u4ef6\uff0c\u5305\u62ec\u8ca7\u8840\uff083\\\/10\uff09\u3001\u4e2d\u6027\u7c92\u7d30\u80de\u6e1b\u5c11\uff087\\\/10\uff09\u548c\u8840\u5c0f\u677f\u6e1b\u5c11\uff083\\\/10\uff09\uff1b1\u4f8b\u60a3\u5152\u56e03\u7d1a\u4e19\u6c28\u9178\u6c28\u57fa\u8f49\u79fb\u9176\u5347\u9ad8\u800c\u505c\u6b62\u6cbb\u7642\uff0c\u53e61\u4f8b\u60a3\u5152\u5728\u7b2c1\u7642\u7a0b\u7b2c1\u5929\uff08C1D1\uff09\u767c\u751f\u7672\u7647\u4e26\u9000\u51fa\u8a66\u9a57\u3002 \u521d\u6b65PK\u5206\u6790\u986f\u793a\uff0c\u5967\u96f7\u5df4\u66ff\u5c3c\u548cLisaftoclax\u5728\u5152\u7ae5\u548c\u6210\u4eba\u4e2d\u5177\u6709\u76f8\u4f3c\u7684PK\u7279\u5fb5\u548c\u53ef\u6bd4\u7684\u85e5\u7269\u66b4\u9732\uff0c\u7d93\u904e\u591a\u6b21\u7d66\u85e5\u5f8c\u672a\u898b\u986f\u8457\u84c4\u7a4d\u3002\u4e14\u5967\u96f7\u5df4\u66ff\u5c3c\u548cLisaftoclax\u4e4b\u9593\u672a\u89c0\u5bdf\u5230\u85e5\u7269\u76f8\u4e92\u4f5c\u7528\u3002 \u7d50\u8ad6\uff1a\u521d\u6b65\u6578\u64da\u8868\u660e\uff0c\u5967\u96f7\u5df4\u66ff\u5c3c\u806f\u5408Lisaftoclax\u70baR\\\/R Ph+ ALL\u60a3\u5152\u63d0\u4f9b\u4e86\u4e00\u7a2e\u5b89\u5168\u4e14\u6709\u6548\u7684\u6cbb\u7642\u9078\u64c7\u3002\u8a72\u65b9\u6848\u5728\u7121\u9700\u5f37\u5316\u7642\u6216\u514d\u75ab\u6cbb\u7642\u7684\u60c5\u6cc1\u4e0b\uff0c\u5be6\u73fe\u4e8683.3%\u7684CR\u7387\u548c71.4%\u7684MRD\u8f49\u9670\u7387\u3002\u76ee\u524d\uff0c\u8a72\u7814\u7a76\u6b63\u8655\u65bc\u5291\u91cf\u64f4\u5c55\u968e\u6bb5\u3002 \u95dc\u65bc\u4e9e\u76db\u91ab\u85e5 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\u8a72\u9805\u81e8\u5e8a\u7814\u7a76\u7684\u4e3b\u8981\u7814\u7a76\u8005\u3001\u4e2d\u570b\u91ab\u5b78\u79d1\u5b78\u9662\u8840\u6db2\u75c5\u91ab\u9662\u7afa\u66c9\u51e1\u6559\u6388\u8868\u793a\uff1a\u300c\u8fd1\u5e74\u4f86\u6211\u570b\u5152\u7ae5\u8840\u6db2\u75c5\u6574\u9ad4\u8a3a\u6cbb\u6c34\u5e73\u5df2\u6709\u5927\u5e45\u63d0\u5347\uff0c\u4f46\u662f\u5728Ph+ ALL\u9818\u57df\uff0c\u56e0\u70ba\u5176\u75be\u75c5\u7684\u7279\u6b8a\u6027\uff0c\u6574\u9ad4\u9810\u5f8c\u4f9d\u7136\u8f03\u5dee\uff0cR\/R Ph+ ALL\u6cbb\u7642\u4ecd\u6709\u5f88\u5927\u7684\u63a2\u7d22\u7a7a\u9593\u3002\u73fe\u5728\u7b2c\u4e09\u4ee3BCR-ABL1\u6291\u5236\u5291\u5967\u96f7\u5df4\u66ff\u5c3c\u806f\u5408Bcl-2\u6291\u5236\u5291APG-2575\u7684\u7814\u7a76\u7684\u521d\u6b65\u6578\u64da\u63d0\u793a\uff0c\u5728\u7121\u9700\u5f37\u5316\u7642\u6216\u514d\u75ab\u6cbb\u7642\u7684\u60c5\u6cc1\u4e0b\uff0c\u60a3\u5152\u53ef\u4ee5\u7372\u5f97\u76f8\u7576\u4e0d\u932f\u7684\u5b8c\u5168\u7de9\u89e3\u7387\u548c\u6b98\u7559\u75be\u75c5\u8f49\u9670\u7387\uff0c\u4e14\u8010\u53d7\u6027\u826f\u597d\u3002\u6211\u5011\u671f\u5f85\u5728\u63a5\u4e0b\u4f86\u7684\u81e8\u5e8a\u7814\u7a76\u4e2d\u9032\u4e00\u6b65\u78ba\u5b9a\u5169\u85e5\u806f\u5408\u7684\u5408\u9069\u5291\u91cf\u548c\u65b9\u6848\u3002\u70baR\/R Ph+ ALL\u5152\u7ae5\u60a3\u8005\uff0c\u63a2\u7d22\u66f4\u591a\u5b89\u5168\u4e14\u6709\u6548\u7684\u6cbb\u7642\u9078\u64c7\u3002\u300d \u4e9e\u76db\u91ab\u85e5\u9996\u5e2d\u91ab\u5b78\u5b98\u7fdf\u4e00\u5e06\u535a\u58eb\u8868\u793a\uff1a\u300c\u9019\u662f\u516c\u53f8\u5169\u500b\u91cd\u78c5\u54c1\u7a2e\u8010\u7acb\u514b\u00ae\u548cAPG-2575\u7684\u9996\u6b21\u806f\u7528\u3002\u5728\u9019\u4e00\u6cbb\u7642\u65b9\u6848\u4e2d\uff0cPh+ ALL\u5152\u7ae5\u60a3\u8005\u5728\u7121\u5316\u7642\u7684\u60c5\u6cc1\u4e0b\u4ecd\u7372\u5f97\u5353\u8d8a\u7684\u7642\u6548\u548c\u5b89\u5168\u6027\uff0c\u8d77\u6548\u8fc5\u901f\uff0c\u7de9\u89e3\u7387\u9ad8\u4e14\u7de9\u89e3\u7a0b\u5ea6\u6df1\u3002\u9019\u610f\u5473\u8457\u8a72\u806f\u5408\u6cbb\u7642\u65b9\u6848\u6709\u671b\u6210\u70baPh+ ALL\u9032\u5165\u300e\u7121\u5316\u7642\u300f\u6642\u4ee3\u7684\u65b0\u7684\u6cbb\u7642\u9078\u64c7\u3002\u672a\u4f86\uff0c\u6211\u5011\u5c07\u7e7c\u7e8c\u5805\u5b88\u300e\u89e3\u6c7a\u4e2d\u570b\u4e43\u81f3\u5168\u7403\u60a3\u8005\u5c1a\u672a\u6eff\u8db3\u7684\u81e8\u5e8a\u9700\u6c42\u300f\u9019\u4e00\u4f7f\u547d\uff0c\u52a0\u901f\u63a8\u9032\u516c\u53f8\u91cd\u9ede\u54c1\u7a2e\u5728\u5168\u7403\u5c64\u9762\u7684\u81e8\u5e8a\u958b\u767c\uff0c\u8b93\u66f4\u591a\u5b89\u5168\u6709\u6548\u7684\u85e5\u7269\u76e1\u5feb\u4e0a\u5e02\uff0c\u65e9\u65e5\u60e0\u53ca\u60a3\u8005\u3002\u300d \u6b64\u9805\u7814\u7a76\u57282024 ASH\u5e74\u6703\u4e0a\u5c55\u793a\u7684\u6838\u5fc3\u8981\u9ede\u5982\u4e0b\uff1a Safety and Efficacy of Olverembatinib (HQP1351) Combined with Lisaftoclax (APG-2575) in Children and Adolescents with Relapsed\/Refractory Philadelphia Chromosome\u2013Positive Acute Lymphoblastic Leukemia (R\/R Ph+ ALL): First Report from a Phase 1 Study\u5967\u96f7\u5df4\u66ff\u5c3c\uff08HQP1351\uff09\u806f\u5408Lisaftoclax\uff08APG-2575\uff09\u6cbb\u7642\u5fa9\u767c\/\u96e3\u6cbb\u6027\u8cbb\u57ce\u67d3\u8272\u9ad4\u967d\u6027\u6025\u6027\u6dcb\u5df4\u7d30\u80de\u767d\u8840\u75c5\uff08R\/R Ph+ ALL\uff09\u5152\u7ae5\u53ca\u9752\u5c11\u5e74\u60a3\u8005\u7684\u5b89\u5168\u6027\u548c\u7642\u6548\uff1a\u4e00\u9805I\u671f\u81e8\u5e8a\u7814\u7a76\u7684\u9996\u6b21\u5831\u544a\u5c55\u793a\u5f62\u5f0f\uff1a\u58c1\u5831\u5c55\u793a\u6458\u8981\u7de8\u865f\uff1a1443\u5206\u6703\u5834\uff1a613. \u6025\u6027\u6dcb\u5df4\u7d30\u80de\u767d\u8840\u75c5\uff1a\u540c\u7a2e\u79fb\u690d\u4ee5\u5916\u7684\u7642\u6cd5\uff1a\u58c1\u5831\u5c55\u793aI\u6838\u5fc3\u8981\u9ede\uff1a\u7814\u7a76\u80cc\u666f\uff1a\u5967\u96f7\u5df4\u66ff\u5c3c\u662f\u65b0\u578b\u4e09\u4ee3TKI\uff0c\u5177\u6709\u826f\u597d\u8010\u53d7\u6027\uff0c\u4e26\u5728\u5df2\u63a5\u53d7\u6df1\u5ea6\u6cbb\u7642\u7684CP-CML\u60a3\u8005\u4e2d\uff08\u7121\u8ad6\u662f\u5426\u6709T315I\u7a81\u8b8a\uff09\u8868\u73fe\u51fa\u5f37\u5927\u4e14\u6301\u4e45\u7684\u6297\u767d\u8840\u75c5\u6d3b\u6027\u3002Lisaftoclax\u662f\u4e00\u7a2e\u65b0\u578bBcl-2\u6291\u5236\u5291\uff0c\u5728\u591a\u7a2e\u8840\u6db2\u60e1\u6027\u816b\u7624\u4e2d\u986f\u793a\u51fa\u6297\u816b\u7624\u6548\u679c\u3002\u76ee\u524d\uff0cR\/R Ph+ ALL\u5152\u7ae5\u60a3\u8005\u5c1a\u7121\u6709\u6548\u6cbb\u7642\u9078\u64c7\u3002 \u7814\u7a76\u4ecb\u7d39\uff1a\u672c\u7814\u7a76\u65e8\u5728\u63a2\u7d22\u5967\u96f7\u5df4\u66ff\u5c3c\u55ae\u85e5\u6216\u806f\u5408Lisaftoclax\u5728R\/R Ph+ ALL\u5152\u7ae5\u60a3\u8005\u4e2d\u7684\u5b89\u5168\u6027\u3001\u6709\u6548\u6027\u53ca\u85e5\u4ee3\u52d5\u529b\u5b78\uff08PK\uff09\u7279\u5fb5\u3002 \u5165\u7d44\u60a3\u8005\u548c\u7814\u7a76\u65b9\u6cd5\uff1a   \u9019\u662f\u4e00\u9805\u958b\u653e\u6a19\u7c64\u7684Ib\u671f\u7814\u7a76\uff0c\u5165\u7d44\u7684\u70ba\u5e74\u9f61\u5c0f\u65bc18\u6b72\u7684R\/R Ph+ ALL\u5152\u7ae5\u60a3\u8005\uff0c\u9019\u4e9b\u60a3\u8005\u5c0d\u81f3\u5c11\u4e00\u7a2eTKI\u8010\u85e5\u6216\u4e0d\u8010\u53d7\uff08\u5982\u679c\u60a3\u8005\u651c\u5e36T315I\u7a81\u8b8a\uff0c\u5247\u4e0d\u8003\u616e\u65e2\u5f80TKI\u4f7f\u7528\u60c5\u6cc1\uff09\u3002\u60a3\u8005\u9700\u5177\u5099\u8db3\u5920\u7684Karnofsky\/Lansky\u529f\u80fd\u72c0\u614b\u8a55\u5206\u548c\u5668\u5b98\u529f\u80fd\u3002\u60a3\u6709\u8207Ph+ ALL\u7121\u95dc\u7684\u75c7\u72c0\u6027\u4e2d\u6a1e\u795e\u7d93\u7cfb\u7d71\u75be\u75c5\u6216\u986f\u8457\u51fa\u8840\u7684\u60a3\u8005\u88ab\u6392\u9664\u5728\u5916\u3002  \u5967\u96f7\u5df4\u66ff\u5c3c\u4ee5\u6210\u4eba\u7b49\u6548\u5291\u91cf\uff08AED\uff0940 mg\u53e3\u670d\uff0c\u9694\u65e5\u4e00\u6b21\uff0c\u6301\u7e8c2\u5468\uff08\u7b2c1-14\u5929\uff09\u3002\u7136\u5f8c\u540c\u5291\u91cf\u7684\u5967\u96f7\u5df4\u66ff\u5c3c\u806f\u5408Lisaftoclax\uff0c\u5f8c\u8005\u7684\u6307\u5b9a\u5291\u91cf\u70ba200\/400\/600 mg\uff08AED\uff09\uff0c\u6bcf\u65e5\u4e00\u6b21\uff08QD\uff09\uff0c\u7b2c13-42\u5929\uff08\u7b2c13-15\u5929\u97003\u5929\u5291\u91cf\u905e\u589e\uff09\u3002\u5730\u585e\u7c73\u677e\u4ee56 mg\/m2\/\u5929\u7684\u5291\u91cf\u5f9e\u7b2c15-42\u5929\u6bcf\u65e5\u53e3\u670d\u4e00\u6b21\u3002\u4e3b\u8981\u7d42\u9ede\u5305\u62ec\u5967\u96f7\u5df4\u66ff\u5c3c\u55ae\u85e5\/\u806f\u5408APG-2575\u7684\u5b89\u5168\u6027\u8a55\u4f30\u3001\u7e3d\u53cd\u61c9\u7387\uff08ORR\uff09\u3001MRD\u9670\u6027\u7387\u3001\u4ee5\u53caPK\u7279\u5fb5\u3002  \u5f9e2022\u5e749\u6708\u81f32024\u5e746\u6708\uff0c\u5171\u5165\u7d44\u4e8610\u4f8b\u60a3\u8005\u3002\u4e2d\u4f4d\u5e74\u9f61\uff08\u7bc4\u570d\uff09\u70ba13.0\uff0811-15\uff09\u6b72\uff0c\u5176\u4e2d6\u4f8b\u70ba\u7537\u6027\u3002\u4e2d\u4f4d\u9ad4\u91cd\uff08\u7bc4\u570d\uff09\u70ba49.85\uff0835.9-86.0\uff09kg\u30029\u4f8b\uff0890.0%\uff09\u60a3\u5152\u8868\u9054p190\u8f49\u9304\u672c\uff1b1\u4f8b\uff0810.0%\uff09\u8868\u9054p210\u8f49\u9304\u672c\u3002\u57fa\u7dda\u6642\uff0c3\u4f8b\u60a3\u5152\u651c\u5e36BCR-ABL1\u7a81\u8b8a\uff0c\u5305\u62ec2\u4f8bT315I\u7a81\u8b8a\u548c1\u4f8bF317L\u7a81\u8b8a\u30021\u4f8b\u60a3\u5152\u56e0\u5728\u7b2c1\u7642\u7a0b\u7b2c1\u5929\uff08C1D1\uff09\u767c\u751f\u7672\u7647\u800c\u9000\u51fa\u8a66\u9a57\uff0c9\u4f8b\u60a3\u5152\u88ab\u7d0d\u51653+3\u5291\u91cf\u905e\u589e\u6a21\u578b\uff1a\u6bcf\u7d44\uff08A\u3001B\u548cC\u7d44\uff09\u54043\u4f8b\u60a3\u5152\uff0c\u5206\u5225\u63a5\u53d7200\u3001400\u548c600 mg\uff08AED\uff09\u6307\u5b9a\u5291\u91cf\u7684Lisaftoclax\u3002\u9019\u4e9b\u60a3\u5152\u5b8c\u6210\u4e8642\u5929\u7684\u6cbb\u7642\uff0c\u4e26\u63a5\u53d7\u4e86\u4e3b\u8981\u7d42\u9ede\u8a55\u4f30\u3002  \u7642\u6548\u6578\u64da\uff1a\u57286\u4f8b\u5f62\u614b\u5b78\u53cd\u61c9\u53ef\u8a55\u4f30\u7684\u60a3\u5152\u4e2d\uff0c\u5728\u5967\u96f7\u5df4\u66ff\u5c3c\u55ae\u85e5\u6cbb\u7642\u7d50\u675f\u6642\uff08EOM\uff09\uff0c2\u4f8b\u9054\u5230CR\u4f34\u4e0d\u5b8c\u5168\u8840\u7d30\u80de\u6062\u5fa9\uff08CRi\uff09\uff0c2\u4f8b\u9054\u5230\u90e8\u5206\u7de9\u89e3\uff08PR\uff09\uff0cORR\uff08CR+CRi\uff09\u70ba33.3%\uff1b\u5728\u5967\u96f7\u5df4\u66ff\u5c3c\u548cLisaftoclax\u806f\u5408\u6cbb\u7642\u7d50\u675f\u6642\uff08EOC\uff09\uff0c5\u4f8b\uff0883.3%\uff09\u9054\u5230CR\uff1b\u57287\u4f8b\u5206\u5b50\u5b78\u53ef\u8a55\u4f30\u7684\u60a3\u5152\u4e2d\uff0c\u67095\uff0871.4%\uff09\u4f8b\u9054\u5230\u4e86MRD\u9670\u6027\uff0c\u5176\u4e2d1\u4f8b\u5728EOM\u9054\u5230\uff0c4\u4f8b\u5728EOC\u9054\u5230\u3002 \u5b89\u5168\u6027\u6578\u64da\uff1a   10\u4f8b\u60a3\u5152\u4e2d\u67096\u4f8b\u7d93\u6b77\u4e86\u2265 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ALL\u6cbb\u7642\u4ecd\u6709\u5f88\u5927\u7684\u63a2\u7d22\u7a7a\u9593\u3002\u73fe\u5728\u7b2c\u4e09\u4ee3BCR-ABL1\u6291\u5236\u5291\u5967\u96f7\u5df4\u66ff\u5c3c\u806f\u5408Bcl-2\u6291\u5236\u5291APG-2575\u7684\u7814\u7a76\u7684\u521d\u6b65\u6578\u64da\u63d0\u793a\uff0c\u5728\u7121\u9700\u5f37\u5316\u7642\u6216\u514d\u75ab\u6cbb\u7642\u7684\u60c5\u6cc1\u4e0b\uff0c\u60a3\u5152\u53ef\u4ee5\u7372\u5f97\u76f8\u7576\u4e0d\u932f\u7684\u5b8c\u5168\u7de9\u89e3\u7387\u548c\u6b98\u7559\u75be\u75c5\u8f49\u9670\u7387\uff0c\u4e14\u8010\u53d7\u6027\u826f\u597d\u3002\u6211\u5011\u671f\u5f85\u5728\u63a5\u4e0b\u4f86\u7684\u81e8\u5e8a\u7814\u7a76\u4e2d\u9032\u4e00\u6b65\u78ba\u5b9a\u5169\u85e5\u806f\u5408\u7684\u5408\u9069\u5291\u91cf\u548c\u65b9\u6848\u3002\u70baR\/R Ph+ ALL\u5152\u7ae5\u60a3\u8005\uff0c\u63a2\u7d22\u66f4\u591a\u5b89\u5168\u4e14\u6709\u6548\u7684\u6cbb\u7642\u9078\u64c7\u3002\u300d \u4e9e\u76db\u91ab\u85e5\u9996\u5e2d\u91ab\u5b78\u5b98\u7fdf\u4e00\u5e06\u535a\u58eb\u8868\u793a\uff1a\u300c\u9019\u662f\u516c\u53f8\u5169\u500b\u91cd\u78c5\u54c1\u7a2e\u8010\u7acb\u514b\u00ae\u548cAPG-2575\u7684\u9996\u6b21\u806f\u7528\u3002\u5728\u9019\u4e00\u6cbb\u7642\u65b9\u6848\u4e2d\uff0cPh+ ALL\u5152\u7ae5\u60a3\u8005\u5728\u7121\u5316\u7642\u7684\u60c5\u6cc1\u4e0b\u4ecd\u7372\u5f97\u5353\u8d8a\u7684\u7642\u6548\u548c\u5b89\u5168\u6027\uff0c\u8d77\u6548\u8fc5\u901f\uff0c\u7de9\u89e3\u7387\u9ad8\u4e14\u7de9\u89e3\u7a0b\u5ea6\u6df1\u3002\u9019\u610f\u5473\u8457\u8a72\u806f\u5408\u6cbb\u7642\u65b9\u6848\u6709\u671b\u6210\u70baPh+ ALL\u9032\u5165\u300e\u7121\u5316\u7642\u300f\u6642\u4ee3\u7684\u65b0\u7684\u6cbb\u7642\u9078\u64c7\u3002\u672a\u4f86\uff0c\u6211\u5011\u5c07\u7e7c\u7e8c\u5805\u5b88\u300e\u89e3\u6c7a\u4e2d\u570b\u4e43\u81f3\u5168\u7403\u60a3\u8005\u5c1a\u672a\u6eff\u8db3\u7684\u81e8\u5e8a\u9700\u6c42\u300f\u9019\u4e00\u4f7f\u547d\uff0c\u52a0\u901f\u63a8\u9032\u516c\u53f8\u91cd\u9ede\u54c1\u7a2e\u5728\u5168\u7403\u5c64\u9762\u7684\u81e8\u5e8a\u958b\u767c\uff0c\u8b93\u66f4\u591a\u5b89\u5168\u6709\u6548\u7684\u85e5\u7269\u76e1\u5feb\u4e0a\u5e02\uff0c\u65e9\u65e5\u60e0\u53ca\u60a3\u8005\u3002\u300d \u6b64\u9805\u7814\u7a76\u57282024 ASH\u5e74\u6703\u4e0a\u5c55\u793a\u7684\u6838\u5fc3\u8981\u9ede\u5982\u4e0b\uff1a Safety and Efficacy of Olverembatinib (HQP1351) Combined with Lisaftoclax (APG-2575) in Children and Adolescents with Relapsed\/Refractory Philadelphia Chromosome\u2013Positive Acute Lymphoblastic Leukemia (R\/R Ph+ ALL): First Report from a Phase 1 Study\u5967\u96f7\u5df4\u66ff\u5c3c\uff08HQP1351\uff09\u806f\u5408Lisaftoclax\uff08APG-2575\uff09\u6cbb\u7642\u5fa9\u767c\/\u96e3\u6cbb\u6027\u8cbb\u57ce\u67d3\u8272\u9ad4\u967d\u6027\u6025\u6027\u6dcb\u5df4\u7d30\u80de\u767d\u8840\u75c5\uff08R\/R Ph+ ALL\uff09\u5152\u7ae5\u53ca\u9752\u5c11\u5e74\u60a3\u8005\u7684\u5b89\u5168\u6027\u548c\u7642\u6548\uff1a\u4e00\u9805I\u671f\u81e8\u5e8a\u7814\u7a76\u7684\u9996\u6b21\u5831\u544a\u5c55\u793a\u5f62\u5f0f\uff1a\u58c1\u5831\u5c55\u793a\u6458\u8981\u7de8\u865f\uff1a1443\u5206\u6703\u5834\uff1a613. \u6025\u6027\u6dcb\u5df4\u7d30\u80de\u767d\u8840\u75c5\uff1a\u540c\u7a2e\u79fb\u690d\u4ee5\u5916\u7684\u7642\u6cd5\uff1a\u58c1\u5831\u5c55\u793aI\u6838\u5fc3\u8981\u9ede\uff1a\u7814\u7a76\u80cc\u666f\uff1a\u5967\u96f7\u5df4\u66ff\u5c3c\u662f\u65b0\u578b\u4e09\u4ee3TKI\uff0c\u5177\u6709\u826f\u597d\u8010\u53d7\u6027\uff0c\u4e26\u5728\u5df2\u63a5\u53d7\u6df1\u5ea6\u6cbb\u7642\u7684CP-CML\u60a3\u8005\u4e2d\uff08\u7121\u8ad6\u662f\u5426\u6709T315I\u7a81\u8b8a\uff09\u8868\u73fe\u51fa\u5f37\u5927\u4e14\u6301\u4e45\u7684\u6297\u767d\u8840\u75c5\u6d3b\u6027\u3002Lisaftoclax\u662f\u4e00\u7a2e\u65b0\u578bBcl-2\u6291\u5236\u5291\uff0c\u5728\u591a\u7a2e\u8840\u6db2\u60e1\u6027\u816b\u7624\u4e2d\u986f\u793a\u51fa\u6297\u816b\u7624\u6548\u679c\u3002\u76ee\u524d\uff0cR\/R Ph+ ALL\u5152\u7ae5\u60a3\u8005\u5c1a\u7121\u6709\u6548\u6cbb\u7642\u9078\u64c7\u3002 \u7814\u7a76\u4ecb\u7d39\uff1a\u672c\u7814\u7a76\u65e8\u5728\u63a2\u7d22\u5967\u96f7\u5df4\u66ff\u5c3c\u55ae\u85e5\u6216\u806f\u5408Lisaftoclax\u5728R\/R Ph+ ALL\u5152\u7ae5\u60a3\u8005\u4e2d\u7684\u5b89\u5168\u6027\u3001\u6709\u6548\u6027\u53ca\u85e5\u4ee3\u52d5\u529b\u5b78\uff08PK\uff09\u7279\u5fb5\u3002 \u5165\u7d44\u60a3\u8005\u548c\u7814\u7a76\u65b9\u6cd5\uff1a   \u9019\u662f\u4e00\u9805\u958b\u653e\u6a19\u7c64\u7684Ib\u671f\u7814\u7a76\uff0c\u5165\u7d44\u7684\u70ba\u5e74\u9f61\u5c0f\u65bc18\u6b72\u7684R\/R Ph+ ALL\u5152\u7ae5\u60a3\u8005\uff0c\u9019\u4e9b\u60a3\u8005\u5c0d\u81f3\u5c11\u4e00\u7a2eTKI\u8010\u85e5\u6216\u4e0d\u8010\u53d7\uff08\u5982\u679c\u60a3\u8005\u651c\u5e36T315I\u7a81\u8b8a\uff0c\u5247\u4e0d\u8003\u616e\u65e2\u5f80TKI\u4f7f\u7528\u60c5\u6cc1\uff09\u3002\u60a3\u8005\u9700\u5177\u5099\u8db3\u5920\u7684Karnofsky\/Lansky\u529f\u80fd\u72c0\u614b\u8a55\u5206\u548c\u5668\u5b98\u529f\u80fd\u3002\u60a3\u6709\u8207Ph+ ALL\u7121\u95dc\u7684\u75c7\u72c0\u6027\u4e2d\u6a1e\u795e\u7d93\u7cfb\u7d71\u75be\u75c5\u6216\u986f\u8457\u51fa\u8840\u7684\u60a3\u8005\u88ab\u6392\u9664\u5728\u5916\u3002  \u5967\u96f7\u5df4\u66ff\u5c3c\u4ee5\u6210\u4eba\u7b49\u6548\u5291\u91cf\uff08AED\uff0940 mg\u53e3\u670d\uff0c\u9694\u65e5\u4e00\u6b21\uff0c\u6301\u7e8c2\u5468\uff08\u7b2c1-14\u5929\uff09\u3002\u7136\u5f8c\u540c\u5291\u91cf\u7684\u5967\u96f7\u5df4\u66ff\u5c3c\u806f\u5408Lisaftoclax\uff0c\u5f8c\u8005\u7684\u6307\u5b9a\u5291\u91cf\u70ba200\/400\/600 mg\uff08AED\uff09\uff0c\u6bcf\u65e5\u4e00\u6b21\uff08QD\uff09\uff0c\u7b2c13-42\u5929\uff08\u7b2c13-15\u5929\u97003\u5929\u5291\u91cf\u905e\u589e\uff09\u3002\u5730\u585e\u7c73\u677e\u4ee56 mg\/m2\/\u5929\u7684\u5291\u91cf\u5f9e\u7b2c15-42\u5929\u6bcf\u65e5\u53e3\u670d\u4e00\u6b21\u3002\u4e3b\u8981\u7d42\u9ede\u5305\u62ec\u5967\u96f7\u5df4\u66ff\u5c3c\u55ae\u85e5\/\u806f\u5408APG-2575\u7684\u5b89\u5168\u6027\u8a55\u4f30\u3001\u7e3d\u53cd\u61c9\u7387\uff08ORR\uff09\u3001MRD\u9670\u6027\u7387\u3001\u4ee5\u53caPK\u7279\u5fb5\u3002  \u5f9e2022\u5e749\u6708\u81f32024\u5e746\u6708\uff0c\u5171\u5165\u7d44\u4e8610\u4f8b\u60a3\u8005\u3002\u4e2d\u4f4d\u5e74\u9f61\uff08\u7bc4\u570d\uff09\u70ba13.0\uff0811-15\uff09\u6b72\uff0c\u5176\u4e2d6\u4f8b\u70ba\u7537\u6027\u3002\u4e2d\u4f4d\u9ad4\u91cd\uff08\u7bc4\u570d\uff09\u70ba49.85\uff0835.9-86.0\uff09kg\u30029\u4f8b\uff0890.0%\uff09\u60a3\u5152\u8868\u9054p190\u8f49\u9304\u672c\uff1b1\u4f8b\uff0810.0%\uff09\u8868\u9054p210\u8f49\u9304\u672c\u3002\u57fa\u7dda\u6642\uff0c3\u4f8b\u60a3\u5152\u651c\u5e36BCR-ABL1\u7a81\u8b8a\uff0c\u5305\u62ec2\u4f8bT315I\u7a81\u8b8a\u548c1\u4f8bF317L\u7a81\u8b8a\u30021\u4f8b\u60a3\u5152\u56e0\u5728\u7b2c1\u7642\u7a0b\u7b2c1\u5929\uff08C1D1\uff09\u767c\u751f\u7672\u7647\u800c\u9000\u51fa\u8a66\u9a57\uff0c9\u4f8b\u60a3\u5152\u88ab\u7d0d\u51653+3\u5291\u91cf\u905e\u589e\u6a21\u578b\uff1a\u6bcf\u7d44\uff08A\u3001B\u548cC\u7d44\uff09\u54043\u4f8b\u60a3\u5152\uff0c\u5206\u5225\u63a5\u53d7200\u3001400\u548c600 mg\uff08AED\uff09\u6307\u5b9a\u5291\u91cf\u7684Lisaftoclax\u3002\u9019\u4e9b\u60a3\u5152\u5b8c\u6210\u4e8642\u5929\u7684\u6cbb\u7642\uff0c\u4e26\u63a5\u53d7\u4e86\u4e3b\u8981\u7d42\u9ede\u8a55\u4f30\u3002  \u7642\u6548\u6578\u64da\uff1a\u57286\u4f8b\u5f62\u614b\u5b78\u53cd\u61c9\u53ef\u8a55\u4f30\u7684\u60a3\u5152\u4e2d\uff0c\u5728\u5967\u96f7\u5df4\u66ff\u5c3c\u55ae\u85e5\u6cbb\u7642\u7d50\u675f\u6642\uff08EOM\uff09\uff0c2\u4f8b\u9054\u5230CR\u4f34\u4e0d\u5b8c\u5168\u8840\u7d30\u80de\u6062\u5fa9\uff08CRi\uff09\uff0c2\u4f8b\u9054\u5230\u90e8\u5206\u7de9\u89e3\uff08PR\uff09\uff0cORR\uff08CR+CRi\uff09\u70ba33.3%\uff1b\u5728\u5967\u96f7\u5df4\u66ff\u5c3c\u548cLisaftoclax\u806f\u5408\u6cbb\u7642\u7d50\u675f\u6642\uff08EOC\uff09\uff0c5\u4f8b\uff0883.3%\uff09\u9054\u5230CR\uff1b\u57287\u4f8b\u5206\u5b50\u5b78\u53ef\u8a55\u4f30\u7684\u60a3\u5152\u4e2d\uff0c\u67095\uff0871.4%\uff09\u4f8b\u9054\u5230\u4e86MRD\u9670\u6027\uff0c\u5176\u4e2d1\u4f8b\u5728EOM\u9054\u5230\uff0c4\u4f8b\u5728EOC\u9054\u5230\u3002 \u5b89\u5168\u6027\u6578\u64da\uff1a   10\u4f8b\u60a3\u5152\u4e2d\u67096\u4f8b\u7d93\u6b77\u4e86\u2265 3\u7d1a\u7684\u8840\u6db2\u5b78\u6cbb\u7642\u671f\u9593\u51fa\u73fe\u7684\u4e0d\u826f\u4e8b\u4ef6\uff0c\u5305\u62ec\u8ca7\u8840\uff083\/10\uff09\u3001\u4e2d\u6027\u7c92\u7d30\u80de\u6e1b\u5c11\uff087\/10\uff09\u548c\u8840\u5c0f\u677f\u6e1b\u5c11\uff083\/10\uff09\uff1b1\u4f8b\u60a3\u5152\u56e03\u7d1a\u4e19\u6c28\u9178\u6c28\u57fa\u8f49\u79fb\u9176\u5347\u9ad8\u800c\u505c\u6b62\u6cbb\u7642\uff0c\u53e61\u4f8b\u60a3\u5152\u5728\u7b2c1\u7642\u7a0b\u7b2c1\u5929\uff08C1D1\uff09\u767c\u751f\u7672\u7647\u4e26\u9000\u51fa\u8a66\u9a57\u3002  \u521d\u6b65PK\u5206\u6790\u986f\u793a\uff0c\u5967\u96f7\u5df4\u66ff\u5c3c\u548cLisaftoclax\u5728\u5152\u7ae5\u548c\u6210\u4eba\u4e2d\u5177\u6709\u76f8\u4f3c\u7684PK\u7279\u5fb5\u548c\u53ef\u6bd4\u7684\u85e5\u7269\u66b4\u9732\uff0c\u7d93\u904e\u591a\u6b21\u7d66\u85e5\u5f8c\u672a\u898b\u986f\u8457\u84c4\u7a4d\u3002\u4e14\u5967\u96f7\u5df4\u66ff\u5c3c\u548cLisaftoclax\u4e4b\u9593\u672a\u89c0\u5bdf\u5230\u85e5\u7269\u76f8\u4e92\u4f5c\u7528\u3002  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\u8a72\u9805\u81e8\u5e8a\u7814\u7a76\u7684\u4e3b\u8981\u7814\u7a76\u8005\u3001\u4e2d\u570b\u91ab\u5b78\u79d1\u5b78\u9662\u8840\u6db2\u75c5\u91ab\u9662\u7afa\u66c9\u51e1\u6559\u6388\u8868\u793a\uff1a\u300c\u8fd1\u5e74\u4f86\u6211\u570b\u5152\u7ae5\u8840\u6db2\u75c5\u6574\u9ad4\u8a3a\u6cbb\u6c34\u5e73\u5df2\u6709\u5927\u5e45\u63d0\u5347\uff0c\u4f46\u662f\u5728Ph+ ALL\u9818\u57df\uff0c\u56e0\u70ba\u5176\u75be\u75c5\u7684\u7279\u6b8a\u6027\uff0c\u6574\u9ad4\u9810\u5f8c\u4f9d\u7136\u8f03\u5dee\uff0cR\/R Ph+ ALL\u6cbb\u7642\u4ecd\u6709\u5f88\u5927\u7684\u63a2\u7d22\u7a7a\u9593\u3002\u73fe\u5728\u7b2c\u4e09\u4ee3BCR-ABL1\u6291\u5236\u5291\u5967\u96f7\u5df4\u66ff\u5c3c\u806f\u5408Bcl-2\u6291\u5236\u5291APG-2575\u7684\u7814\u7a76\u7684\u521d\u6b65\u6578\u64da\u63d0\u793a\uff0c\u5728\u7121\u9700\u5f37\u5316\u7642\u6216\u514d\u75ab\u6cbb\u7642\u7684\u60c5\u6cc1\u4e0b\uff0c\u60a3\u5152\u53ef\u4ee5\u7372\u5f97\u76f8\u7576\u4e0d\u932f\u7684\u5b8c\u5168\u7de9\u89e3\u7387\u548c\u6b98\u7559\u75be\u75c5\u8f49\u9670\u7387\uff0c\u4e14\u8010\u53d7\u6027\u826f\u597d\u3002\u6211\u5011\u671f\u5f85\u5728\u63a5\u4e0b\u4f86\u7684\u81e8\u5e8a\u7814\u7a76\u4e2d\u9032\u4e00\u6b65\u78ba\u5b9a\u5169\u85e5\u806f\u5408\u7684\u5408\u9069\u5291\u91cf\u548c\u65b9\u6848\u3002\u70baR\/R Ph+ ALL\u5152\u7ae5\u60a3\u8005\uff0c\u63a2\u7d22\u66f4\u591a\u5b89\u5168\u4e14\u6709\u6548\u7684\u6cbb\u7642\u9078\u64c7\u3002\u300d \u4e9e\u76db\u91ab\u85e5\u9996\u5e2d\u91ab\u5b78\u5b98\u7fdf\u4e00\u5e06\u535a\u58eb\u8868\u793a\uff1a\u300c\u9019\u662f\u516c\u53f8\u5169\u500b\u91cd\u78c5\u54c1\u7a2e\u8010\u7acb\u514b\u00ae\u548cAPG-2575\u7684\u9996\u6b21\u806f\u7528\u3002\u5728\u9019\u4e00\u6cbb\u7642\u65b9\u6848\u4e2d\uff0cPh+ ALL\u5152\u7ae5\u60a3\u8005\u5728\u7121\u5316\u7642\u7684\u60c5\u6cc1\u4e0b\u4ecd\u7372\u5f97\u5353\u8d8a\u7684\u7642\u6548\u548c\u5b89\u5168\u6027\uff0c\u8d77\u6548\u8fc5\u901f\uff0c\u7de9\u89e3\u7387\u9ad8\u4e14\u7de9\u89e3\u7a0b\u5ea6\u6df1\u3002\u9019\u610f\u5473\u8457\u8a72\u806f\u5408\u6cbb\u7642\u65b9\u6848\u6709\u671b\u6210\u70baPh+ ALL\u9032\u5165\u300e\u7121\u5316\u7642\u300f\u6642\u4ee3\u7684\u65b0\u7684\u6cbb\u7642\u9078\u64c7\u3002\u672a\u4f86\uff0c\u6211\u5011\u5c07\u7e7c\u7e8c\u5805\u5b88\u300e\u89e3\u6c7a\u4e2d\u570b\u4e43\u81f3\u5168\u7403\u60a3\u8005\u5c1a\u672a\u6eff\u8db3\u7684\u81e8\u5e8a\u9700\u6c42\u300f\u9019\u4e00\u4f7f\u547d\uff0c\u52a0\u901f\u63a8\u9032\u516c\u53f8\u91cd\u9ede\u54c1\u7a2e\u5728\u5168\u7403\u5c64\u9762\u7684\u81e8\u5e8a\u958b\u767c\uff0c\u8b93\u66f4\u591a\u5b89\u5168\u6709\u6548\u7684\u85e5\u7269\u76e1\u5feb\u4e0a\u5e02\uff0c\u65e9\u65e5\u60e0\u53ca\u60a3\u8005\u3002\u300d \u6b64\u9805\u7814\u7a76\u57282024 ASH\u5e74\u6703\u4e0a\u5c55\u793a\u7684\u6838\u5fc3\u8981\u9ede\u5982\u4e0b\uff1a Safety and Efficacy of Olverembatinib (HQP1351) Combined with Lisaftoclax (APG-2575) in Children and Adolescents with Relapsed\/Refractory Philadelphia Chromosome\u2013Positive Acute Lymphoblastic Leukemia (R\/R Ph+ ALL): First Report from a Phase 1 Study\u5967\u96f7\u5df4\u66ff\u5c3c\uff08HQP1351\uff09\u806f\u5408Lisaftoclax\uff08APG-2575\uff09\u6cbb\u7642\u5fa9\u767c\/\u96e3\u6cbb\u6027\u8cbb\u57ce\u67d3\u8272\u9ad4\u967d\u6027\u6025\u6027\u6dcb\u5df4\u7d30\u80de\u767d\u8840\u75c5\uff08R\/R Ph+ ALL\uff09\u5152\u7ae5\u53ca\u9752\u5c11\u5e74\u60a3\u8005\u7684\u5b89\u5168\u6027\u548c\u7642\u6548\uff1a\u4e00\u9805I\u671f\u81e8\u5e8a\u7814\u7a76\u7684\u9996\u6b21\u5831\u544a\u5c55\u793a\u5f62\u5f0f\uff1a\u58c1\u5831\u5c55\u793a\u6458\u8981\u7de8\u865f\uff1a1443\u5206\u6703\u5834\uff1a613. \u6025\u6027\u6dcb\u5df4\u7d30\u80de\u767d\u8840\u75c5\uff1a\u540c\u7a2e\u79fb\u690d\u4ee5\u5916\u7684\u7642\u6cd5\uff1a\u58c1\u5831\u5c55\u793aI\u6838\u5fc3\u8981\u9ede\uff1a\u7814\u7a76\u80cc\u666f\uff1a\u5967\u96f7\u5df4\u66ff\u5c3c\u662f\u65b0\u578b\u4e09\u4ee3TKI\uff0c\u5177\u6709\u826f\u597d\u8010\u53d7\u6027\uff0c\u4e26\u5728\u5df2\u63a5\u53d7\u6df1\u5ea6\u6cbb\u7642\u7684CP-CML\u60a3\u8005\u4e2d\uff08\u7121\u8ad6\u662f\u5426\u6709T315I\u7a81\u8b8a\uff09\u8868\u73fe\u51fa\u5f37\u5927\u4e14\u6301\u4e45\u7684\u6297\u767d\u8840\u75c5\u6d3b\u6027\u3002Lisaftoclax\u662f\u4e00\u7a2e\u65b0\u578bBcl-2\u6291\u5236\u5291\uff0c\u5728\u591a\u7a2e\u8840\u6db2\u60e1\u6027\u816b\u7624\u4e2d\u986f\u793a\u51fa\u6297\u816b\u7624\u6548\u679c\u3002\u76ee\u524d\uff0cR\/R Ph+ ALL\u5152\u7ae5\u60a3\u8005\u5c1a\u7121\u6709\u6548\u6cbb\u7642\u9078\u64c7\u3002 \u7814\u7a76\u4ecb\u7d39\uff1a\u672c\u7814\u7a76\u65e8\u5728\u63a2\u7d22\u5967\u96f7\u5df4\u66ff\u5c3c\u55ae\u85e5\u6216\u806f\u5408Lisaftoclax\u5728R\/R Ph+ ALL\u5152\u7ae5\u60a3\u8005\u4e2d\u7684\u5b89\u5168\u6027\u3001\u6709\u6548\u6027\u53ca\u85e5\u4ee3\u52d5\u529b\u5b78\uff08PK\uff09\u7279\u5fb5\u3002 \u5165\u7d44\u60a3\u8005\u548c\u7814\u7a76\u65b9\u6cd5\uff1a \u9019\u662f\u4e00\u9805\u958b\u653e\u6a19\u7c64\u7684Ib\u671f\u7814\u7a76\uff0c\u5165\u7d44\u7684\u70ba\u5e74\u9f61\u5c0f\u65bc18\u6b72\u7684R\/R Ph+ ALL\u5152\u7ae5\u60a3\u8005\uff0c\u9019\u4e9b\u60a3\u8005\u5c0d\u81f3\u5c11\u4e00\u7a2eTKI\u8010\u85e5\u6216\u4e0d\u8010\u53d7\uff08\u5982\u679c\u60a3\u8005\u651c\u5e36T315I\u7a81\u8b8a\uff0c\u5247\u4e0d\u8003\u616e\u65e2\u5f80TKI\u4f7f\u7528\u60c5\u6cc1\uff09\u3002\u60a3\u8005\u9700\u5177\u5099\u8db3\u5920\u7684Karnofsky\/Lansky\u529f\u80fd\u72c0\u614b\u8a55\u5206\u548c\u5668\u5b98\u529f\u80fd\u3002\u60a3\u6709\u8207Ph+ ALL\u7121\u95dc\u7684\u75c7\u72c0\u6027\u4e2d\u6a1e\u795e\u7d93\u7cfb\u7d71\u75be\u75c5\u6216\u986f\u8457\u51fa\u8840\u7684\u60a3\u8005\u88ab\u6392\u9664\u5728\u5916\u3002 \u5967\u96f7\u5df4\u66ff\u5c3c\u4ee5\u6210\u4eba\u7b49\u6548\u5291\u91cf\uff08AED\uff0940 mg\u53e3\u670d\uff0c\u9694\u65e5\u4e00\u6b21\uff0c\u6301\u7e8c2\u5468\uff08\u7b2c1-14\u5929\uff09\u3002\u7136\u5f8c\u540c\u5291\u91cf\u7684\u5967\u96f7\u5df4\u66ff\u5c3c\u806f\u5408Lisaftoclax\uff0c\u5f8c\u8005\u7684\u6307\u5b9a\u5291\u91cf\u70ba200\/400\/600 mg\uff08AED\uff09\uff0c\u6bcf\u65e5\u4e00\u6b21\uff08QD\uff09\uff0c\u7b2c13-42\u5929\uff08\u7b2c13-15\u5929\u97003\u5929\u5291\u91cf\u905e\u589e\uff09\u3002\u5730\u585e\u7c73\u677e\u4ee56 mg\/m2\/\u5929\u7684\u5291\u91cf\u5f9e\u7b2c15-42\u5929\u6bcf\u65e5\u53e3\u670d\u4e00\u6b21\u3002\u4e3b\u8981\u7d42\u9ede\u5305\u62ec\u5967\u96f7\u5df4\u66ff\u5c3c\u55ae\u85e5\/\u806f\u5408APG-2575\u7684\u5b89\u5168\u6027\u8a55\u4f30\u3001\u7e3d\u53cd\u61c9\u7387\uff08ORR\uff09\u3001MRD\u9670\u6027\u7387\u3001\u4ee5\u53caPK\u7279\u5fb5\u3002 \u5f9e2022\u5e749\u6708\u81f32024\u5e746\u6708\uff0c\u5171\u5165\u7d44\u4e8610\u4f8b\u60a3\u8005\u3002\u4e2d\u4f4d\u5e74\u9f61\uff08\u7bc4\u570d\uff09\u70ba13.0\uff0811-15\uff09\u6b72\uff0c\u5176\u4e2d6\u4f8b\u70ba\u7537\u6027\u3002\u4e2d\u4f4d\u9ad4\u91cd\uff08\u7bc4\u570d\uff09\u70ba49.85\uff0835.9-86.0\uff09kg\u30029\u4f8b\uff0890.0%\uff09\u60a3\u5152\u8868\u9054p190\u8f49\u9304\u672c\uff1b1\u4f8b\uff0810.0%\uff09\u8868\u9054p210\u8f49\u9304\u672c\u3002\u57fa\u7dda\u6642\uff0c3\u4f8b\u60a3\u5152\u651c\u5e36BCR-ABL1\u7a81\u8b8a\uff0c\u5305\u62ec2\u4f8bT315I\u7a81\u8b8a\u548c1\u4f8bF317L\u7a81\u8b8a\u30021\u4f8b\u60a3\u5152\u56e0\u5728\u7b2c1\u7642\u7a0b\u7b2c1\u5929\uff08C1D1\uff09\u767c\u751f\u7672\u7647\u800c\u9000\u51fa\u8a66\u9a57\uff0c9\u4f8b\u60a3\u5152\u88ab\u7d0d\u51653+3\u5291\u91cf\u905e\u589e\u6a21\u578b\uff1a\u6bcf\u7d44\uff08A\u3001B\u548cC\u7d44\uff09\u54043\u4f8b\u60a3\u5152\uff0c\u5206\u5225\u63a5\u53d7200\u3001400\u548c600 mg\uff08AED\uff09\u6307\u5b9a\u5291\u91cf\u7684Lisaftoclax\u3002\u9019\u4e9b\u60a3\u5152\u5b8c\u6210\u4e8642\u5929\u7684\u6cbb\u7642\uff0c\u4e26\u63a5\u53d7\u4e86\u4e3b\u8981\u7d42\u9ede\u8a55\u4f30\u3002 \u7642\u6548\u6578\u64da\uff1a\u57286\u4f8b\u5f62\u614b\u5b78\u53cd\u61c9\u53ef\u8a55\u4f30\u7684\u60a3\u5152\u4e2d\uff0c\u5728\u5967\u96f7\u5df4\u66ff\u5c3c\u55ae\u85e5\u6cbb\u7642\u7d50\u675f\u6642\uff08EOM\uff09\uff0c2\u4f8b\u9054\u5230CR\u4f34\u4e0d\u5b8c\u5168\u8840\u7d30\u80de\u6062\u5fa9\uff08CRi\uff09\uff0c2\u4f8b\u9054\u5230\u90e8\u5206\u7de9\u89e3\uff08PR\uff09\uff0cORR\uff08CR+CRi\uff09\u70ba33.3%\uff1b\u5728\u5967\u96f7\u5df4\u66ff\u5c3c\u548cLisaftoclax\u806f\u5408\u6cbb\u7642\u7d50\u675f\u6642\uff08EOC\uff09\uff0c5\u4f8b\uff0883.3%\uff09\u9054\u5230CR\uff1b\u57287\u4f8b\u5206\u5b50\u5b78\u53ef\u8a55\u4f30\u7684\u60a3\u5152\u4e2d\uff0c\u67095\uff0871.4%\uff09\u4f8b\u9054\u5230\u4e86MRD\u9670\u6027\uff0c\u5176\u4e2d1\u4f8b\u5728EOM\u9054\u5230\uff0c4\u4f8b\u5728EOC\u9054\u5230\u3002 \u5b89\u5168\u6027\u6578\u64da\uff1a 10\u4f8b\u60a3\u5152\u4e2d\u67096\u4f8b\u7d93\u6b77\u4e86\u2265 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