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椋庨櫓
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姝ｆ枃
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鍥捐〃: FDA鍘嗗勾鎵瑰噯涓婂競鐨勬姉浣撹嵂鐗╂暟閲忥紙鎴嚦2020/11/25锛?/em>
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鍥捐〃: 鍏ㄧ悆鍗曟姉甯傚満瑙勬ā锛堜嚎缇庡厓锛?/em>
璧勬枡鏉ユ簮锛欵valuatePharma锛屼腑閲戝叕鍙哥爺绌堕儴
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鍥捐〃: ADC鑽墿鐨勪笁澶у厓浠?/em>
璧勬枡鏉ユ簮锛欰ntibody-drug conjugates: recent advances in conjugation and linker chemistries锛屼腑閲戝叕鍙哥爺绌堕儴
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鍥捐〃: ADC鑽墿鐨勪綔鐢ㄦ満鐞?/em>
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鍥捐〃: ADC鎶€鏈殑杩唬
璧勬枡鏉ユ簮锛歋trategies and challenges for the next generation of antibody-drug conjugates锛屼腑閲戝叕鍙哥爺绌堕儴
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鍥捐〃: 鑾稦DA鎵瑰噯涓婂競鐨凙DC鑽墿
璧勬枡鏉ユ簮锛欶DA锛屽尰鑽瓟鏂癸紝涓噾鍏徃鐮旂┒閮?/em>
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鍥捐〃: 鍏ㄧ悆鐨凥ER2 ADC鑽墿宄板€煎競鍦鸿妯￠娴嬶紙浜跨編鍏冿級锛?035骞达級
璧勬枡鏉ユ簮锛欶DA锛屼腑閲戝叕鍙哥爺绌堕儴
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棣栧厛锛屼粠鍏ㄧ悆鑼冨洿鏉ョ湅锛孉DC琛屼笟鐨勫悎浣滀笌骞惰喘宸叉垚涓虹儹闂ㄦ柟鍚戙€?/strong>鍦?020.11鏈堬紝榛樻矙涓滃甯冧互27.5 浜跨編鍏冪幇閲戞敹璐?VelosBio锛岃幏寰楀叾闈跺悜涓€娆鹃澏鍚?ROR1 鐨凙DC鑽墿VLS-101锛涘湪2020骞?鏈堬紝鍚夊埄寰蜂互210浜跨編鍏冩敹璐簡Immunomedics锛岃幏寰椾簡鍏禩rop-2 ADC鑽墿Trodelvy銆傝繖浜涙渚嬩細杩涗竴姝ユ縺鍙慉DC棰嗗煙鐨勬姇璧勭儹鎯咃紝鍚屾椂鍔犻€熸暣涓涓氱殑鎶€鏈繘姝ャ€?/p>
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鍥捐〃: 宸插湪绾虫柉杈惧厠涓婂競鐨勪富瑕丄DC浼佷笟
璧勬枡鏉ユ簮锛歐IND锛屼腑閲戝叕鍙哥爺绌堕儴
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鍥捐〃: Seattle Genetics鐨勫彂灞曞巻绋?/em>
璧勬枡鏉ユ簮锛歐IND锛屼腑閲戝叕鍙哥爺绌堕儴
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ADC鐨勪紭鍖栬璁℃槸鍋氬ソ宸紓鍖栫殑鍏抽敭
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鎶椾綋鐨勯€夋嫨
鎶椾綋鑳藉灏嗗皬鍒嗗瓙姣掔礌鐗瑰紓鍦伴€掗€佽嚦鑲跨槫缁嗚優澶勶紝浠庤€屽疄鐜扳€滈瓟鏈瓙寮光€濈殑鍔熻兘銆傞鍏堝浜庢姉浣撻澏鐐圭殑閫夋嫨锛屽敖閲忛€夋嫨鑲跨槫缁嗚優鑶滆〃闈㈤珮搴﹁〃杈撅紝姝ｅ父缁嗚優鑶滆〃闈綆琛ㄨ揪鐨勬姉鍘熶负闈剁偣锛岃繖鏍疯兘澶熼檷浣嶢DC鑽墿鐨勫壇浣滅敤锛屾彁楂樻不鐤楃獥鍙ｏ紱鍏舵杈冨揩鐨勫唴鍚為€熺巼鍜屽悎閫傜殑鍐呭悶杞繍閫斿緞锛屽揩閫熸湁鏁堝湴瀹炵幇灏忓垎瀛愬湪鑲跨槫缁嗚優鍐呯殑閲婃斁锛涙渶鍚庢姉浣撳湪涓庡寲鐤楄嵂鐗╁伓鑱斿悗锛岄渶瑕佷粛鑳戒繚鐣欏師鍏堢殑鍗曟姉鎬ц川銆?/p>
鍦ㄧ洰鍓嶅凡涓婂競鐨?0涓狝DC浜у搧涓紝鍏遍澏鍚?涓笉鍚岀殑闈剁偣锛圕D33锛孋D30锛孋D22锛孋D79尾锛孒ER2锛孨ectin-4锛孴rop-2锛孊CMA锛夈€傝繎浜涘勾锛孉DC鑽墿鐮斿彂鐨勭儹鐐瑰凡缁忎粠琛€娑茬槫杞Щ鍒板疄浣撶槫锛屽涓澏鐐瑰湪澶氱鑲跨槫绫诲瀷涓兘灞曠幇鍑轰簡鏋佷匠鐨勬不鐤楁晥鏋滐紝鏈夋垚涓烘柊涓€浠ｅ箍璋辨姉鐧岃嵂鐨勬綔鍔涳紝鍥犳涔熸垚涓轰簡褰撳墠ADC鑽墿鐮斿彂鐨勭劍鐐广€?/p>
鍥捐〃: 涓昏鐨凙DC鍦ㄧ爺闈剁偣鍜屼骇鍝?/em>
璧勬枡鏉ユ簮锛欳linicaltrials锛屼腑閲戝叕鍙哥爺绌堕儴
Linker鐨勯€夋嫨
涓轰簡浣緼DC鑽墿鏈夊ソ鐨勫畨鍏ㄦ€у拰鏈夋晥鎬э紝linker鎶€鏈繀椤昏灏介噺瀹炵幇浠ヤ笅涓変釜鍏抽敭鎬ц川锛?strong>1. 鍦ㄨ娑插惊鐜腑淇濇寔楂樼ǔ瀹氭€э紱2. 鏈夌潃楂樹翰姘存€э紝閬垮厤ADC鑱氶泦浣撶殑浜х敓锛?.闇€瑕佸湪鐩爣鍖哄煙瀹炵幇灏忓垎瀛愭瘨绱犵殑閲婃斁锛屼粠鑰屽彂鎸ョ粏鑳炴潃浼ゆ瘨鎬с€?/strong>
Linker鍙互鍒嗕负鍙垏鍓瞝inker涓庝笉鍙垏鍓瞝inker銆?/strong>瀵逛簬涓嶅彲鍒囧壊鐨刲inker锛孉DC鑽墿鍦ㄨ鍐呭悶杩涘叆婧堕叾浣撳悗锛宭inker涓嶄細琚檷瑙ｏ紝鑰岃繛鎺ョ殑鎶椾綋浼氳闄嶈В涓烘皑鍩洪吀锛屽舰鎴愭皑鍩洪吀-杩炴帴瀛?灏忓垎瀛愭瘨绱犲鍚堢墿锛屼粠鑰屽彂鎸ョ粏鑳炴潃浼や綔鐢ㄣ€備緥缃楁皬鐨凨adcyla鍗抽噰鐢ㄤ簡涓嶅彲鍒囧壊鐨刲inker銆?/p>
瀵逛簬涓嶅彲鍒囧壊鐨刲inker锛屽叾鍦ㄨ娑插惊鐜腑涓€鑸洿涓虹ǔ瀹氾紝浣嗘槸鏈€鍚庝唬璋㈠舰鎴愮殑姘ㄥ熀閰?杩炴帴瀛?灏忓垎瀛愭瘨绱犲鍚堢墿娌℃湁缁嗚優绌块€忔€э紝鍥犳浠呰兘瀵硅偪鐦ゆ姉鍘熼珮琛ㄨ揪鐨勮偪鐦ょ粏鑳炶捣鍒版潃浼や綔鐢紝鑰屽鍛ㄥ洿浣庤〃杈剧殑鑲跨槫缁嗚優鏉€浼や綔鐢ㄦ湁闄愶紝涓嶈兘鍙戞尌bystander鏁堝簲銆?/p>
鍥捐〃: 涓嶅彲鍒囧壊鐨刲inker绫诲瀷
璧勬枡鏉ユ簮锛欰ntibody鈥揹rug conjugates: current status and future directions锛屼腑閲戝叕鍙哥爺绌堕儴
瀵逛簬鍙垏鍓茬殑linker锛屽畠鑳藉鍦ㄧ壒寮傚湴鍦╰arget cell涓鍒囧壊閲婃斁鍑哄皬鍒嗗瓙姣掔礌锛屼粠鑰屽彂鎸ョ粏鑳炴潃浼や綔鐢ㄣ€傚悓鏃堕噴鏀惧嚭鐨勫皬鍒嗗瓙姣掔礌鑳藉閫忚繃缁嗚優杈惧埌闄勮繎浣庤〃杈炬垨鑰呬笉琛ㄨ揪鑲跨槫鎶楀師鐨勮偪鐦ょ粏鑳烇紝鍙戞尌bystander鏁堝簲銆傚彲鍒囧壊鐨刲inker涔熸槸褰撳墠ADC鐮斿彂鐨勭儹鐐广€?/p>
鍙垏鍓茬殑linker涓昏鍙垎涓轰互涓嬩笁绉嶏細
锛?/strong>pH鏁忔劅鍨媗inker锛岃繖绫籰inker鍦ㄨ娑插惊鐜腑锛坧H=7.4锛変腑淇濇寔绋冲畾锛屽湪婧堕叾浣擄紙pH 4.5-5.0锛変腑鑳藉琚垏鍓查噴鏀惧嚭灏忓垎瀛愭瘨绱狅紝杈夌憺鐨凚esponsa锛孖mmunomedics鐨凾rodelvy灏遍噰鐢ㄤ簡璇inker銆?/p>
锛?/strong>閰舵晱鎰熷瀷linker锛屼互Val-Cit澶氳偨linker涓轰唬琛紝杩欑被linker浼氳缁嗚優鍐呯壒瀹氱殑閰舵墍瑁傝В锛岄噴鏀惧嚭灏忓垎瀛愭瘨绱犮€?/p>
锛?/strong>鍙繕鍘熺殑浜岀～鍖栫墿linker锛岃繖绫籰inker鍦ㄨ娑插惊鐜腑淇濇寔绋冲畾锛屽湪鑲跨槫缁嗚優涓笌璋疯儽鐢樿偨锛圙SH锛夊弽搴斾粠鑰岃闄嶈В閲婃斁鍑哄皬鍒嗗瓙姣掔礌銆?/p>
鍥捐〃: 鍙垏鍓茬殑linker绫诲瀷
璧勬枡鏉ユ簮锛欳leavable linkers in antibody鈥揹rug conjugates锛屼腑閲戝叕鍙哥爺绌堕儴
灏忓垎瀛愭瘨绱犵殑閫夋嫨
鐢变簬鑲跨槫缁嗚優琛ㄩ潰鎶楀師鏁扮洰鏈夐檺锛?000-106锛夛紝姣忎釜ADC鍒嗗瓙鎼哄甫鐨勫皬鍒嗗瓙姣掔礌鏁扮洰涔熸湁闄愶紝鍚屾椂鍙桝DC鍒嗗瓙杩涘叆缁嗚優閲婃斁drug鏁堢巼鐨勫奖鍝嶏紝鍥犳瀵笰DC涓皬鍒嗗瓙姣掔礌鐨勬瘨鎬ц姹傝緝楂樸€?/p>
鐩墠涓昏鐨勫皬鍒嗗瓙姣掔礌涓昏鍖呮嫭濂ョ憺浠栨眬绫昏鐢熺墿锛圡MAE銆丮MAF锛夛紝缇庣櫥绱犵被琛嶇敓鐗?锛圖M1锛孌M4锛夛紝PBD锛堝悺鍜苟鑻苟浜屾爱鏉傚崜锛変簩鑱氫綋锛屽崱濂囬湁绱犵瓑銆傜敱浜庝笉鍚岀殑灏忓垎瀛愭瘨绱犵殑缁撴瀯涓庢按婧舵€т笉鍚岋紝鍥犳涓庡叾鍋惰仈鐨刲inker涔熸湁鎵€宸埆銆?/p>
鐢变簬灏忓垎瀛愭瘨绱犵殑楂樻瘨鎬э紝鍏跺湪琛€娑插惊鐜腑琚噴鏀惧彲鑳戒細寮曡捣杈冨ぇ鐨勫壇浣滅敤锛屽綋鍓嶇殑涓€涓儹鐐规槸寮€鍙戜腑绛夋瘨鎬х殑姣掔礌锛堟姂鍒舵椿鎬у湪nM绾у埆锛夛紝濡侱S-8201鐨凞Xd锛屼互鍙奣rodelvy鐨凷N38锛屽悓鏃朵娇鐢ㄩ珮DAR鍊煎伓鑱斻€?/p>
鍥捐〃: 灏忓垎瀛愭瘨绱犵被鍨?/em>
鍋惰仈鏂瑰紡鐨勯€夋嫨
閫氳繃鍚勭涓嶅悓鐨勫伓鑱旀妧鏈兘澶熷皢linker-drug杩炴帴鍒版姉浣撲笂锛岃繖涓€杩囩▼鍐冲畾浜嗘姉浣撲笂杩炴帴姣掔礌鑽墿鐨勪釜鏁帮紙Drug-antibody Ratio锛孌AR锛夛紝涔熷喅瀹氫簡ADC浜х墿鐨勫潎涓€鎬с€?/strong>
鍋惰仈鎶€鏈彲浠ュ垎涓洪殢鏈哄伓鑱斿拰瀹氱偣鍋惰仈銆?/strong>涓€鑸€岃█锛岄殢鏈哄伓鑱旈€夋嫨鎬ц緝宸紝浜х墿涓璂AR鍒嗗竷骞挎硾锛屽潎涓€鎬ц緝宸紝缁機MC鐢熶骇甯︽潵浜嗕竴瀹氶毦搴︼紝鑰屼骇涓氱晫璁や负瀹氱偣鍋惰仈鎶€鏈垯鏈夋湜寰楀埌鍧囦竴鎬ф洿濂界殑浜у搧銆?/p>
璧栨皑閰搁殢鏈哄伓鑱?/strong>鏄竴绉嶆棭鏈熷彂灞曡捣鏉ョ殑鍋惰仈鏂规硶锛屽叾閫夋嫨鎬ц緝宸紝鎶椾綋涓ぇ绾?0-100涓禆姘ㄩ吀鐨勬皑鍩猴紝甯歌鐨勮禆姘ㄩ吀鍋惰仈鍙嶅簲鍖呮嫭浣跨敤鏈夋晥杞借嵎鐨勬椿鎬ч叝锛堥€氬父鏄疧-鐞ョ弨閰颁簹鑳鸿瘯鍓傚NHS锛夊舰鎴愮ǔ瀹氱殑閰拌兒閿€傚凡涓婂競鐨凙DC浜у搧涓紝Kadcyla 锛圖AR~3.5锛夛紝Mylotarg 锛圖AR 2~3锛夊拰Besponsa 锛圖AR~6锛夊潎閲囩敤浜嗚禆姘ㄩ吀闅忔満鍋惰仈銆?/p>
鍥捐〃: 璧栨皑閰搁殢鏈哄伓鑱旂ず鎰忓浘
璧勬枡鏉ユ簮锛歍he chemical design and synthesis of linkers used in antibody drug conjugates锛屼腑閲戝叕鍙哥爺绌堕儴
浜岀～閿繕鍘熷崐鑳辨皑閰稿伓鑱旀槸鐩墠浣跨敤鏈€澶氱殑鍋惰仈鏂瑰紡銆?/strong>浠gG1涓轰緥锛屽叾涓湁4瀵归摼闂翠簩纭敭鍙杩樺師锛岃繕鍘熷悗寰楀埌8涓叿鏈変翰鏍告€ц兘鐨勫崐鑳辨皑閰稿矾鍩恒€侺inker涓婄殑椹潵閰颁簹鑳虹瓑鍩哄洟鑳戒笌宸熀鍙嶅簲锛屽舰鎴愮ǔ瀹氱殑鍋惰仈鐗┿€傞€氳繃浜岀～閿繕鍘熺殑绋嬪害鍙互浼樺寲鏈€缁堜骇鍝佺殑DAR鍊硷紝渚嬪Adcetris 锛圖AR~4锛夛紝Blenrep 锛圖AR~4锛夌殑DAR鍊肩害涓?锛汿rodelvy 锛圖AR~7.6锛夛紝Enhertu 锛圖AR 7~8锛夌殑DAR鍊兼帴杩戜簬8銆?/p>
鍥捐〃: 浜岀～閿繕鍘熷崐鑳辨皑閰稿伓鑱旂ず鎰忓浘
瀹氱偣鍋惰仈鏄綋涓嬬爺鍙戠殑鐑偣锛屾垜浠涓鸿鎶€鏈湁鏈涘緱鍒板潎涓€鎬э紝瀹夊叏鎬ф洿濂界殑ADC浜у搧锛屼粠鑰屾嫇瀹芥不鐤楃獥鍙ｃ€傚畾鐐瑰伓鑱旂殑鍑犵涓昏鎶€鏈寘鎷細
锛?/strong>Thiomab鎶€鏈細璇ユ妧鏈敱鍩哄洜娉板厠寮€鍙戯紝閲囩敤鍩哄洜宸ョ▼鎶€鏈湪鎶椾綋鐗瑰畾浣嶇疆澶勬彃鍏ュ崐鑳辨皑閰告畫鍩猴紝鐒跺悗灏嗗崐鑳辨皑閰镐笂鐨勫矾鍩哄拰鑽墿鍒嗗瓙鍋惰仈锛屽悎鎴愪簡浣嶇偣涓撲竴鐨凙DC浜у搧锛?鍏朵腑鑽墿鎶椾綋姣斾负2鐨勪骇鐗╁崰姣旇秴杩?0锛呫€傝繖绉嶅畾鐐瑰伓鑱旂殑鏂瑰紡鏃笉浼氬共鎵板厤鐤悆铔嬬櫧鎶樺彔鍜岀粍瑁咃紝 涔熶笉浼氭敼鍙樻姉浣撳拰鎶楀師鐨勭粨鍚堟ā寮忥紱 涓斿拰浼犵粺鍋惰仈鎶€鏈緱鍒扮殑ADC鑽墿鐩告瘮锛?浣跨敤Thiomab鎶椾綋鐨凙DC鑽墿鍦ㄤ繚鐣欎綋鍐呮姉鑲跨槫娲绘€х殑鍚屾椂鍙堟彁楂樹簡鑰愬彈鎬с€侀檷浣庝簡绯荤粺姣掓€с€?/p>
鍥捐〃: Thiomab鍋惰仈鎶€鏈ず鎰忓浘
璧勬枡鏉ユ簮锛歋ite-specific conjugation of a cytotoxic drug to an antibody improves the therapeutic index锛屼腑閲戝叕鍙哥爺绌堕儴
锛熻禆姘ㄩ吀瀹氱偣鍋惰仈鎶€鏈細绉戜鸡寮€鍙戜簡鐙湁鐨勮禆姘ㄩ吀瀹氱偣鍋惰仈鎶€鏈钩鍙帮紝鑳藉绋冲畾寰楀埌DAR涓?鐨凙DC浜у搧銆傚熀浜庢骞冲彴寮€鍙戜簡闈跺悜HER2鐨凙DC 浜у搧A166锛岀洰鍓嶆澶勪簬涓村簥闃舵銆?/p>
锛熼潪澶╃劧姘ㄥ熀閰告妧鏈細閫氳繃鐢熺墿姝ｄ氦鍙嶅簲锛屽紩鍏ラ潪澶╃劧姘ㄥ熀閰革紝灏卞繀椤婚噸鏂拌璁′竴濂椾笌涔嬫浜ゅ搴旂殑 tRNA 鍜岄叾銆侫mbrx 灏嗘柊鐨?tRNA / tRNA 鍚堟垚閰舵浜ら泦宸ョ▼鍖栧埌浜嗙粏鑳炵郴涓紝瀹冧滑鍙互鐗瑰紓鎬ц瘑鍒苟鍦ㄦ不鐤楁€ц泲鐧借川涓畾涔夌殑浣嶇疆绮剧‘鍦版彃鍏ラ潪澶╃劧姘ㄥ熀閰搞€備互瀵逛箼閰拌嫰涓欐皑閰镐负渚嬶紝灏嗗叾寮曞叆鍒版姉浣撲笂鍚庯紝鍙互閫氳繃鑲熼敭涓庣粏鑳炴瘨绱犵被鑽墿鍋惰仈锛屽舰鎴愭姉浣撹嵂鐗╁伓鑱旂墿銆?/p>
Ambrx/娴欐睙鍖昏嵂鐨凥ER2 ADC浜у搧ARX788灏遍噰鐢ㄤ簡闈炲ぉ鐒舵皑鍩洪吀鎶€鏈紝鍏禗AR鍊肩害涓?.8銆備笌T-DM1鐩告瘮锛孉RX788鐨勫伐鑹烘帶鍒跺拰鑽墿绋冲畾鎬с€佷綋鍐呬唬璋㈢瓑鍏锋湁寰堝ソ鐨勪紭鍔裤€?/p>
鍥捐〃: 闈炲ぉ鐒舵皑鍩洪吀鎶€鏈ず鎰忓浘
璧勬枡鏉ユ簮锛欰mbrx锛屼腑閲戝叕鍙哥爺绌堕儴
锛熷熀浜庡ぉ鐒剁硸鍩哄寲浣嶇偣鐨凣lycoConnect鎶€鏈細GlycoConnect锛熸槸涓€绉嶇敱Synaffix鍏徃寮€鍙戠殑瀹氱偣鍋惰仈鎶€鏈紝鑳藉鍒╃敤澶╃劧绯栧熀鍖栦綅鐐瑰疄鐜板畾鐐瑰伓鑱斻€侳c鍖哄煙N297绯栧熀鍖栦綅鐐瑰湪閰跺偓鍖栦笅锛屽绯栭摼杩涜鍒囧壊骞惰繛鎺ヤ笂鍙犳爱鍩哄洟锛岀劧鍚庡彔姘熀鍥笌杩炴帴瀛愪笂鐨勭幆杈涚倲閫氳繃SPAAC锛坰train-promoted copper-free click锛夊弽搴旓紝褰㈡垚鍧囦竴鐨凞AR鍊间负2鐨勫伓鑱旂墿銆?/p>
涓婃捣缇庨泤鐝傜敓鐗╁凡涓嶴ynaffix杈炬垚鍚堜綔鍗忚锛屽皢鍒╃敤GlycoConnect鎶€鏈繘琛孉DC鑽墿鐨勫紑鍙戙€?/p>
鍥捐〃: GlycoConnect鍋惰仈鎶€鏈ず鎰忓浘
浠庨涓狝DC鑽墿涓婂競鍒扮幇鍦ㄥ凡缁忚繃浜?0骞达紝ADC鎶€鏈钩鍙颁篃宸茬粡缁忓巻浜嗕笁浠ｅ彉闈╋紝鐩稿叧鎶€鏈笉鏂畬鍠勩€傛垜浠涓哄悎鐞嗕紭鍖栬璁℃湁鏈涘緱鍒板樊寮傚寲鐨勪骇鍝侊紝鎶€鏈殑浼樺寲鍜岃凯浠ｄ篃鏈夋湜甯︽潵瀹夊叏鎬у拰鐤楁晥鏇翠匠鐨凙DC鑽墿銆?/p>
娴峰涓昏ADC鍏徃绠€浠嬶紝骞冲彴浠峰€煎嚫鏄?/strong>
鎴戜滑瀵规捣澶栦笓娉ㄤ簬ADC鑽墿鐮斿彂鐨勫叕鍙歌繘琛屼簡姊崇悊锛屽叾涓ぇ閮ㄥ垎鍏徃鎷ユ湁鐗规湁鐨勬妧鏈钩鍙帮紝杩欎篃鏄叾鍋氬嚭宸紓鍖栦骇鍝佺殑鍏抽敭銆傝繖浜涘叕鍙哥殑鎶€鏈钩鍙颁笌浜у搧鍦ㄤ竴瀹氱▼搴︿笂浠ｈ〃浜咥DC鎶€鏈殑鍓嶆部鍜屽彂灞曪紝瀵逛簬鍥藉唴鐨凙DC鑽墿鐮斿彂浠ュ強鎶曡祫鏈夋寚瀵兼剰涔夈€?/p>
Seattle Genetics
涓昏鎶€鏈钩鍙帮細鍏舵牳蹇冩妧鏈寘鎷ゥ鐟炰粬姹€绫昏鐢熺墿锛圡MAE銆丮MAF锛夛紝浠ュ強鏂板瀷linker鐨勫紑鍙戙€?/p>
涓昏浜у搧锛?/strong>鐩墠Seattle Genetics宸叉湁涓ゆADC浜у搧鑾锋壒涓婂競锛屽垎鍒负闈跺悜CD30鐨凙dcetris锛?011.8鑾锋壒锛岀敤浜庢不鐤楅湇濂囬噾娣嬪反鐦わ級浠ュ強闈跺悜Nectin-4鐨凱adcev锛屼袱鑰呭潎閲囩敤浜嗗彲鍒囧壊鐨剉c-MMAE缁勫悎锛屽叾涓瑼dcetris鍦?019骞寸殑閿€鍞宸茬粡杈惧埌浜?0.81浜跨編鍏冦€傚叾浠栧浜庡悗鏈熺殑ADC浜у搧鍖呮嫭Tisotumab vedotin鍜孡adiratuzumab vedotin銆?/p>
Ladiratuzumab vedotin鏄竴娆鹃澏鍚戦攲绂诲瓙杞繍铔嬬櫧LIV-1鐨凙DC鑽墿銆傛牴鎹甀鏈熴€佸崟鑷備复搴婅瘯楠岀殑缁撴灉锛?0渚嬩笁闃翠钩鑵虹檶鎮ｈ€呮帴鍙?绉嶆不鐤楁柟妗堬紝 ladiratuzumab vedotin鍗曡嵂娌荤枟鐨勫瑙傚搷搴旂巼涓?5锛咃紝涓綅鏃犺繘灞曠敓瀛樻湡涓?1鍛ㄣ€傚彟涓€椤筁adiratuzumab vedotin鑱斿悎甯曞崥鍒╃彔鍗曟姉娌荤枟灞€閮ㄦ櫄鏈熸垨杞Щ鎬NBC鎮ｈ€呯殑Ib/II鏈熺爺绌朵腑锛孫RR涓?4锛咃紙95锛匔I锛?3.4锛?73.4锛咃級銆?/p>
鍦?020骞?鏈堬紝榛樻矙涓滃甯冧笌 Seattle Genetics杈炬垚浜嗗悎浣滃崗璁€傞粯娌欎笢灏嗕粠Seattle Genetics鑾峰緱ladiratuzumab vedotin鐨勫叡鍚屽紑鍙戝拰鍟嗕笟鏉冨埄銆傞粯娌欎笢灏嗗悜鍚庤€呮敮浠?浜跨編鍏冮浠樻锛屽苟杩涜10浜跨編鍏冭偂鏉冩姇璧勶紙200缇庡厓/鑲★級銆傚悎浣滄湡闂达紝Seattle Genetics灏嗘湁璧勬牸鑾峰緱鏈€楂?6浜跨編鍏冪殑閲岀▼閲戯紝鍏朵腑鍖呮嫭8.5浜跨編鍏冪爺鍙戦噷绋嬮噾鍜?7.5浜跨編鍏冮攢鍞噷绋嬬閲戙€?/p>
Tisotumab vedotin鏄敱Seattle Genetics寮€鍙戠殑闈跺悜缁勭粐鍥犲瓙锛圱F锛夌殑ADC鑽墿銆傜粍缁囧洜瀛愶紙TF锛夋槸涓€绉嶅弬涓庤偪鐦や俊鍙蜂紶瀵煎拰琛€绠＄敓鎴愮殑铔嬬櫧璐紝鍦ㄧ粷澶у鏁板棰堢檶鎮ｈ€呭拰璁稿鍏朵粬瀹炰綋鐦わ紙鍖呮嫭鍗靛发銆佽偤銆佽儼鑵恒€佺粨鐩磋偁鍜屽ご棰堥儴鐧岀棁锛変腑杩囧害琛ㄨ揪銆俰nnovaTV 204鐮旂┒鏄竴椤圭敤浜庢敮鎸乀isotumab vedotin鐨勫姞閫熸壒鍑嗙殑鍗曡噦鐮旂┒锛岀敤浜庢不鐤楀鍙戦毦娌诲棰堢檶鎮ｈ€呫€傝瘯楠屼腑101鍚嶆偅鑰呮帴鍙椾簡娌荤枟浜員isotumab vedotin 2.0 mg/kg Q3W鐨勬不鐤楋紝闅忚鏃堕棿10涓湀銆侽RR杈惧埌浜?4锛咃紙24/101锛夛紝鍏朵腑鏈?鍚嶆偅鑰呭彇寰桟R銆侱CR杈惧埌浜?2锛咃紙72/101锛夈€侱OR涓?.3涓湀锛孭FS涓?.2涓湀锛孫S涓?2.1涓湀銆傚畨鍏ㄦ€ф柟闈紝涔嬪墠杈冧负鍏虫敞鐨勭溂閮ㄥ壇浣滅敤鍩烘湰涓鸿交寰紙G1 25锛咃紝G2 27锛咃紝G3 2锛咃級锛屽嚭琛€鍓綔鐢紙G1 24锛咃紝G2 3锛咃紝G3 2锛咃級锛屽懆鍥寸缁忕梾鍙橈紙G1 17锛咃紝G2 9锛咃紝G3 7锛咃級銆?/p>
鍥捐〃: Tisotumab vedotin鐨勭粨鏋勮璁′笌鏈哄埗
璧勬枡鏉ユ簮锛欰DC Therapeutics锛屼腑閲戝叕鍙哥爺绌堕儴
鏇村鐩稿叧鍏徃濡侫DC Therapeutics銆丮ersana Therapeutics銆両mmunoGen绛夊叕鍙哥殑浠嬬粛璇疯姝ｅ紡鎶ュ憡銆?/p>
ADC闈剁偣涓嶆柇鍑烘柊锛屾湁璇炵敓澶氭閲嶇鑽墿鐨勬綔鍔?/strong>
鍦ㄧ洰鍓嶅凡涓婂競鐨?0涓狝DC浜у搧涓紝鍏遍澏鍚?涓笉鍚岀殑闈剁偣銆傝繎浜涘勾锛孉DC鑽墿鐮斿彂鐨勭儹鐐瑰凡缁忎粠琛€娑茬槫杞Щ鍒板疄浣撶槫锛屽洜姝ゆ柊闈剁偣鐨勮繘灞曚篃鏄綋涓婣DC鑽墿鐮斿彂鐨勫叧娉ㄧ偣銆傛垜浠涓猴紝杩欎簺鏂伴澏鐐圭殑寮€鍙戯紝灏嗚繘涓€姝ユ嫇灞曟暣涓狝DC鐨勫競鍦虹┖闂淬€傞鍏堟湁澶氫釜闈剁偣鏄剧ず鍑轰簡娉涚檶绉嶆不鐤楃殑娼滃姏锛屽HER2锛孴rop-2锛孨ectin-4锛孯OR1绛夛紱鍏舵ADC鑽墿鍙互閫氳繃鍏禸ystander鏁堝簲锛屽湪鑲跨槫鎶楀師浣庤〃杈剧殑鎮ｈ€呬腑璧锋晥锛岃繘涓€姝ユ墿灞曢€傚簲鐥囦汉缇わ紱鏈€鍚庤櫧鐒剁幇鍦ˋDC鑽墿涓昏鑱氱劍鍦ㄦ湯绾挎不鐤椾笂锛屼絾鏄叾涔熸湁寰€鍓嶇嚎娌荤枟鎺ㄨ繘鐨勬綔鍔涖€傚洜姝ゆ垜浠涓烘柊闈剁偣ADC鑽墿涓洿鏈夊笇鏈涜癁鐢熷嚭閲嶇鑽墿锛岀洰鍓嶇殑涓村簥寮€鍙戜篃鍊煎緱鍏虫敞銆?/p>
浠nti-HER2 ADC涓轰緥锛?澶氱檶绉嶆不鐤楁綔鍔涙樉鐜?/strong>
鐩墠宸茬粡涓婂競浜嗕袱娆鹃澏鍚慔ER2鐨凙DC浜у搧锛屼负缃楁皬鐨凨adcyla鍜孉Z/绗竴涓夊叡鐨凟nhertu 锛圖S-8201锛夛紝鍏朵腑Kadcyla鍦?019骞寸殑閿€鍞宸茬粡杈惧埌浜?5.72浜跨編鍏冦€侹adcyla鑾锋壒鐨勯€傚簲鐥囧寘鎷櫄鏈烪ER2+涔宠吅鐧岀殑鍚庣嚎娌荤枟浠ュ強鏃╂湡楂樺嵄HER2+鐨勬湳鍚庤緟鍔╂不鐤楋紝鑰孌S-8201鍒欏湪闄や钩鑵虹檶澶栫殑鑲虹檶銆佽儍鐧屻€佺粨鐩磋偁鐧屻€佸翱璺笂鐨檶绛夎偪鐦ょ被鍨嬩腑閮藉睍鐜板嚭浼樺紓鐤楁晥锛屾湁鎴愪负鏂颁竴浠ｅ箍璋辨姉鐧岃嵂鐨勬綔鍔涖€?/p>
鈥滃彶涓婃渶寮衡€滺ER2 ADC鈥斺€擡nhertu 锛圖S-8201锛?/p>
DS-8201鐢辩涓€涓夊叡鐮斿彂锛屽湪2020骞?鏈堬紝闃挎柉鍒╁悍涓庣涓€涓夊叡杈炬垚鍚堜綔鍗忚锛岄樋鏂埄搴蜂互13.5浜跨編鍏冮浠樻+38浜跨編鍏冩敞鍐岄噷绋嬬閲戦+17.5浜跨編鍏冮攢鍞噷绋嬬閲戦寮曡繘杩欐HER2 ADC鑽墿銆侱S-8201浜?019骞?2鏈堣幏FDA鎵瑰噯鐢ㄤ簬鏅氭湡HER2+涔宠吅鐧岀殑娌荤枟锛屽叾鐢ㄤ簬3L HER2+鑳冪檶鎮ｈ€呯殑涓婂競鐢宠涔熷凡缁忓悜FDA閫掍氦銆侱S-8021鍦?020骞村墠涓夊搴︾殑閿€鍞绾︿负1.36浜跨編鍏冦€?/p>
DS-8201浼樺紓鐨勭枟鏁堝緱鐩婁簬鍏朵紭鍖栫殑鍒嗗瓙璁捐銆?/strong>DS-8201閫夌敤浜嗘柊鍨嬬殑鍙垏鍓茬殑浜叉按澶氳偨linker杩炴帴浜嗗叾鏂板瀷姣掔礌DXd锛屽悓鏃堕噰鐢ㄤ簡鍗婅儽姘ㄩ吀鍋惰仈锛屾渶缁堜骇鐗╀腑DAR绾︿负7.7銆傚彲鍒囧壊鐨勪翰姘村鑲絣inker鏃㈤樆姝簡鑱氶泦浣撶殑浜х敓锛屼篃浣緿S-8201鏈夊緢寮虹殑bystander鏁堝簲銆?/p>
鍥捐〃: DS-8201鐨勫垎瀛愮粨鏋?/em>
璧勬枡鏉ユ簮锛氱涓€涓夊叡瀹樼綉锛屼腑閲戝叕鍙哥爺绌堕儴
DS-8021鍦ㄥ涓檶绉嶄腑灞曠幇鍑轰簡浼樺紓鐨勭枟鏁堬細
DESTINY-Breast01鐮旂┒锛圚ER2涓珮琛ㄨ揪涔宠吅鐧岋級锛?/strong>鍏辨湁184渚嬩钩鑵虹檶鎮ｈ€咃紙鎮ｈ€呭熀绾匡細100锛呮帴鍙楄繃鏇插Ε鐝犲拰T-DM1鐨勬不鐤楋紝65.8锛呮帴鍙楄繃甯曞Ε鐝犵殑娌荤枟锛汭HC 3+姣斾緥涓?3.7锛咃級鎺ュ彈5.4mg/kg鐨凞S-8201锛孖CR纭鐨凮RR杈惧埌浜?0.9锛咃紝鍏朵腑鏈?1渚嬶紙6锛咃級鎮ｈ€呬负瀹屽叏缂撹В锛圕R锛夛紝DCR涓?7.3锛咃紝涓村簥鑾风泭鐜囷紙CBR=CR+PR+SD鈮?涓湀锛変负76.1锛咃紝涓綅DOR涓?4.8涓湀锛屼腑浣峆FS锛堟棤杩涘睍鐢熷瓨鏈燂級涓?6.4涓湀锛屼腑浣峅S锛堟€荤敓瀛樻湡锛夋湭杈惧埌锛?骞寸敓瀛樼巼棰勪及涓?6锛呫€傚湪24渚嬭剳杞Щ鎮ｈ€呬腑锛屼腑浣峆FS涓?8.1涓湀锛屼篃灞曠幇鍑轰簡浼樺紓鐨勭枟鏁堛€傚畨鍏ㄦ€ф柟闈紝鏈?3.6锛?锛?5/184锛夌殑鎮ｈ€呭嚭鐜颁簡闂磋川鎬ц偤鐐庯紝鍏朵腑澶у鏁颁负G1-G2锛屼粎鏈?浜轰负G3銆?/p>
鍥捐〃: DS-8201鐨凞ESTINY-Breast01鐮旂┒缁撴灉
璧勬枡鏉ユ簮锛氱涓€涓夊叡瀹樼綉锛孨EJM锛屼腑閲戝叕鍙哥爺绌堕儴
DESTINY-Gastric01鐮旂┒锛?/strong>187鍚嶈儍鐧屾偅鑰呮寜2锛?鍒嗙粍鍒嗗埆鎺ュ彈DS-8201锛?.4mg/kg锛宷3w锛?25浜猴級锛堟偅鑰呭熀绾匡細100锛呮帴鍙楄繃鏇插Ε鐝狅紝75锛呮帴鍙楄繃闆疯帿鍗㈠崟鎶楋紝IHC 3+姣斾緥涓?7锛咃級鎴栧寲鐤楋紙62浜猴級銆傜爺绌剁殑涓昏缁堢偣锛圖S-8201 vs 鍖栫枟锛塐RR涓?1锛?vs 14锛咃紝CR涓?锛?vs 0锛咃紝PR涓?2锛?vs 14锛呫€傛瑕佺粓鐐筸PFS涓?.6 vs 3.5涓湀锛圚R=0.47锛夛紱mOS涓?2.5 vs 8.4涓湀锛圚R=0.59锛夈€備簹缁勫垎鏋愪腑锛屽浜嶪HC 3+鎮ｈ€咃紙n=91锛夛紝ORR涓?8锛咃紝浣嗘槸鍦↖HC 2+/ISH+鎮ｈ€咃紙n=28锛変腑锛孫RR涓?9锛呫€傚畨鍏ㄦ€ф柟闈紝10锛咃紙12/125锛夌殑鎮ｈ€呭嚭鐜颁簡闂磋川鎬ц偤鐐庯紝鍏朵腑2浜轰负G3,1浜轰负G4銆?/p>
鍥捐〃: DS-8201鐨凞ESTINY-Gastric01鐮旂┒缁撴灉
璧勬枡鏉ユ簮锛氱涓€涓夊叡瀹樼綉锛孨EJM锛屼腑閲戝叕鍙哥爺绌堕儴
DESTINY-CRC01鐮旂┒锛?/strong>53鍚岺ER2涓珮琛ㄨ揪/RAS閲庣敓鍨嬬殑CRC鎮ｈ€咃紙鎮ｈ€呭熀绾匡細骞冲潎鎺ュ彈杩?绾挎不鐤楋紝鍏朵腑30.2锛呭厛鍓嶆帴鍙楄繃anti-HER2娌荤枟锛汭HC 3+姣斾緥涓?5.5锛咃紝IHC 2+/ISH+姣斾緥涓?4.5锛咃級鎺ュ彈浜咲S-8201 6.4mg/kg q3w鐨勬不鐤椼€傜爺绌剁殑涓昏缁堢偣ORR涓?5.3锛咃紝鍏朵腑涓€渚婥R锛涙瑕佺粓鐐筸PFS涓?.9涓湀锛宮OS灏氭湭杈惧埌銆傚叾涓浜嶪HC 3+鎮ｈ€咃紙n=40锛夛紝ORR涓?7.5锛咃紝浣嗘槸鍦↖HC 2+/ISH+鎮ｈ€咃紙n=13锛変腑锛孫RR浠呬负7.7锛呫€傚畨鍏ㄦ€ф柟闈紝6.4锛咃紙5/78锛夌殑鎮ｈ€呭嚭鐜颁簡闂磋川鎬ц偤鐐庯紝鍏朵腑2浜轰负G5銆?/p>
鍥捐〃: DS-8201鐨凞ESTINY-CRC01鐮旂┒缁撴灉
璧勬枡鏉ユ簮锛氱涓€涓夊叡瀹樼綉锛孉SCO锛屼腑閲戝叕鍙哥爺绌堕儴
DESTINY-Lung01鐮旂┒锛圚ER2绐佸彉NSCLC鎮ｈ€咃級锛?/strong>42鍚岺ER2绐佸彉鐨凬SCLC鎮ｈ€咃紙鎮ｈ€呭熀绾匡細骞冲潎鎺ュ彈杩?绾挎不鐤楋紝鍏朵腑90.5锛呭厛鍓嶆帴鍙楄繃閾傜被鍖栫枟锛?4.8锛呮帴鍙楄繃PD-锛圠锛?鐤楁硶锛夋帴鍙椾簡DS-8201 6.4mg/kg q3w鐨勬不鐤椼€傜爺绌剁殑涓昏缁堢偣ORR涓?1.9锛咃紝DCR涓?0.5锛咃紱娆¤缁堢偣mPFS涓?4.0涓湀锛宮OS灏氭湭杈惧埌銆傚畨鍏ㄦ€ф柟闈紝11.9锛咃紙5/42锛夌殑鎮ｈ€呭嚭鐜颁簡闂磋川鎬ц偤鐐庯紝鍧囦负G1-G2銆?/p>
鍥捐〃: DS-8201鐨凞ESTINY-Lung01鐮旂┒缁撴灉
璧勬枡鏉ユ簮锛氱涓€涓夊叡瀹樼綉锛孉SCO锛屼腑閲戝叕鍙哥爺绌堕儴
闄や簡涓婅堪鎻愬埌鐨勫洓涓复搴婅瘯楠岋紝DS-8201杩樻湁澶氫釜鍏抽敭涓村簥姝ｅ浜庡紑鍙戜腑锛屼緥濡傜敤浜嶩ER2浣庤〃杈句钩鑵虹檶鎮ｈ€咃紙IHC 2+&锛涳紱ISH-锛屾垨鑰匢CH 1+锛岀害鍗犳暣涓钩鑵虹檶鎮ｈ€呯殑50锛咃級鐨凞ESTINY-Breast04鐮旂┒锛涗笌T-DM1澶村澶寸敤浜庨珮鍗盚ER2+涔宠吅鐧屾偅鑰呯殑Post neo-adjuvant娌荤枟锛圖ESTINY-Breast05鐮旂┒锛夛紱姝ゅ杩樻湁澶氶」鐢ㄤ簬鍓嶇嚎娌荤枟鐨勮仈鍚堢枟娉曚篃姝ｅ湪杩涜涓€?/p>
鑽ｆ槍鐢熺墿RC48
RC48鏄浗鍐呰繘灞曟渶蹇殑鑷富鐮斿彂ADC鑽墿锛屽叾鍦ㄨ儍鐧屼笂鐨勫紑鍙戞渶蹇紝涓婂競鐢宠宸蹭簬2020.8鏈堣幏NMPA鍙楃悊銆傛澶栵紝RC48鍦ㄥ翱璺笂鐨檶閫傚簲鐥囨澶勪簬鍏抽敭涓村簥锛屾湁鏈涗簬鏄庡勾涓婂崐骞村悜NMPA閫掍氦BLA锛屽悓鏃禦C48娌荤枟UC涔熻幏寰椾簡FDA棰佸彂鐨勭獊鐮存€х枟娉曡瀹氥€俁C48鍦ㄤ钩鑵虹檶涓婄殑寮€鍙戜富瑕佽仛鐒︿簬HER2浣庤〃杈句汉缇わ紝鐩墠涔熸澶勪簬鍏抽敭涓村簥銆?/p>
鍦ㄥ垎瀛愮粨鏋勮璁′笂锛屾姉浣撻儴鍒嗛€夌敤浜嗘柊鎶椾綋锛屽HER2鏈夋洿寮虹殑浜插拰鍔涳紝鍚屾椂涔熸湁闈炲父楂樻晥鐨勫唴鍚炴椿鎬э紱linker-drug閫夋嫨浜嗗彲鍒囧壊鐨剉c-MMAE锛屽彲浠ョ壒寮傚湴鍦ㄨ偪鐦ょ粏鑳炶閲婃斁鍑烘潵锛屼篃鑳藉彂鎸ystander鏁堝簲锛涘伓鑱旀柟寮忛€夌敤浜嗛儴鍒嗚繕鍘熷悗鐨勫崐鑳辨皑閰稿伓鑱旓紝鏈€缁堜骇鍝佺殑DAR鍊兼帴杩戜簬4銆?/p>
鍥捐〃: RC48鐨勫垎瀛愮粨鏋?/em>
璧勬枡鏉ユ簮锛欰 novel humanized anti-HER2 antibody conjugated with MMAE exerts potent anti-tumor activity锛屼腑閲戝叕鍙哥爺绌堕儴
鍦≧C48娌荤枟鑳冪檶鐨勫叧閿复搴婄爺绌朵腑锛屽叡绾冲叆127渚嬫棦寰€鎺ュ彈杩?绾挎垨2绾夸互涓婄郴缁熷寲鐤楃殑HER2杩囪〃杈炬櫄鏈熻儍鐧岋紙鍖呮嫭鑳冮绠＄粨鍚堥儴鑵虹檶锛夋偅鑰咃紝鎺ュ彈RC48 2.5mg/kg Q2W鐨勬不鐤椼€傜粨鏋滄樉绀篛RR涓?4.4锛咃紝PFS涓?.1涓湀锛孫S涓?.6涓湀锛屽湪瀹夊叏鎬ф柟闈紝RC48甯歌涓嶈壇浜嬩欢涓虹櫧缁嗚優璁℃暟闄嶄綆銆佽劚鍙戙€佷腑鎬х矑缁嗚優璁℃暟闄嶄綆绛夛紝浠ヨ交涓害涓轰富銆?/p>
鍦≧C娌荤枟灏胯矾涓婄毊鐧岀殑1b鏈熺爺绌朵腑锛屽叡绾冲叆浜?3渚婬ER2涓珮琛ㄨ揪鐨勫翱璺笂鐨檶鎮ｈ€咃紝缁撴灉鏄剧ずORR楂樿揪51.2锛咃紝鐤剧梾鎺у埗鐜嘍CR楂樿揪90.7锛呫€傜洰鍓嶅浗鍐呭灏氭湭鏈夋不鐤桯ER2闃虫€у翱璺笂鐨檶鐨勮嵂鍝佽幏寰椾笂甯傛壒鍑嗭紝RC48鏈夋湜鍦ㄨ棰嗗煙鍋氬嚭绐佺牬銆?/p>
鍥捐〃: RC48鐨勮儍鐧屼复搴婄粨鏋?/em>
璧勬枡鏉ユ簮锛欰SCO 2019锛屽叕鍙稿叕鍛婏紝涓噾鍏徃鐮旂┒閮?/em>
鍥捐〃: RC48鐨勫翱璺笂鐨檶涓村簥缁撴灉
璧勬枡鏉ユ簮锛欰SCO 2020锛屼腑閲戝叕鍙哥爺绌堕儴
娴欐睙鍖昏嵂/Ambrx ARX788
ARX788鐢盇mbrx涓撴湁闈炲ぉ鐒舵皑鍩洪吀瀹氱偣鍋惰仈鎶€鏈紑鍙戝緱鍒帮紝鍏禗AR鍊间负2锛涢噰鐢ㄤ簡涓嶅彲鍒囧壊鐨刲inker鍜屾柊鍨嬪皬鍒嗗瓙姣掔礌AS269锛堥珮鏁坱ubulin鎶戝埗鍓傦級銆傜洰鍓嶆澶勪簬1鏈熶复搴婏紝鍓傞噺鐖潯缁撴灉鏄剧ず锛屽墏閲忓埌1.5mg/kg Q3W鏃舵湭鍑虹幇DLT鍜孧TD锛屽湪瀹夊叏鎬ф柟闈紝鏈?鍚嶆偅鑰呭嚭鐜颁簡鑲洪儴姣掓€э紝鍏朵腑浠?浜轰负G3銆傚湪SABCS 2020骞翠細涓婂叕甯冪殑鏈€鏂扮粨鏋滄樉绀猴紝鎺ュ彈1.5mg/kg鐨勬偅鑰呬腑锛孫RR杈惧埌浜?4锛?锛?4/19锛夛紝DCR鏇存槸楂樿揪100锛呫€?/p>
鍥捐〃: ARX788鐨勪钩鑵虹檶涓村簥I鏈熺粨鏋?/em>
璧勬枡鏉ユ簮锛歋ABCS 2019锛屼腑閲戝叕鍙哥爺绌堕儴
绉戜鸡鑽笟A166
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