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Ibrutinib (PCI-32765)
IbrutinibÊÇJohnson & JohnsonÓëPharmacyclics Inc.¹²Í¬Ñз¢µÄBTKÒÖÖÆ¼Á£¬ÓÃÓÚÖÎÁƸ´·¢ÐÍ¡¢ÄÑÖÎÐÍÂýÐÔÁܰÍϸ°û°×Ѫ²¡£¨CLL£©ºÍÌ×ϸ°ûÁܰÍÁö£¨MCL£©¡£2011Äê12Ô£¬Johnson & JohnsonÒÔ9.75ÒÚÃÀÔªÂòϸÃÒ©£¬Ä¿Ç°´¦ÓÚIIIÆÚÁÙ´²£¬2013Äê2Ô»ñµÃFDAµÄ¡°Breakthrough Therapy¡±×ʸñ¡£115ÀýMCL»¼Õß¾­ibrutinibÖÎÁƺó£¬×ÜÓ¦´ðÂÊΪ68%£¬22%µÄ»¼ÕßʵÏÖÍêȫӦ´ð¡£ÔÚCLLµÄIIÆÚÁÙ´²ÊÔÑéÖУ¬75%µÄ»¼ÕßÎÞ½øÕ¹Éú´æÆÚ³¬¹ý26¸öÔ£¬83%µÄ»¼Õß×ÜÉú´æÆÚ³¬¹ý26¸öÔ¡£Èç¹û¸ÃÒ©±»Åú×¼ÓÃÓÚCLL¼°ÆäËûÊÊÓ¦Ö¢£¬ÄêÏúÊÛ¶î·åÖµÔ¤¼ÆÎª50ÒÚÃÀÔª¡£


Nivolumab (BMS-936558/ONO-4538/MDX1106)
NivolumabÊÇBristol-Myers Squibb/Ono Pharma¹²Í¬Ñз¢µÄÈ«ÈËÔ´anti-PD1µ¥¿¹£¬ÓÃÓÚÖÎÁƶñÐÔºÚÉ«ËØÁö¡¢·Î°©¡¢Éö°©£¬ÒѽøÈëFDA¿ìËÙͨµÀ£¬Ä¿Ç°´¦ÓÚIIIÆÚÁÙ´²¡£106Àý¶ñÐÔºÚÉ«ËØÁö»¼Õߣ¨107Àý£¿£©¾­1-10mg/kg Q2WÖÎÁƺ󣬿͹ÛÓ¦´ðÂÊΪ31%¡£NivolumabÁªºÏanti-CTLA4µ¥¿¹Ð§¹û¸üºÃ£¬37Àý¶ñÐÔºÚÉ«ËØÁö»¼Õß¾­0.3-3mg/kg nivolumab+3mg/kg ipilimumab Q3WÖÎÁƺ󣬿͹ÛÓ¦´ðÂÊΪ38%£¬ÆäÖÐ17Àý»¼Õß¾­1mg/kg nivolumab+3mg/kg ipilimumab Q3WÖÎÁƺ󣬿͹ÛÓ¦´ðÂÊΪ47%£¨53%£¿£©£¬ÍêȫӦ´ðÂÊΪ18%£¬41%µÄ»¼ÕßÖÎÁÆ12ÖܺóÖ×ÁöËõС80%ÒÔÉÏ¡£


Palbociclib (PD-0332991)
PalbociclibÊÇPfizerÑз¢µÄCDK4/6ÒÖÖÆ¼Á£¬ÓÃÓÚÔÚÖÎÁÆÍíÆÚÈéÏÙ°©£¬2013Äê4Ô»ñµÃFDAµÄ¡°Breakthrough Therapy¡±×ʸñ£¬Ä¿Ç°´¦ÓÚIIIÆÚÁÙ´²£¬Eli LillyµÄͬÀàÒ©ÎïLY2835219´¦ÓÚIIÆÚÁÙ´²¡£36Àý»¼Õß(18ÀýHR+/Her2-¡¢2ÀýHR+/Her2+¡¢8ÀýHR-/Her2-)¾­125mg PD-0332991 QDÖÎÁƺ󣬲¿·ÖÓ¦´ðÂÊΪ7%£¬14%»¼Õß²¡ÇéÎȶ¨6¸öÔÂÒÔÉÏ¡£PD-0332991ÖÎÁÆER+/Her2-¡¢ER+/Her+¡¢ER-/Her2-ÈýÀàÍíÆÚÈéÏÙ°©µÄÎÞ½øÕ¹Éú´æÆÚ·Ö±ðΪ4.1¸öÔ¡¢18.8¸öÔ¡¢1.8¸öÔ¡£PalbociclibĿǰ»¹ÔÚ½øÐÐÕë¶ÔÆäËûÊÊÓ¦Ö¢µÄÁÙ´²ÊÔÑ飬°üÀ¨Âѳ²°©¡¢¶à·¢ÐÔ¹ÇËèÁö¡¢¼±ÐÔÁܰÍϸ°û°×Ѫ²¡¡£


Obinutuzumab (GA101)
ObinutuzumabÊÇGenentechÑз¢µÄÐÂÒ»´úanti-CD20µ¥¿¹£¬ÓÃÓÚÖÎÁÆÂýÐÔÁܰÍϸ°û°×Ѫ²¡£¬Ä¿Ç°´¦ÓÚIIIÆÚÁÙ´²¡£356Àý»¼Õß·Ö³Échlorambucil×é¡¢GA101+ chlorambucil×飬×ÜÓ¦´ðÂÊ·Ö±ðΪ30.2%¡¢75.5%£¬ÍêȫӦ´ðÂÊΪ0¡¢22.2%£¬ÖÐλÎÞ½øÕ¹Éú´æÆÚΪ10.9¸öÔ¡¢23.0¸öÔ£¬rituximab+chlorambucilµÄÈýÏîÖ¸±ê·Ö±ðΪ65.9%¡¢8.3%¡¢15.7¸öÔ¡£2012ÄêrituximabµÄÏúÊÛ¶îΪ71.43ÒÚÃÀÔª£¬obinutuzumabÓÅÓÚrituximab£¬Ç®¾°¿É¹Û¡£


Lambrolizumab (MK-3475)
LambrolizumabÊÇMerckÑз¢µÄÈ«ÈËÔ´anti-PD1µ¥¿¹£¬ÓÃÓÚÖÎÁÆÍíÆÚ¶ñÐÔºÚÉ«ËØÁö£¬2013Äê4Ô»ñµÃFDAµÄ¡°Breakthrough Therapy¡±×ʸñ£¬Ä¿Ç°´¦ÓÚIIÆÚÁÙ´²¡£×÷ÓûúÀíÓëNivolumabÀàËÆ£¬µ«±ÈNivolumabÍíÒ»²½¡£135Àý»¼Õß¾­10mg/kg Q2W¡¢10mg/kg Q3W¡¢2mg/kg Q3WÖÎÁÆºó£¬Æ½¾ù¿Í¹ÛÓ¦´ðÂÊΪ38%¡£ÆäÖÐ57Àý»¼Õß¾­10mg/kg Q2WÖÎÁƺ󣬿͹ÛÓ¦´ðÂÊΪ52%£¬ÍêȫӦ´ðÂÊΪ10%¡£


LDK378
LDK378ÊÇNovartisÑз¢µÄÑ¡ÔñÐÔALKÒÖÖÆ¼Á£¬ÓÃÓÚÖÎÁÆALKÑôÐÔ·ÇСϸ°û·Î°©£¬2013Äê3Ô»ñµÃFDAµÄ¡°Breakthrough Therapy¡±×ʸñ£¬Ä¿Ç°´¦ÓÚIIIÆÚÁÙ´²¡£88Àý»¼Õß¾­400-750mg LDK378 QDÖÎÁƺó£¬×ÜÓ¦´ðÂÊΪ70%£¬¶ÔÓÚ64ÀýcrizotinibÄÍÒ©ÐÍ»¼Õߣ¬×ÜÓ¦´ðÂÊΪ73%¡£¶ÔÓÚÒѾ­È·Ö¤ÓÐÓ¦´ðµÄ»¼Õߣ¬³ÖÐøÓ¦´ðʱ¼äΪ7.4¸öÔ£¬78%µÄ»¼Õß³ÖÐøÓ¦´ðʱ¼äÔÚ6¸öÔÂÒÔÉÏ¡£¶ÔÓÚËùÓÐ123Àý·ÇСϸ°û·Î°©»¼Õߣ¬ÖÐλÎÞ½øÕ¹Éú´æÆÚΪ8.6¸öÔ¡£


Talimogene laherparepvec (T-VEC)
Talimogene laherparepvecÊÇAmgenÑз¢µÄÈÜÁö²¡¶¾£¨2011ÄêÊÕ¹ºBioVax¶øÀ´£©£¬ÓÃÓÚÖÎÁÆÎÞ·¨ÇгýµÄ¶ñÐÔºÚÉ«ËØÁö¡£436Àý»¼Õß·Ö³ÉT-VECÖÎÁÆ×éºÍGM-CSFÖÎÁÆ×飬½á¹ûÏÔʾT-VEC×é¿Í¹ÛÓ¦´ðÂÊΪ26%£¬ÍêȫӦ´ðÂÊΪ11%£¬³ÖÐøÓ¦´ðÂÊΪ16%£¬GM-CSF×é¿Í¹ÛÓ¦´ðÂÊΪ6%£¬ÍêȫӦ´ðÂÊΪ1%£¬³ÖÐøÓ¦´ðÂÊΪ2%¡£


Daratumumab
DaratumumabÊÇJohnson & Johnson¿ª·¢µÄÈ«ÈËÔ´anti-CD38µ¥¿¹£¬ÓÃÓÚÖÎÁƸ´·¢ÐÍ¡¢ÄÑÖÎÐͶ෢ÐÔ¹ÇËèÁö£¬2012Äê8ÔÂJ&JÒÔ11ÒÚÃÀÔª´ÓGenmabÂòÈ룬Ŀǰ´¦ÓÚIIÆÚÁÙ´²£¬ÒÔ½øÈëFDA¿ìËÙͨµÀ£¬2013Äê5Ô»ñµÃ¡°Breakthrough Therapy¡±×ʸñ¡£Daratumumab¶ÔÓÚÆäËûÀàÐ͵ÄѪ°©£¬ÈçÃÖÂþ´óBϸ°ûÐÔÁܰÍÁö¡¢ÂýÐÔÁܰÍϸ°û°×Ѫ²¡¡¢¼±ÐÔÁܰÍϸ°û°×Ѫ²¡¡¢¼±ÐÔËèϸ°û°×Ѫ²¡¡¢ÂËÅÝÐÔÁܰÍÁö¡¢Ì×ϸ°ûÁܰÍÁöµÈ£¬Ò²ÓÐÖÎÁÆÇ±Á¦¡£


Idelalisib (GS-1101)
IdelalisibÊÇGilead SciencesÑз¢µÄPI3K¦ÄÒÖÖÆ¼Á£¬ÓÃÓÚÖÎÁÆÂýÐÔÁܰÍϸ°û°×Ѫ²¡¡¢·Ç»ôÆæ½ðÁܰÍÁö£¬Ä¿Ç°´¦ÓÚIIIÆÚÁÙ´²¡£54ÀýCLL»¼Õß¾­50-350mg QD or BIDÖÎÁƺ󣬿͹ÛÓ¦´ðÂÊΪ56%£¬ÍêȫӦ´ðÂÊΪ4%£¬81%µÄ»¼ÕßʵÏÖÁܰͽáÓ¦´ð¡£ÖÐλÊ×´ÎÓ¦´ðʱ¼äΪ1.9¸öÔ£¬ÖÐλÎÞ½øÕ¹Éú´æÆÚΪ17¸öÔ£¬ÖÐλ³ÖÐøÓ¦´ðʱ¼äΪ18¸öÔ¡£Infinity PharmaµÄPI3K¦Ä/¦ÃÒÖÖÆ¼ÁIPI-145±íÏÖ³öÁ˸üºÃµÄ»îÐÔ¡¢¸üµÍµÄ¸Î¶¾ÐÔ£¬µ«±ÈGileadÍíÒ»²½¡£


MPDL320A (RG7446)
MPDL320AÊÇGenentechÑз¢anti-PDL1µ¥¿¹£¬ÖÎÁÆ×ªÒÆÐÔ¶ñÐÔºÚËØÁö£¬Ä¿Ç°´¦ÓÚIÆÚÁÙ´²¡£anti-PDL1µ¥¿¹Óëanti-PD1µ¥¿¹²»Í¬£¬Ëü²»¸ÉÈÅPDL2ÓëPD1µÄ½áºÏ£¬Òò´Ë¿ÉÄÜûÓзÎÑ×µÈÑÏÖØ¸±·´Ó¦¡£Òѹ«²¼µÄIÆÚÁÙ´²Êý¾ÝÏÔʾ£¬0.01mg/kgÖÁ20mg/kg¼ÁÁ¿ÏÂÄÍÊÜÐÔÁ¼ºÃ£¬ÎÞ¼ÁÁ¿ÏÞÖÆÐÔ¶¾ÐÔ¡£35Àý»¼Õß¾­1-20mg/kg Q3WÖÎÁƺ󣬿͹ÛÓ¦´ðÂÊΪ26%¡£


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