PERTUZUMAB + TRASTUZUMAB + HYALURONIDASE

主成分: PERTUZUMAB;TRASTUZUMAB;HYALURONIDASE-ZZXF (~ 357 kDa = 148 kDa + 148 kDa + 61 kDa)

商品名: PHESGO

中文名: 賀雙妥皮下注射劑

美國食品藥物管理局首次核准時間與編號: 2020.06.29 [BLA #761170]

歐盟藥品管理局首次核准時間與編號: 2020.12.21 [EMEA/H/C/005386]

研發廠商: HOFFMANN-LA ROCHE—GENENTECH藥廠(美國)/HOFFMANN-LA ROCHE藥廠(歐盟)

生物製劑序列:

• PERTUZUMAB: (EVQLVESGGGLVQPGGSLRLSCAASGFTFTDYTMDWVRQAPGKGLEWVADVNPNSGGSIYNQRFKGRFTLSVDRSKNTLYLQMNSLRAEDTAVYYCARNLGPSFYFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK)*2 + (DIQMTQSPSSLSASVGDRVTITCKASQDVSIGVAWYQQKPGKAPKLLIYSASYRYTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYYIYPYTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC)*2

• TRASTUZUMAB: (EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK)*2 + (DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC)*2

• HYALURONIDASE: LNFRAPPVIPNVPFLWAWNAPSEFCLGKFDEPLDMSLFSFIGSPRINATGQGVTIFYVDRLGYYPYIDSITGVTVNGGIPQKISLQDHLDKAKKDITFYMPVDNLGMAVIDWEEWRPTWARNWKPKDVYKNRSIELVQQQNVQLSLTEATEKAKQEFEKAGKDFLVETIKLGKLLRPNHLWGYYLFPDCYNHHYKKPGYNGSCFNVEIKRNDDLSWLWNESTALYPSIYLNTQQSPVAATLYVRNRVREAIRVSKIPDAKSPLPVFAYTRIVFTDQVLKFLSQDELVYTFGETVALGASGIVIWGTLSIMRSMKSCLLLDNYMETILNPYIINVTLAAKMCSQVLCQEQGVCIRKNWNSSDYLHLNPDNFAIQLEKGGKFTVRGKPTLEDLEQFSEKFYCSCYSTLSCKEKADVKDTDAVDVCIADGVCIDAFLKPPMETEEPQIFY

公共化合物資料庫(PubChem): 

• Pertuzumab: 不適用/CAS編號: 380610-27-5

• Trastuzumab: 不適用/CAS編號: 180288-69-1

• Hyaluronidase: 不適用/CAS編號: 9001-54-1

英文仿單: U.S. FDA英文仿單 ORIG-1；EMA英文仿單 II/0004

給藥途徑: 皮下注射(subcutaneous injection)

劑量: (1200 mg Pertuzumab + 600 mg Trastuzumab + 30000 U Hyaluronidase)/15 mL；(600 mg Pertuzumab +600 mg Trastuzumab + 20000 U Hyaluronidase)/10 mL

機制: PERTUZUMAB與TRASTUZUMAB均為由中國倉鼠卵巢細胞(Chinese hamster ovary cells)生產之人源化(humanized)抗ERBB2抗體，PERTUZUMAB作用於ERBB2的二聚體結構區塊(dimerization domain)，可阻斷MAPK促分裂原活化蛋白激酶(mitogen-activated protein kinase)與PI3K磷脂肌醇-3-激酶(phosphoinositide 3-kinase)等訊息傳遞而抑制癌細胞增生與誘發細胞凋亡(apoptosis)，TRASTUZUMAB則作用於ERBB2的受體活化結構區塊(receptor activation domain)，可藉由抗體依賴性所產生的細胞毒性(antibody dependent cell mediated cytotoxicity)抑制ERBB2過度表現的癌細胞增生。HYALURONIDASE為透過基因重組將人類SPAM1透明質酸酶(hyaluronidase PH-20)可溶片段嵌入DNA質體，經由中國倉鼠卵巢細胞(Chinese hamster ovary cells)生產的醣苷內切酶(endoglycosidase)，可暫時分解皮下組織胞外基質(extracellular matrix)中的透明質酸(hyaluronan)，使滲透性增加，而增進PERTUZUMAB與TRASTUZUMAB皮下注射時進入體循環的吸收率。

適應症:

1. 乳癌|乳癌(breast cancer):

用於治療ERBB2(HER2)陽性乳癌(breast cancer)，且須符合下述任一條件:

• 與化療併用於前導(neoadjuvant)治療局部晚期發炎性ERBB2(HER2)陽性乳癌(breast cancer)；

• 與化療併用，作為早期(直徑大於2公分或淋巴結陽性)ERBB2(HER2)陽性乳癌完整治療的一部分；

• 與化療併用於輔助(adjuvant)治療具有高復發風險的早期ERBB2(HER2)陽性乳癌(breast cancer)；

• 與docetaxel併用於治療未曾針對轉移性疾病進行抗ERBB2(HER2)療法或化療的轉移性ERBB2(HER2)陽性乳癌(breast cancer)；

潛在靶點與作用機轉: 整理中，敬請期待。 

中華民國藥品許可與健保價格(中文的用法、劑量、副作用等資訊詳見各連結內之仿單資料連結): 

• 研發廠:

  1. 食品藥物管理署衛部菌疫輸字第001172, 001173號之賀雙妥皮下注射劑[瑞士製]:2021.09.22~2026.09.22