Ngomhla we-18 kweyoKwindla, ngo-2025, i-Alphamab Oncology yabhengeza ukuba i-anti-HER2 biparatopic antibody-drug conjugate (ADC) JSKN003 inikwe iBreakthrough Therapy Designation yiZiko loVavanyo lwaMayeza (CDE) leSizwe soLawulo lweeMveliso zezoNyango (i-NMPA). Eli gama lelokunyanga umhlaza wesibeleko we-epithelial ovarian ohlala unganyangeki yiplatinum (PROC), umhlaza we-primary peritoneal, okanye umhlaza we-fallopian tube, ongaphelelanga kumanqanaba okubonakaliswa kwe-HER2 kuphela.
Ukunikezelwa kweBreakthrough Therapy Designation kusekelwe kuhlalutyo oludibeneyo lwezifundo ezimbini zeklinikhi, i-JSKN003-101 kunye ne-JSKN003-102. I-JSKN003-101 (NCT05494918) luphononongo lweklinikhi lweSigaba I oluvulelekileyo, oluneendawo ezininzi, oluqhutywa e-Australia, lubhalisa izigulane ezinee-tumor eziqinileyo ezibonisa i-HER2 (IHC≥1+) okanye ezine-HER2 mutations. I-JSKN003-102 (NCT05744427) luphononongo lweSigaba I/II oluqhutywa eTshayina. Inxalenye yeSigaba I ibhalise izigulane ezine-hertologically confirmed HER2 expression (IHC≥1+) okanye i-HER2 mutations eziqinileyo eziphuculweyo. Inxalenye yeSigaba II ibhalise izigulane ezinee-tumor eziqinileyo eziphuculweyo kungakhathaliseki ukuba i-HER2 expression okanye imeko ye-mutation injani.
Idatha yokuqala evela kuhlalutyo oludibeneyo lwale zifundo zimbini iboniswe kwiNgqungquthela yaseYurophu ye-2024 ye-Oncology yezonyango (ESMO).
Ukusukela nge-15 kaJulayi 2024, izigulane ezingama-50 ezine-PROC zifumene i-JSKN003 kumanqanaba amahlanu edosi, phakathi kwazo izigulane ezi-2 kwidosi ye-4.2mg/kg, izigulane ezi-2 kwidosi ye-5.2mg/kg, izigulane ezingama-44 kwidosi ye-6.3mg/kg, isigulane esi-1 kwidosi ye-7.3mg/kg, kunye nesigulane esi-1 kwidosi ye-8.4mg/kg. Phakathi kwezigulane ezingama-50 ezibhalisiweyo ngokusekelwe kuvavanyo lwelabhoratri ephakathi, bekukho izigulane ezili-17 ezine-HER2 expression (IHC 1+, 2+ kunye ne-3+) (izigulane ezi-2 kuphela ezine-HER2 IHC 3+), izigulane ezili-17 ezine-IHC 0, kunye nezigulane ezili-16 azizange zibe neziphumo ze-HER2 kuba bezingakhange zivavanywe ngoJulayi 15. Izigulane ezingama-28 (56.0%) bezineendlela ezintathu ubuncinane zonyango olucwangcisiweyo ngaphambili, izigulane ezingama-37 (74.0%) zifumene unyango lwe-bevacizumab, kwaye izigulane ezingama-28 (56.0%) zifumene unyango lwe-PARP inhibitor.
Ubude obuphakathi bonyango bebuyiiveki ezili-12.4 (uluhlu: iiveki ezingama-0.7 – 51.0), kunye nezigulana ezingama-32 (64.0%) ezisele zisekunyangweni de kwaba ngumhla wokugqibela wedatha.
Ukhuseleko: Phakathi kwabo bonke abaguli abangama-50 ababhalisiweyo, abaguli aba-3 bafumene isifo semiphunga esingaphakathi kwe-interstitial (ILD)/pneumonitis. Abaguli aba-5 (10.0%) bafumene iziganeko ezimbi ezinxulumene nonyango lwebanga lesi-3 (ii-TRAE), ezona zixhaphakileyo zilurhudo (2.0%) kunye ne-anemia (2.0%). Akukho TRAEs zikhokelele ekufeni.
Ukusebenza kakuhle: Phakathi kwezigulane ezingama-44 ezivavanyiweyo ukusebenza kakuhle ezazivavanywe ubuncinane olunye uvavanyo lwe-tumor emva kwesiseko, izinga lokuphendula elijolise ngqo (ORR) yayiyi-56.8%, kunye nezigulane ezingama-39 (88.6%) ezibonisa ukuncipha kwe-tumor. I-ORR kwizigulane ezine-HER2 IHC 0 kunye ne-HER2 expression eqinisekisiweyo (IHC 1+, 2+ kunye ne-3+) yayiyi-52.9% kunye ne-68.8%, ngokwahlukeneyo. Kwizigulane ezingama-33 ezafumana unyango lwe-bevacizumab ngaphambili i-ORR yayiyi-54.5%, kwizigulane ezingama-26 ezafumana unyango lwe-PARP inhibitor ngaphambili i-ORR yayiyi-46.2%.
Iziphumo ezidityanisiweyo zibonise ukuba i-JSKN003 monotherapy inokunyamezelana okuhle kunye neprofayili yokhuseleko, kunye neempawu ezisebenzayo ezithembisayo kwizigulane ezine-PROC ephucukileyo, kwaye ukusebenza kakuhle kubonwe kwizigulane ezine-(IHC 1+/2+3+) okanye ezingenayo (IHC 0) HER2 expression, kunye okanye ngaphandle kwayo ngaphambili i-bevacizumab kunye ne-PARP inhibitor yangaphambili.
Malunga neJSKN003
I-JSKN003 yi-anti-HER2 bispecific antibody-drug conjugate (bis-ADC), eyenziwe ngaphakathi ngeqonga le-Alphamab's proprietary Glycan-specific conjugation. I-JSKN003 inokubopha i-HER2 kumphezulu weeseli ze-tumor kwaye ikhuphe i-topoisomerase I inhibitors (TOPIi) nge-cellular endocytosis, ngaloo ndlela inika iziphumo zokulwa ne-tumor. Xa ithelekiswa nezinye i-ADC, i-JSKN003 ibonakalise uzinzo olungcono lwe-serum kunye nesiphumo esinamandla sokulinda, nto leyo eyandisa ngempumelelo ithuba lonyango.
Okwangoku, kusekho iimvavanyo ezininzi zeklinikhi zobuchwepheshe obutsha bokulwa nomhlaza eTshayina obufuna izigulane. Iingcebiso ngamayeza amatsha kunye nobuchwepheshe, ungaqhagamshelana neSebe leMicimbi yeZibhedlele ze-Oncology zaseBeijing South Region.
Inombolo yefowuni: 4008803716
Email：myimmnet@163.com
Iireferensi
1. https://www.cde.org.cn/main/xxgk/listpage/9f9c74c73e0f8f56a8bfbc646055026d
2.https://www.alphamabonc.com/en/
Ixesha leposi: Matshi-18-2025