Julayi 17, 2025 - Innovent Biologics yalengeza kuti Nature Medicine yafalitsa zotsatira za kafukufuku wachipatala wa Gawo 1 wa IBI343, mankhwala atsopano oletsa khansa ya m'mimba (CLDN18.2 ADC), ochizira matenda a khansa ya m'mimba (G/GEJ) adenocarcinoma. Kufalitsidwa mu magazini yodziwika bwino yapadziko lonse lapansi iyi kukuwonetsa kuzindikira kwakukulu kwa kuthekera kwa chithandizochi ndipo kukuwonetsa gawo lina lofunika kwambiri pakupita patsogolo kwa China pakupanga mankhwala atsopano oletsa khansa. Kutengera ndi zomwe zapezeka mu kafukufukuyu, mayeso azachipatala a Gawo 3 m'madera ambiri (G-HOPE-001, NCT06238843) adayambitsidwa mu 2024 kuti apititse patsogolo kuwunika IBI343 ngati njira yotetezeka komanso yothandiza yothandizira odwala omwe ali ndi G/GEJ AC yapamwamba.
Pakadali pano, pali mayesero ambiri azachipatala a ukadaulo watsopano wothana ndi khansa ku China omwe akufuna odwala. Mukafunsira mankhwala ndi ukadaulo watsopano, mutha kulumikizana ndi Dipatimenti Yapadziko Lonse ya Chipatala cha Oncology ku Beijing South Region.
Nambala ya Foni: 4008803716
Chizindikiro cha WeChat: 17801183037
Imelo：myimmnet@163.com
Khansa ya m'mimba ikadali imodzi mwa khansa yofala kwambiri padziko lonse lapansi. Malinga ndi ziwerengero za GLOBOCAN 2022, ili pa nambala 5 ya khansa yofala kwambiri komanso chifukwa chachisanu chachikulu cha imfa zokhudzana ndi khansa padziko lonse lapansi, ndipo pafupifupi milandu 970,000 yatsopano ndi imfa 660,000 pachaka. Chaka chilichonse, China imanena kuti milandu 359,000 yatsopano ndi imfa 260,000 chifukwa cha khansa ya m'mimba, zomwe zikuyimira 37.0% ndi 39.4% ya milandu yonse padziko lonse lapansi, motsatana, zomwe zikuwonetsa kufunikira kwakukulu kwachipatala komwe sikunakwaniritsidwe.
CLDN 18.2 ndi puloteni yolumikizana yomwe imaonekera m'maselo osiyanasiyana a epithelial pa mucosa ya m'mimba pansi pa mikhalidwe yabwinobwino ya thupi. Kafukufuku wakale wasonyeza kuti Claudin18.2 imapezeka kwambiri m'mitundu yosiyanasiyana ya khansa, kuphatikizapo khansa ya m'mimba (60-80%), khansa ya kapamba (50%), khansa ya esophageal (30-50%), ndi khansa ya m'mapapo (40-60%). Kuyang'ana CLDN18.2 ndi ma antibodies a monoclonal (mAbs) ndi ADCs ndi njira yatsopano yodalirika yochizira khansa ya m'mimba.
Kafukufuku wofalitsidwayu ndi mayeso azachipatala apadziko lonse lapansi, apakati pa magawo 1 (ClinicalTrial.gov identifier: NCT05458219) omwe adapangidwa kuti awone chitetezo, kulekerera, komanso kugwira ntchito koyambirira kwa IBI343 mwa odwala omwe ali ndi zotupa zolimba kwambiri. Pakati pa Okutobala 26, 2022, ndi Juni 30, 2024, anthu 116 omwe ali ndi G/GEJ adenocarcinoma yapamwamba adalembetsedwa kuti alandire IBI343 monotherapy (8 ikuwonjezeka ndipo 108 ikuwonjezeka).
Zokhudza IBI343 (Anti CLDN18.2 ADC)
IBI343 ndi mankhwala opangidwa ndi Innovent Biologics omwe amaphatikizana ndi ma cell a khansa omwe amaletsa CLDN18.2, zomwe zimayambitsa CLDN18.2-dependent internalization ya ADC. Akalowa mu selo, cytotoxic payload imatulutsidwa, zomwe zimapangitsa kuti DNA iwonongeke komanso kuti maselo a khansa atuluke. Mankhwala otulutsidwawo amathanso kufalikira kudzera mu plasma nembanemba kuti akafike ndikupha maselo oyandikana nawo, zomwe zimapangitsa kuti "anthu aphe anthu ena".
Monga TOPO1i ADC yatsopano, IBI343 yawonetsa chitetezo chovomerezeka komanso yolimbikitsa zizindikiro zogwira ntchito bwino mu maphunziro azachipatala a Gawo 1. Mphamvu yochiritsira ya IBI343 ikufufuzidwa pakali pano m'mitundu ya zotupa monga khansa ya m'mimba ndi khansa ya kapamba.
Kuyesedwa kwachipatala kwa magawo ambiri a Gawo 3 kwa IBI343 kwa adenocarcinoma ya m'mimba / gastroesophageal junction tsopano kukulemba odwala (G-HOPE-001, NCT06238843). Chizindikiro choyenera chaperekedwa ndi Breakthrough Therapy Designation (BTD) ndi NMPA yaku China.
Kuyesedwa kwachipatala kwa magawo ambiri a Gawo 1 la IBI343 kwa adenocarcinoma yotsogola ya pancreatic ductal kukulembetsanso odwala (NCT05458219). Chizindikiro ichi chalandira Fast Track Designation (FTD) kuchokera ku US FDA ndipo chapatsidwa BTD ndi NMPA yaku China.
IBI343 yawonetsa kuti imalimbikitsa kuyankha kwa chotupa komanso phindu lopulumuka.
Kafukufukuyu adasanthula deta yogwira mtima ya anthu omwe ayesedwa omwe ali ndi kuchuluka kwa CLDN18.2 (≥75% ya maselo otupa omwe ali ndi mphamvu yopaka utoto wa membranous ≥2+ ndi IHC), m'magulu awiri a 6 mg/kg ndi 8 mg/kg.
Pa 6 mg/kg (N=31), odwala 15 anali ndi mayankho ochepa (PR) kuphatikizapo odwala 9 omwe anali ndi ma PR otsimikizika ndi wodwala m'modzi yemwe akuyembekezera kutsimikiziridwa. ORR yotsimikizika inali 29.0% (95% CI: 14.2-48.0) ndipo chiwongolero cha matenda (DCR) chinali 90.3% (95% CI: 74.2-98.0). Mwa odwala 9 omwe anali ndi yankho lotsimikizika, nthawi yapakati yoyankha (DoR) inali miyezi 5.6 (95% CI: 2.8-7.0). Kutsatira kwapakati kunali miyezi 10.6 (95% CI: 9.7-11.5) ya PFS ndi OS. PFS yapakati inali miyezi 5.5 (95% CI: 4.1-7.0). Deta ya OS sinali yokhwima ndi OS yapakati ya miyezi 10.8 (95% CI: 6.8-NC). Pambuyo pa kudulidwa kwa deta, mayankho a wodwala m'modzi wotsala adatsimikizika pa Julayi 26, 2024 ndipo ORR yotsimikizika idasinthidwa kufika pa 32.3% (95% CI: 16.7-51.4).
Pa 8 mg/kg (N=17), odwala 17 omwe anali ndi CLDN 18.2 yokwera kwambiri adayesedwa. Pakati pawo, odwala 9 anali ndi PRs kuphatikiza odwala 8 omwe adatsimikizira PR. ORR yotsimikizika inali 47.1% (95% CI: 23.0-72.2), ndipo DCR inali 88.2% (95% CI: 63.6-98.5). Mwa odwala asanu ndi atatu omwe adatsimikiziridwa kuti adayankha, apakati DoR inali miyezi 5.7 (95% CI: 2.7-NC). Mwa odwala onse a G/GEJ adenocarcinoma omwe anali ndi CLDN18.2 yokwera kwambiri omwe adalandira chithandizo pa 8 mg/kg (N=19, kuphatikiza wodwala m'modzi yemwe adatenga mlingo wokwera komanso odwala 18 omwe adatenga mlingo wokwera), apakati otsatira anali miyezi 8.1 (95% CI: 7.6-8.5) ya PFS ndi OS. PFS yapakati inali miyezi 6.8 (95% CI: 2.8-7.5), ndipo OS yapakati sinafike ndipo zochitika zinachitika mwa odwala 36.8%.
IBI343 yawonetsanso chitetezo chapamwamba
Pakati pa odwala onse omwe ali ndi G/GEJ adenocarcinoma (n=116, kuphatikizapo odwala 8 omwe ali ndi khansa ya m'mimba kuyambira nthawi yomwe mlingo unkakwera), odwala 66.4% (77/116) anali ndi TEAEs za kalasi ya ≥3. Ma TEAE ofala kwambiri a ≥3 (≥35%) anali kuchepa kwa chiwerengero cha neutrophil (28.4%), kuchuluka kwa maselo oyera m'magazi kunachepa (25.9%), ndi kuchepa kwa magazi m'thupi (16.4%). Panali zovuta zochepa kwambiri m'mimba zomwe zinali ndi kalasi ya ≥3, kuphatikizapo 1.7% yokha ya nseru ya kalasi ya ≥3. Palibe matenda a m'mapapo a kalasi iliyonse omwe adanenedwa. Kuopsa kokhudzana ndi chithandizo kunachepetsedwa ndi chithandizo chokwanira chothandizira, ndipo chitetezo chonse chinali chovomerezeka.
Pakadali pano, pali mayesero ambiri azachipatala a ukadaulo watsopano wothana ndi khansa ku China omwe akufuna odwala. Mukafunsira mankhwala ndi ukadaulo watsopano, mutha kulumikizana ndi Dipatimenti Yapadziko Lonse ya Chipatala cha Oncology ku Beijing South Region.
Nambala ya Foni: 4008803716
Chizindikiro cha WeChat: 17801183037
Imelo：myimmnet@163.com
Nthawi yotumizira: Julayi-22-2025