Nge-17 kaJulayi 2025 – I-Innovent Biologics ibhengeze ukuba i-Nature Medicine ipapashe iziphumo zophando lweklinikhi lweSigaba soku-1 se-IBI343, i-anti-CLDN18.2 ADC entsha, yonyango lwe-advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma. Ukupapashwa kweli jenali yezemfundo yamazwe ngamazwe kubonisa ukuqatshelwa okunamandla kwamandla eklinikhi yonyango kwaye kuphawula elinye inqanaba elibalulekileyo kwinkqubela phambili yaseTshayina ekuphuhliseni amayeza amatsha okulwa nethumba. Ngokusekelwe kwiziphumo zophando, uvavanyo lweklinikhi lweSigaba sesi-3 lwemimandla emininzi (G-HOPE-001, NCT06238843) lwaqaliswa ngo-2024 ukuze kuhlolwe ngakumbi i-IBI343 njengokhetho lonyango olukhuselekileyo nolusebenzayo kwizigulane ezine-G/GEJ AC ephucukileyo.
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
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I-imeyile：myimmnet@163.com
Umhlaza wesisu usengomnye wemiphunga enobungozi exhaphakileyo ehlabathini. Ngokwezibalo ze-GLOBOCAN 2022, ubekwe kwindawo yesihlanu exhaphakileyo yesi sifo esinobungozi kunye nesizathu sesihlanu esiphambili sokufa okunxulumene nomhlaza kwihlabathi liphela, kunye namatyala amatsha aqikelelwa kwi-970,000 kunye nokufa kwe-660,000 ngonyaka. Unyaka ngamnye, i-China ibika amatyala amatsha angama-359,000 kunye nokufa kwe-260,000 ngenxa yomhlaza wesisu, okumela i-37.0% kunye ne-39.4% yenani lilonke lehlabathi, ngokulandelelana, nto leyo ebonisa isidingo esikhulu sezonyango esingafezekiswanga.
I-CLDN 18.2 yiprotheyini edibeneyo ebonakala kwiiseli ze-epithelial ezahlukeneyo kwi-mucosa yesisu phantsi kweemeko eziqhelekileyo zomzimba. Izifundo zangaphambili zityhile ukuba iClaudin18.2 ibonakaliswa kakhulu kwiintlobo ezahlukeneyo zomhlaza, kubandakanya umhlaza wesisu (60-80%), umhlaza we-pancreatic (50%), umhlaza we-esophageal (30-50%), kunye nomhlaza wemiphunga (40-60%). Ukujonga i-CLDN18.2 ngee-antibodies ze-monoclonal (mAbs) kunye nee-ADCs kubonisa indlela entsha ethembisayo yokunyanga umhlaza wesisu.
Olu phononongo lupapashweyo luvavanyo lweklinikhi lweSigaba soku-1 oluneendawo ezininzi (i-ClinicalTrial.gov identifier: NCT05458219) oluyilelwe ukuvavanya ukhuseleko, ukunyamezeleka kunye nokusebenza kwangaphambili kwe-IBI343 kwizigulane ezineethumba eziqinileyo eziphucukileyo. Phakathi ko-Okthobha 26, 2022, kunye noJuni 30, 2024, inani lilonke labantu abayi-116 abane-G/GEJ adenocarcinoma ephucukileyo babhaliselwe ukufumana i-IBI343 monotherapy (esi-8 sikhula kwaye i-108 sikhula).
Malunga ne-IBI343 (Anti CLDN18.2 ADC)
I-IBI343 yi-recombinant human anti-CLDN18.2 monoclonal antibody-drug conjugate (ADC) eyenziwe yi-Innovent Biologics. Ibopha ngokukodwa kwiiseli ze-tumor eziveza i-CLDN18.2, ibangela ukufakwa ngaphakathi kwe-ADC okuxhomekeke kwi-CLDN18.2. Nje ukuba ingaphakathi kwiseli, umthwalo we-cytotoxic uyakhutshwa, nto leyo ebangela umonakalo we-DNA kwaye ekugqibeleni i-apoptosis yeeseli ze-tumor. Iyeza elikhutshiweyo linokusasaza kwi-plasma membrane ukuze lifikelele kwaye libulale iiseli ezikufutshane, nto leyo ebangela "isiphumo sokubulala abantu ababukeleyo".
Njenge-TOPO1i ADC entsha, i-IBI343 ibonakalise ukhuseleko olunyamezelekayo kunye nemiqondiso yokusebenza kakuhle kolu phando lwezonyango lweSigaba soku-1. Amandla okunyanga e-IBI343 okwangoku ahlolwa kwiintlobo zeethumba ezifana nomhlaza wesisu kunye nomhlaza wepancreatic.
Uvavanyo lweklinikhi lweSigaba sesi-3 seSigaba sesi-3 oluqhutywa kwiindawo ezininzi lwe-IBI343 ye-advanced gastric/gastroesophageal junction adenocarcinoma ngoku luqesha izigulane (G-HOPE-001, NCT06238843). Isalathisi esifanelekileyo sinikwe iBreakthrough Therapy Designation (BTD) yi-NMPA yaseTshayina.
Uvavanyo lweklinikhi lweSigaba soku-1 seSigaba esininzi se-IBI343 se-advanced pancreatic ductal adenocarcinoma nalo lubhalisa izigulane (NCT05458219). Olu phawu lufumene i-Fast Track Designation (FTD) kwi-US FDA kwaye lunikwe i-BTD yi-NMPA yaseTshayina.
I-IBI343 ibonakalise ukuba ikhuthaza impendulo yesifo se-tumor kunye nenzuzo yokusinda
Olu phononongo luhlalutye idatha yokusebenza kakuhle kwabantu abavavanyiweyo abanokubonakaliswa okuphezulu kwe-CLDN18.2 (≥75% iiseli zethumba ezinobunzulu bokudaya kwe-membrane ≥2+ yi-IHC), kumaqela amabini eedosi ze-6 mg/kg kunye ne-8 mg/kg.
Kwi-6 mg/kg (N=31), izigulane ezili-15 zazineempendulo ezingaphelelanga (PR) kuquka izigulane ezili-9 ezinee-PR eziqinisekisiweyo kunye nesigulane esinye esilinde ukuqinisekiswa. I-ORR eqinisekisiweyo yayiyi-29.0% (95% CI: 14.2-48.0) kwaye izinga lokulawula isifo (DCR) yayiyi-90.3% (95% CI: 74.2-98.0). Kwizigulane ezili-9 ezineempendulo eziqinisekisiweyo, ubude bexesha eliphakathi lempendulo (DoR) yayiyiinyanga ezi-5.6 (95% CI: 2.8-7.0). Ulandelelwano oluphakathi lwaluyiinyanga ezili-10.6 (95% CI: 9.7-11.5) kwi-PFS kunye ne-OS. I-PFS ephakathi yayiziinyanga ezi-5.5 (95% CI: 4.1-7.0). Idatha ye-OS yayingavuthwanga nge-OS ephakathi yangoku yeenyanga ezili-10.8 (95% CI: 6.8-NC). Emva kokunqunyulwa kwedatha, impendulo yesigulana esinye esisele yaqinisekiswa ngoJulayi 26, 2024 kwaye i-ORR eqinisekisiweyo yahlaziywa ukuya kwi-32.3% (95% CI: 16.7-51.4).
Kwi-8 mg/kg (N=17), izigulane ezili-17 ezine-CLDN 18.2 ephezulu ziye zavavanywa. Phakathi kwazo, izigulane ezili-9 zine-PR kuquka izigulane ezisi-8 eziqinisekisile i-PR. I-ORR eqinisekisiweyo yayiyi-47.1% (95% CI: 23.0-72.2), kwaye i-DCR yayiyi-88.2% (95% CI: 63.6-98.5). Kwizigulane ezisibhozo ezinempendulo eqinisekisiweyo, i-median DoR yayiyiinyanga ezi-5.7 (95% CI: 2.7-NC). Kuzo zonke izigulane ze-G/GEJ adenocarcinoma ezine-CLDN18.2 ephezulu ezinyangwe kwi-8 mg/kg (N=19, kuquka isigulane esinye esivela ekunyusweni kwedosi kunye nezigulane ezili-18 ezivela ekwandisweni kwedosi), ukulandelelana okuphakathi bekuyiinyanga ezi-8.1 (95% CI: 7.6-8.5) ze-PFS kunye ne-OS. I-PFS ephakathi yayiziinyanga eziyi-6.8 (95% CI: 2.8-7.5), kwaye i-OS ephakathi ayizange ifikelelwe kwaye iziganeko zenzeke kwizigulane ezingama-36.8%.
I-IBI343 ikwabonakalise ukhuseleko oluphezulu
Phakathi kwazo zonke izigulana ezine-G/GEJ adenocarcinoma (n=116, kuquka izigulana ezisi-8 ezinomhlaza wesisu kwisigaba sokunyusa idosi), izigulana ezingama-66.4% (77/116) zazinee-TEAE zebanga eli-≥3. Ezona ziqhelekileyo ze-TEAE zebanga eli-≥3 (≥35%) zazinciphile inani le-neutrophil (28.4%), inani leeseli ezimhlophe zegazi lehla (25.9%), kunye ne-anemia (16.4%). Zimbalwa kakhulu iziganeko ezimbi zesisu zebanga eli-≥3, kuquka ne-1.7% kuphela yesicaphucaphu sebanga eli-≥3. Akukho sifo semiphunga esiphakathi kwaso nasiphi na inqanaba esixeliweyo. Ubuthi obunxulumene nonyango buncitshisiwe ngonyango olufanelekileyo oluxhasayo, kwaye ukhuseleko luphela lwalunokunyamezeleka.
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
I-ID ye-WeChat: 17801183037
I-imeyile：myimmnet@163.com
Ixesha leposi: Julayi-22-2025