Julayi 17, 2025 – I-Innovent Biologics imemezele ukuthi i-Nature Medicine ishicilele imiphumela yocwaningo lwezokwelapha lweSigaba 1 lwe-IBI343, i-anti-CLDN18.2 ADC entsha, yokwelapha i-advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma. Ukushicilelwa kule magazini yezemfundo yamazwe ngamazwe ehamba phambili kubonisa ukuqashelwa okunamandla kwamandla okwelapha okwelashwa futhi kuphawula esinye isigameko esibalulekile entuthukweni yaseShayina ekuthuthukiseni imithi emisha yokulwa nomdlavuza. Ngokusekelwe emiphumeleni yocwaningo, isivivinyo sezokwelapha seSigaba 3 sezifunda eziningi (G-HOPE-001, NCT06238843) saqalwa ngo-2024 ukuze kuhlolwe kabanzi i-IBI343 njengendlela yokwelapha ephephile nephumelelayo yeziguli ezine-G/GEJ AC ethuthukisiwe.
Njengamanje, kusenezivivinyo eziningi zemitholampilo zobuchwepheshe obusha bokulwa nomdlavuza eShayina ezifuna iziguli. Ukubonisana ngemithi emisha kanye nobuchwepheshe, ungaxhumana noMnyango Wezizwe Ngezizwe Wesibhedlela iBeijing South Region Oncology.
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Umdlavuza wesisu usalokhu ungomunye wezimila eziyingozi ezivame kakhulu emhlabeni. Ngokwezibalo ze-GLOBOCAN 2022, ubekwe njengomdlavuza wesihlanu ovame kakhulu kanye nembangela yesihlanu ehamba phambili yokufa okuhlobene nomdlavuza emhlabeni jikelele, ngamacala amasha alinganiselwa ku-970,000 kanye nokufa okungu-660,000 minyaka yonke. Unyaka ngamunye, iShayina ibika amacala amasha angu-359,000 kanye nokufa okungu-260,000 ngenxa yomdlavuza wesisu, okumelela u-37.0% kanye no-39.4% wenani lomhlaba wonke, ngokulandelana, okugqamisa isidingo esikhulu sezokwelapha esingakahlangatshezwa.
I-CLDN 18.2 iyiprotheni ehlanganisiwe ebonakala kumaseli e-epithelial ahlukene ku-mucosa yesisu ngaphansi kwezimo ezijwayelekile zomzimba. Izifundo zangaphambilini zembule ukuthi i-Claudin18.2 ibonakala kakhulu ezinhlotsheni eziningi zomdlavuza, okuhlanganisa umdlavuza wesisu (60-80%), umdlavuza we-pancreatic (50%), i-esophageal carcinoma (30-50%), kanye nomdlavuza wamaphaphu (40-60%). Ukuqondisa i-CLDN18.2 ngama-antibodies e-monoclonal (mAbs) nama-ADC kumelela indlela entsha ethembisayo yokwelapha umdlavuza wesisu.
Lolu cwaningo olushicilelwe luwuvivinyo lwezokwelapha lweSigaba 1 oluhlanganisa izindawo eziningi emhlabeni wonke (isihlonzi seClinicalTrial.gov: NCT05458219) olwenzelwe ukuhlola ukuphepha, ukubekezeleleka kanye nokusebenza kahle kokuqala kwe-IBI343 ezigulini ezinezimila eziqinile ezithuthukile. Phakathi kuka-Okthoba 26, 2022, kanye noJuni 30, 2024, ingqikithi yabantu abangu-116 abane-G/GEJ adenocarcinoma ethuthukile babhaliselwe ukuthola i-IBI343 monotherapy (eyenyuka ngo-8 kanti iyanda ngo-108).
Mayelana ne-IBI343 (Anti CLDN18.2 ADC)
I-IBI343 iyi-recombinant human anti-CLDN18.2 monoclonal antibody-drug conjugate (ADC) eyakhiwe yi-Innovent Biologics. Ibopha ngqo kumaseli esimila aveza i-CLDN18.2, okubangela ukufakwa kwe-ADC okuxhomeke ku-CLDN18.2. Uma isingaphakathi kweseli, umthwalo we-cytotoxic uyakhishwa, okuholela ekulimaleni kwe-DNA kanye nokuphela kwe-apoptosis yamaseli esimila. Umuthi okhishwe ungasakazeka nakwe-plasma membrane ukuze ufinyelele futhi ubulale amaseli angomakhelwane, okuholela "ekufeni kwabantu ababukele".
Njenge-TOPO1i ADC entsha, i-IBI343 ibonise ukuphepha okubekezelelekayo nokukhuthaza izimpawu zokusebenza kahle kulezi zifundo zezokwelapha zeSigaba 1. Amandla okwelapha e-IBI343 okwamanje ayahlolwa ezinhlotsheni zezimila ezifana nomdlavuza wesisu kanye nomdlavuza we-pancreatic.
Isivivinyo sezokwelapha seSigaba sesi-3 sezifunda eziningi se-IBI343 se-advanced gastric/gastroesophageal junction adenocarcinoma manje sesiqasha iziguli (G-HOPE-001, NCT06238843). Inkomba efanele inikezwe i-Breakthrough Therapy Designation (BTD) yi-NMPA yaseShayina.
Isivivinyo sezokwelapha seSigaba 1 sezifunda eziningi se-IBI343 se-advanced pancreatic ductal adenocarcinoma naso sibhalisa iziguli (NCT05458219). Lesi sibonakaliso sithole i-Fast Track Designation (FTD) evela ku-US FDA futhi sanikezwa i-BTD yi-NMPA yaseShayina.
I-IBI343 ibonise ukuthi ikhuthaza impendulo yesimila kanye nezinzuzo zokusinda.
Ucwaningo luhlaziye idatha yokusebenza kahle kweziguli ezihlolwayo ngokuvezwa okuphezulu kwe-CLDN18.2 (≥75% amaseli esimila anobukhulu bokudaya kwe-membrane ≥2+ yi-IHC), emaqenjini amabili omthamo ka-6 mg/kg no-8 mg/kg.
Ku-6 mg/kg (N=31), iziguli ezingu-15 zazinezimpendulo ezingaphelele (PR) okuhlanganisa iziguli ezingu-9 ezine-PR eziqinisekisiwe kanye nesiguli esingu-1 esilinde ukuqinisekiswa. I-ORR eqinisekisiwe yayingu-29.0% (95% CI: 14.2-48.0) kanti izinga lokulawula isifo (DCR) lalingu-90.3% (95% CI: 74.2-98.0). Ezigulini ezingu-9 ezazinempendulo eqinisekisiwe, ubude besikhathi esimaphakathi sempendulo (DoR) babuyizinyanga ezingu-5.6 (95% CI: 2.8-7.0). Ukulandelela okumaphakathi kwakuyizinyanga ezingu-10.6 (95% CI: 9.7-11.5) ze-PFS kanye ne-OS. I-PFS emaphakathi yayiyizinyanga ezingu-5.5 (95% CI: 4.1-7.0). Idatha ye-OS yayingakavuthwa nge-OS emaphakathi yamanje yezinyanga ezingu-10.8 (95% CI: 6.8-NC). Ngemva kokunqanyulwa kwedatha, impendulo yesiguli esisodwa esisele yaqinisekiswa ngoJulayi 26, 2024 kanti i-ORR eqinisekisiwe yabuyekezwa yaba ngu-32.3% (95% CI: 16.7-51.4).
Ku-8 mg/kg (N=17), iziguli ezingu-17 ezazine-CLDN 18.2 ephezulu zazihlolwa. Phakathi kwazo, iziguli ezingu-9 zazine-PRs kuhlanganise neziguli ezingu-8 ezaziqinisekisile i-PR. I-ORR eqinisekisiwe yayingu-47.1% (95% CI: 23.0-72.2), kanti i-DCR yayingu-88.2% (95% CI: 63.6-98.5). Ezigulini eziyisishiyagalombili ezazinempendulo eqinisekisiwe, i-DoR ephakathi yayizinyanga ezingu-5.7 (95% CI: 2.7-NC). Kuzo zonke iziguli ze-G/GEJ adenocarcinoma ezine-CLDN18.2 ephezulu eziphathwe ku-8 mg/kg (N=19, kufaka phakathi isiguli esisodwa esivela ekukhuphukeni komthamo kanye neziguli ezingu-18 ezivela ekukhuleni komthamo), ukulandelwa okuphakathi kwakuyizinyanga ezingu-8.1 (95% CI: 7.6-8.5) ze-PFS kanye ne-OS. I-PFS ephakathi nendawo yayizinyanga ezingu-6.8 (95% CI: 2.8-7.5), kanti i-OS ephakathi nendawo ayizange ifinyelelwe lapho kwenzeka izehlakalo ezigulini ezingu-36.8%.
I-IBI343 iphinde yabonisa ukuphepha okuphezulu
Phakathi kwazo zonke iziguli ezine-G/GEJ adenocarcinoma (n=116, kufaka phakathi iziguli ezingu-8 ezinomdlavuza wesisu kusukela esigabeni sokwenyuka komthamo), iziguli ezingu-66.4% (77/116) zazine-TEAE zebanga elingu-≥3. Ama-TEAE ebanga elingu-≥3 avame kakhulu (≥35%) ayenciphile inani lama-neutrophil (28.4%), inani lamaseli amhlophe egazi lehlile (25.9%), kanye ne-anemia (16.4%). Kwakukhona izehlakalo ezimbalwa kakhulu ezimbi zesisu zebanga elingu-≥3, kufaka phakathi u-1.7% kuphela wesicanucanu sebanga elingu-≥3. Akukho sifo samaphaphu esingaphakathi kwanoma yiliphi ibanga esabikwa. Ubuthi obuhlobene nokwelashwa buncishisiwe ngokwelashwa okusekelayo okwanele, futhi ukuphepha okuphelele kwakubekezeleleka.
Njengamanje, kusenezivivinyo eziningi zemitholampilo zobuchwepheshe obusha bokulwa nomdlavuza eShayina ezifuna iziguli. Ukubonisana ngemithi emisha kanye nobuchwepheshe, ungaxhumana noMnyango Wezizwe Ngezizwe Wesibhedlela iBeijing South Region Oncology.
Inombolo yocingo: 4008803716
I-ID ye-WeChat: 17801183037
I-imeyili：myimmnet@163.com
Isikhathi sokuthunyelwe: Julayi-22-2025