I-C-CAR031, i-GPC3-specific TGFβRIIDN armored autologous CAR-T

I-C-CAR031 lunyango lwe-autologous, olune-armored GPC3-targeting chimeric antigen receptor T-Cell (CAR-T), olufundwayo ukuze kunyangwe i-HCC. Isekelwe kwi-GPC3-targeting CAR-T entsha eyilwe yi-AstraZeneca isebenzisa iqonga labo lokufumana izixhobo zokukhusela i-growth factor-beta receptor II dominant negative (dnTGFβRII) kwaye lenziwa yi-AbelZeta eTshayina. I-C-CAR031 iyaphuhliswa eTshayina phantsi kwesivumelwano sophuhliso phakathi kwe-AbelZeta kunye ne-AstraZeneca.

I-AbelZeta ibhengeza idatha yeklinikhi ebonisa umsebenzi wokuqala wokulwa nethumba kwi-C-CAR031, i-autologous GPC3 CAR-T enezixhobo zokulwa, kwizigulana ezine-hepatocellular carcinoma eqhubele phambili, kwiNtlanganiso yoNyaka ye-ASCO ka-2024

Iindlela: Uvavanyo lokuqala oluvela ebantwini, olusebenzisa i-open-label dose-escalation lusebenzisa i-titration ekhawulezileyo kunye noyilo lwe-i3+3. Ii-GPC3+ advanced HCC pts ezingaphumelelanga kunyango oluyi-≥ 1 line systemic zifumene i-iv infusion enye ye-C-CAR031 post standard lymphodepletion. Isiphelo esiphambili kukhuseleko kunye nokunyamezeleka, ezinye ziquka i-pharmacokinetics kunye nokusebenza kwangaphambili. Iziganeko ezimbi (ii-AE) zibekwe kwinqanaba le-CTCAE 5.0, kunye ne-cytokine release syndrome (CRS) / immune effector cell-associated neurotoxicity syndrome (ICANS) zivavanywe ngokweekhrayitheriya ze-ASTCT 2019. Impendulo ejolise ekuhlolweni ihlolwe ngumphandi ngokwe-RECIST 1.1.

Iziphumo: Ukusukela nge-5 kaJanuwari 2024, inani elipheleleyo lama-pts angama-24 afumene i-C-CAR031 infusion kumanqanaba eedosi ezi-4 (ii-DL). Zonke ii-pts zazine-BCLC stage C HCC, i-83.3% (20/24) yayine-metastasis engaphandle kwesibindi. Inani eliphakathi lemigca yangaphambili yonyango yayiyi-3.5 (uluhlu 1-6), ama-pts angama-23 (95.8%) afumene ii-ICI (i-immune checkpoint inhibitors) kunye nee-TKI (i-tyrosine kinase inhibitors). Zonke ii-pts zazivavanywa ukhuseleko. Akukho tyhefu ithintela idosi kwaye i-ICANS yabonwa. I-CRS yabonwa kuma-pts angama-22 (91.7%) kuphela nge-1 (4.2%) grade (G) 3 CRS. Ezona ≥G3 AE zixhaphakileyo yayiyi-lymphocytopenia (100%), i-neutropenia (70.8%), i-thrombocytopenia (37.5%) kunye nokuphakama kwe-transaminase (16.7%). I-pt enye (4.2%) yayine-G4 myelosuppression kunye ne-pt e-1 (4.2%) yayine-G3 interstitial pneumonitis kwi-DL4 ebangelwe yi-G3 CRS. Zonke ii-AE zazinokuguqulwa. Ii-pts ezingama-22 zavavanywa ukuba ziyasebenza na. Ukuncipha kwe-tumor kwabonwa kwi-90.9% pts, kungekuphela nje kwizilonda ze-intrahepatic kodwa nakwi-extrahepatic kunye nokuncipha okuphakathi kwe-44.0% (uluhlu, 3.4%-94.4%). Izinga lokulawula isifo yayiyi-90.9% kwaye izinga lokuphendula elijolise ngqo (ORR) yayiyi-50.0% kwii-pts zazo zonke ii-DL. Kwi-DL4, i-ORR yayiyi-57.1%.

Izigqibo: Olu phononongo lubonise iprofayili yokhuseleko elawulekayo kwaye lukhuthaza umsebenzi we-C-CAR031 wokulwa nethumba kwizigulana ze-HCC ezinyangwe kakhulu.

“Sikhuthazwa ziziphumo zokuqala zeklinikhi ze-C-CAR031 kwizigulana ezine-hepatocellular carcinoma (HCC) eziphucukileyo,” utshilo uTony (Bizuo) Liu, uSihlalo kunye ne-CEO ye-AbelZeta. “Idatha yokuqala evezwe namhlanje inika ubungqina obunamandla bokuchaza kwakhona iindlela zonyango kwi-HCC kunye nezinye iithumba eziqinileyo ezibonisa i-GPC3.”

Umphandi oyiNtloko (PI) wolu phando, uNjingalwazi Tingbo Liang waseSibhedlele iFirst Affiliated kwiYunivesithi yaseZhejiang, uthe “I-C-CAR031 ibonise iprofayili entle yokhuseleko kunye nokusebenza kakuhle okuthembisayo kwizigulana ze-hepatocellular carcinoma ezikwinqanaba lokugqibela, ezihlala zinenani elincinci lonyango olufumanekayo. Ukuncipha kwethumba okubonwayo kwinani elikhulu/elininzi (91.3%) lezigulana kubonisa ukuba i-C-CAR031 inamandla okuzisa ixabiso lezonyango kwaye inike ithemba kwezi zigulana.”

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-imeyile：myimmnet@163.com

Iireferensi

1.I-AbelZeta ibhengeza idatha yeklinikhi ebonisa umsebenzi wokuqala wokulwa nethumba kwi-C-CAR031, i-autologous GPC3 CAR-T enezixhobo zokulwa, kwizigulana ezine-hepatocellular carcinoma eqhubele phambili, kwiNtlanganiso yoNyaka ye-ASCO ka-2024 - I-AbelZeta Pharma

2.Isifundo seSigaba soku-1 se-C-CAR031, i-GPC3-specific TGFβRIIDN armored autologous CAR-T, kwizigulane ezine-advanced hepatocellular carcinoma (HCC). | Ijenali ye-Clinical Oncology (ascopubs.org)