C-CAR031, galimoto ya GPC3-specific TGFβRIIDN yodzitetezera yokha ya autologous CAR-T

C-CAR031 ndi njira yodzitetezera yokha ya GPC3-targeting chimeric antigen receptor T-Cell (CAR-T), yomwe ikuphunziridwa pochiza HCC. Imachokera ku GPC3-targeting CAR-T yatsopano yopangidwa ndi AstraZeneca pogwiritsa ntchito nsanja yawo yodziwira zida zoteteza zomwe zimapangitsa kuti pakhale kusintha kwa maselo, zomwe zimapangitsa kuti maselo a khansa ayambe kukula, ndipo imapangidwa ndi AbelZeta ku China. C-CAR031 ikupangidwa ku China pansi pa mgwirizano wa AbelZeta ndi AstraZeneca.

AbelZeta yalengeza zambiri zachipatala zomwe zikuwonetsa ntchito yoyambirira yolimbana ndi chotupa cha C-CAR031, choteteza thupi cha autologous GPC3 CAR-T, mwa odwala omwe ali ndi khansa ya chiwindi yoopsa, pa Msonkhano Wapachaka wa ASCO 2024

Njira: Kuyesa koyamba kwa kuchuluka kwa mlingo mwa anthu, kotseguka pogwiritsa ntchito njira yofulumira komanso kapangidwe ka i3+3. Madokotala a HCC apamwamba a GPC3+ omwe adalephera kulandira chithandizo cha mzere 1 adalandira njira imodzi yokha ya C-CAR031 post standard lymphodepletion. Mapeto ake ndi chitetezo ndi kulekerera, zina zimaphatikizapo pharmacokinetics ndi mphamvu yoyambirira. Zochitika zoyipa (AEs) zidayesedwa ndi CTCAE 5.0, ndipo cytokine release syndrome (CRS) / immune effector cell-associated neurotoxicity syndrome (ICANS) zidayesedwa motsatira njira ya ASTCT 2019. Yankho lolondola lidayesedwa ndi wofufuza motsatira RECIST 1.1.

Zotsatira: Pofika pa Januware 5, 2024, anthu 24 onse adalandira C-CAR031 infusion pa mlingo wa 4 dose (DLs). Anthu onse anali ndi BCLC stage C HCC, 83.3% (20/24) anali ndi metastasis ya extrahepatic. Chiwerengero chapakati cha mankhwala omwe adagwiritsidwa ntchito kale chinali 3.5 (range 1-6), anthu 23 (95.8%) adalandira ICIs (immunocheckpoint inhibitors) ndi TKIs (tyrosine kinase inhibitors). Anthu onse anali ndi chitetezo. Palibe poizoni woletsa mlingo ndipo ICANS idawonedwa. CRS idawonedwa m'magawo 22 (91.7%) ndi CRS imodzi (4.2%) yokha (G) 3. Ma AE odziwika kwambiri a ≥G3 anali lymphocytopenia (100%), neutropenia (70.8%), thrombocytopenia (37.5%) ndi transaminase elevation (16.7%). Gawo limodzi (4.2%) linali ndi G4 myelosuppression ndipo gawo limodzi (4.2%) linali ndi G3 interstitial pneumonitis pa DL4 yoyambitsidwa ndi G3 CRS. Ma AE onse anali osinthika. Ma pts 22 adawunikidwa kuti agwire ntchito. Kuchepa kwa chotupa kudawonedwa mu 90.9% pts, osati m'zilonda zamkati mwa chiwindi zokha komanso zomwe zili kunja kwa chiwindi ndi kuchepa kwapakati kwa 44.0% (range, 3.4%-94.4%). Chiŵerengero chowongolera matenda chinali 90.9% ndipo chiŵerengero choyankha (ORR) chinali 50.0% pa ma pts a ma DL onse. Mu DL4, ORR inali 57.1%.

Mapeto: Kafukufukuyu adawonetsa chitetezo chodalirika komanso kulimbikitsa ntchito yolimbana ndi chotupa ya C-CAR031 mwa odwala a HCC omwe adachiritsidwa kwambiri.

"Tikulimbikitsidwa ndi zotsatira zoyambirira zachipatala za C-CAR031 mwa odwala omwe ali ndi khansa ya chiwindi (HCC) yapamwamba," adatero Tony (Bizuo) Liu, Wapampando komanso CEO wa AbelZeta. "Deta yoyambirira yomwe yaperekedwa lero imapereka umboni wokwanira wa lingaliro loti lingathe kufotokozeranso njira zochiritsira mu HCC ndi zotupa zina zolimba zomwe zikuwonetsa GPC3."

Wofufuza Wamkulu (PI) wa kafukufukuyu, Pulofesa Tingbo Liang wochokera ku First Affiliated Hospital ku Zhejiang University, anati “C-CAR031 yawonetsa chitetezo chabwino komanso yothandiza kwambiri kwa odwala khansa ya chiwindi omwe ali kumapeto kwa nthawi, omwe nthawi zambiri amakhala ndi njira zochepa zochiritsira. Kuchepa kwa chotupa komwe kwawonedwa mwa odwala ambiri (91.3%) kukusonyeza kuti C-CAR031 ili ndi kuthekera kobweretsa phindu kuchipatala ndikupereka chiyembekezo kwa odwalawa.”

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.

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Zolemba

1.AbelZeta yalengeza zambiri zachipatala zomwe zikuwonetsa ntchito yoyambirira yolimbana ndi chotupa cha C-CAR031, choteteza thupi cha autologous GPC3 CAR-T, mwa odwala omwe ali ndi khansa ya chiwindi yoopsa, pa Msonkhano Wapachaka wa ASCO 2024 - AbelZeta Pharma

2.Kafukufuku wa Gawo Loyamba wa C-CAR031, GPC3-specific TGFβRIIDN armored autologous CAR-T, mwa odwala omwe ali ndi khansa ya chiwindi yoopsa (HCC). | Journal of Clinical Oncology (ascopubs.org)