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

I-C-CAR031 iyindlela yokwelapha ye-T-T (CAR-T) eqondiswe yi-GPC3, ehlolwayo, efundelwa ukwelashwa kwe-HCC. Isekelwe ku-CAR-T entsha eqondiswe yi-GPC3 eyenzelwe yi-AstraZeneca isebenzisa ipulatifomu yabo yokutholakala kwe-armorring discovery armorring elawula ukukhula kwe-beta-beta receptor II dominant negative (dnTGFβRII) futhi ikhiqizwa yi-AbelZeta eShayina. I-C-CAR031 ithuthukiswa eShayina ngaphansi kwesivumelwano sokuthuthukisana phakathi kwe-AbelZeta ne-AstraZeneca.

I-AbelZeta imemezela idatha yezokwelapha ekhombisa umsebenzi wokuqala wokulwa nomdlavuza we-C-CAR031, i-autologous GPC3 CAR-T ehlonyisiwe, ezigulini ezine-carcinoma yesibindi ethuthukile, eMhlanganweni Waminyaka Yonke we-ASCO ka-2024

Izindlela: Isivivinyo sokuqala esikumuntu, esivulelekile sokwanda komthamo sisebenzisa i-titration esheshisiwe kanye nomklamo we-i3+3. Ama-pts e-HCC athuthukile e-GPC3+ ahlulekile ukwelashwa okujwayelekile komugqa ongu-≥ 1 athole ukumnika okukodwa kwe-iv kwe-C-CAR031 post standard lymphodepletion. Ama-endpoint ayinhloko ukuphepha nokubekezeleleka, amanye afaka phakathi i-pharmacokinetics kanye nokusebenza kahle kokuqala. Izehlakalo ezimbi (ama-AE) zilinganiswe yi-CTCAE 5.0, kanye ne-cytokine release syndrome (CRS) / immune effector cell-associated neurotoxicity syndrome (ICANS) zihlolwe ngokwezindlela ze-ASTCT 2019. Impendulo eqondile ihlolwe ngumphenyi ngokwe-RECIST 1.1.

Imiphumela: Kusukela ngomhlaka-5 Januwari 2024, inani lama-pts angu-24 lathola ukumnika kwe-C-CAR031 kumazinga omthamo angu-4 (ama-DL). Wonke ama-pts ayene-BCLC stage C HCC, ama-83.3% (20/24) ayene-metastasis yangaphandle kwesibindi. Inani elimaphakathi lemigqa yokwelashwa yangaphambili lalingu-3.5 (ububanzi 1-6), ama-pts angu-23 (95.8%) athola ama-ICI (izivimbeli zokuhlola amasosha omzimba) kanye nama-TKI (izivimbeli ze-tyrosine kinase). Wonke ama-pts ahlolwe ngokuphepha. Akukho ubuthi obukhawulela umthamo futhi ama-ICANS abonwe. I-CRS yabonwa kuma-pts angu-22 (91.7%) kuphela ane-1 (4.2%) grade (G) 3 CRS. Ama-≥G3 AE avame kakhulu kwakuyi-lymphocytopenia (100%), i-neutropenia (70.8%), i-thrombocytopenia (37.5%) kanye nokuphakama kwe-transaminase (16.7%). I-pt eyodwa (4.2%) yayine-G4 myelosuppression kanye ne-pt eyodwa (4.2%) yayine-G3 interstitial pneumonitis ku-DL4 ebangelwe yi-G3 CRS. Wonke ama-AE abuyiselwa emuva. Ama-pts angu-22 ahlolwe ukusebenza kahle. Ukuncipha kwezicubu kubonwe kuma-pts angu-90.9%, hhayi kuphela ezilondeni zesibindi kodwa nakwezingaphandle kwesibindi ngokuncipha okumaphakathi okungu-44.0% (ububanzi, 3.4%-94.4%). Izinga lokulawula isifo lalingu-90.9% kanti izinga lokuphendula eliqondile (ORR) lalingu-50.0% kuma-pts azo zonke i-DL. Ku-DL4, i-ORR yayingu-57.1%.

Iziphetho: Ucwaningo lubonise iphrofayili yokuphepha elawulekayo futhi lukhuthaza umsebenzi wokulwa nomdlavuza we-C-CAR031 ezigulini ze-HCC eziphathwe kabi kakhulu.

“Sikhuthazwa yimiphumela yokuqala yezokwelapha ye-C-CAR031 ezigulini ezine-hepatocellular carcinoma (HCC) ezithuthukile,” kusho uTony (Bizuo) Liu, uSihlalo kanye ne-CEO ye-AbelZeta. “Imininingwane yokuqala eyethulwe namuhla inikeza ubufakazi obuqand’ ikhanda bomqondo wokuchaza kabusha izindlela zokwelapha ku-HCC kanye nezinye izimila eziqinile eziveza i-GPC3.”

Umphenyi Oyinhloko (PI) walolu cwaningo, uSolwazi Tingbo Liang wase-First Affiliated Hospital yaseZhejiang University, uthe “I-C-CAR031 ibonise iphrofayili enhle yokuphepha kanye nokusebenza kahle okuthembisayo ezigulini ezine-hepatocellular carcinoma esesigabeni sokugcina, ezivame ukuba nenani elilinganiselwe lezinketho zokwelapha ezitholakalayo. Ukuncipha kwesimila okubonwe eningini elikhulu/eliningi (91.3%) leziguli kusikisela ukuthi i-C-CAR031 inamandla okuletha inani lezokwelapha futhi inikeze ithemba kulezi ziguli.”

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-imeyili：myimmnet@163.com

Izinkomba

1.I-AbelZeta imemezela idatha yezokwelapha ekhombisa umsebenzi wokuqala wokulwa nomdlavuza we-C-CAR031, i-autologous GPC3 CAR-T ehlonyisiwe, ezigulini ezine-carcinoma yesibindi ethuthukile, eMhlanganweni Waminyaka Yonke we-ASCO ka-2024 - I-AbelZeta Pharma

2.Ucwaningo lwesigaba sokuqala lwe-C-CAR031, i-GPC3-specific TGFβRIIDN armored autologous CAR-T, ezigulini ezine-carcinoma ye-hepatocellular ethuthukisiwe (i-HCC). | Ijenali ye-Clinical Oncology (ascopubs.org)