Isingeniso
Ngisho nasezigulini ezifanele ukufakelwa (i-TE), ukwelashwa okujwayelekile komugqa wokuqala kubantu abasengozini enkulu (HR) okusanda kutholwa. i-myeloma eminingi (NDMM) have dismal outcomes. A high-efficacy, safe CAR-T treatment could address this large unmet need. Autologous B cell maturation antigen (BCMA) and CD19 dual-targeting Ukwelashwa kwamaseli e-CAR-T I-GC012F idalwe kusetshenziswa inkundla yokukhiqiza ye-FasTCAR-T yosuku olulandelayo [J Clin Oncol 41, 2023 (suppl; abstr 8005)]. Ucwaningo lwesigaba I sengalo eyodwa lwenziwa kuziguli ze-NDMM ezisengozini enkulu ye-TE ukuze kuhlolwe ukuphepha nokusebenza kwe-GC012F CAR-T cell therapy (NCT04935580). Amaphuzu okuqala ayi-13 anikezwe ku-ASH 2022 (Igazi (2022) 140 (Isengezo 1): 889-890). Sinikeza idatha ebuyekeziwe enokulandelela isikhathi eside kanye neziguli ezengeziwe eziyi-9 (N=22).
Kulandela uhlolo lwesigaba 1, i-GC012F, i-CD19 ehloselwe i-autologous dual-targeted kanye ne-B-cell maturation (BCMA) chimeric antigen receptor (CAR) T-cell therapy, itholwe iyindlela yokwelapha engaphambili ethembisayo yokufakelwa kabusha, enobungozi obukhulu, abasanda kutholwa iziguli eziningi ze-myeloma.1
I-GC012F yeGracell Biotechnologies ibe no-100% ORR kanye no-100% we-MRD-sCR. I-Athene isingathe Umhlangano Waminyaka Yonke wama-20 we-International Myeloma Society (IMS), lapho ibhizinisi lethule khona umbhalo walo.
Indlela
Lokhu isivivinyo somtholampilo isivivinyo esiqalwe umphenyi wesigaba I esinomklamo welebula evulekile kanye nengalo eyodwa. Inkomba yesilingo yi-NCT04935580. Abahlanganyeli abaneminyaka engu-18-70 abanesici esisodwa noma ngaphezulu kwezingenhla bathathwe njengabafanelekele ucwaningo. I-R-ISS-II noma i-R-ISS-III; ukususwa kwe-chromosome 17p, ukudluliselwa phakathi kwama-chromosome 4 no-14, ukudluliselwa phakathi kwama-chromosome 14 no-16, noma ukukhulisa i-chromosome 1q21 okungenani ngamakhophi angu-4; ukuba khona kwe-extramedullary disease (EM); I-IgD noma i-IgE subtype; amazinga e-lactate dehydrogenase (LDH) aphezulu kunomkhawulo ongaphezulu kokujwayelekile; noma ukuhlangabezana nanoma iyiphi inqubo yokuba sengozini enkulu echazwe yi-mSMART3.0.
Lapha, sibika isamba seziguli ezingama-22 ezilinganiselwa eminyakeni yobudala engama-59 (kusukela eminyakeni engama-43 kuye kwengama-69) kusukela ngosuku lokunqanyulwa kwedatha. Isikhawu sesikhathi kusukela ekuxilongeni kuya ekufakweni bekunesilinganiso esiyizinsuku eziyi-100, nebanga lezinsuku ezingama-63 kuye kweziyi-152. Zonke iziguli zazinezici eziyingozi eyodwa noma ngaphezulu, njenge-91% ene-R-ISS isigaba II noma i-III, i-55% enokubandakanyeka okungaphezu kwe-extramedullary (EM), i-32% ibe namakhophi angu-1q21≥4, kanti i-9% inohlobo lwe-IgD.
Ezigulini ezingama-22, ezingama-21 zithole imijikelezo emibili yokwelashwa kokungeniswa nge bortezomib, i-lenalidomide, ne-dexamethasone (VRd), kuyilapho isiguli esisodwa sathola umjikelezo owodwa we-bortezomib, i-epirubicin, ne-dexamethasone (PAD) elandelwa umjikelezo owodwa we-VRd ngaphambi kokumnika. I-GC012F inikezwe njengokufakwa okukodwa kumazinga amathathu ethamo ahlukene: 1×10 5/kg (n=1), 2×10 5/kg (n=4), noma 3×10 5/kg (n=17), kulandela uhlelo olujwayelekile lwezinsuku ezintathu lwe-lymphodepletion oluhlanganisa i-cyclophosphamide ne-fludarabine.
Imiphumela
Okutholwe okokuqala okuvela eqenjini labahlanganyeli abangu-16 ocwaningweni kukhonjiswe ku-2022 American Society for Hematology (ASH) Umhlangano Wonyaka. Iziguli ezintathu ezengeziwe zahlolwa, futhi ukulandelwa kwesikhathi eside kwenziwa eqenjini lokuqala leziguli ze-16. Ukuhlolwa bekuyilebula evulekile, ingalo eyodwa, isilingo esiqaliswe umphenyi wesigaba 1 (IIT) esiphethe i-GC012F kubahlanganyeli kumaleveli edosi athile angu-3. Kuzo zonke iziguli, ama-89% ahlelwe njengesigaba II noma isigaba III, kanti ama-63% ane-extramedullary plasmacytoma.
Ukuphumelela kwesilinganiso sokuphendula esiphelele se-100% (ORR) kanye nesifo esincane esisele (MRD) sokuxazulula iseli elilodwa (scR) kwenzeke phakathi nesikhathi sokulandela esimaphakathi sezinyanga ezingu-15.3 (kusukela ezinyangeni ezingu-3.1 kuya ezinyangeni ezingu-24.5).
"Iziguli ezitholwe zinengozi ephezulu esanda kutholwa i-multiple myeloma (NDMM), okuhlanganisa nalabo abafanelekela ukufakelwa, ngokuvamile zithola imiphumela engagculisi ngokwelashwa kwamanje okujwayelekile," kusho uDkt. Li.1 Frailty, isici esisengozini enkulu, okuhlotshaniswa nenani eliphansi kakhulu lokusinda lika-57% eminyakeni engu-3, uma kuqhathaniswa neziguli ezifanele (enezinga lokusinda lilonke lama-84% eminyakeni engu-3) noma iziguli ezingafanelekile (ezinezinga lokusinda lilonke lama-76% eminyakeni engu-3).
Idatha yabonisa ukuthi iziguli zinezinga eliphezulu lokubekezelela i-GC012F, futhi azikho izinkomba zokuphepha ezinoveli ezitholiwe. Iziguli eziyisithupha zaba ne-mild cytokine release syndrome (CRS). Kulezi zimo, izehlakalo ezi-5 (26%) zichazwe njengebanga loku-1, kanti icala elingu-1 kuphela (5%) lachazwa njengebanga lesi-2. Azikho izehlakalo ze-immune effector cell-associated toxicity (ICANS) zanoma ibuphi ubukhali ezitholiwe.
Both of the two FDA-approved CAR T-cell treatments for refractory or relapsed multiple myeloma cancer have a greater incidence of i-cytokine release syndrome (CRS). The drug I-Ciltacabtagene autoleucel, eyaziwa nangokuthi i-Carvykti, yaqaphela ukuthi i-Cytokine Release Syndrome (CRS) yayikhona ku-95% (92 out of 97) yeziguli. I-Abecma, eyaziwa nangokuthi i-3 Idecabtagene vicleucel, ibangela i-cytokine release syndrome (CRS) ku-85% (108) /127) yeziguli.4
I-GC012F iyahlolwa ezigulini ezinezifo ezihlukahlukene ze-hematological, okuhlanganisa I-B-cell non-Hodgkin lymphoma, ngaphezu kocwaningo lwesigaba 1 olwenziwa ezigulini ezine-myeloma ephindaphindiwe noma ephikisayo.
Mayelana ne-GC012F
I-GC012F iyikhandidethi lomkhiqizo oqondiswe kabili we-CAR-T enikwe amandla nge-FasTCAR i-BCMA/CD19 okwamanje esahlolwayo ezifundweni ze-IIT ku- China for the treatment of multiple myeloma and B-cell non-Hodgkin’s i-lymphoma. GC012F simultaneously targets CD19 and BCMA to drive fast, deep and durable responses, which can potentially improve efficacy and reduce relapse in multiple myeloma and B-NHL patients.
Mayelana ne-FasTCAR
CAR-T cells manufactured on Gracell’s proprietary FasTCAR platform appear younger, less exhausted, and show enhanced proliferation, persistence, bone marrow migration, and isisu cell clearance activities, as demonstrated in preclinical studies. With next-day manufacturing, FasTCAR is able to significantly improve cell production efficiency, which may result in meaningful cost savings, and, together with its fast release time, enable enhanced accessibility of cell therapies for umdlavuza iziguli.
Mayelana noGracell
IGracell Biotechnologies Inc. (“Gracell”) yinkampani yomhlaba wonke ye-biopharmaceutical yesigaba somtholampilo ezinikele ekutholeni nasekuthuthukiseni ukwelapha kwamangqamuzana okuphumelela. Isebenzisa izinkundla zayo zobuchwepheshe ezihamba phambili ze-FasTCAR ne-TruUCAR kanye ne-SMART CARTTM imojuli yobuchwepheshe.
UGracell uthuthukisa ipayipi elicebile lesigaba somtholampilo labakhandidethi bemikhiqizo eminingi ye-autologous kanye ne-allogeneic enamandla okunqoba izinselele ezinkulu zemboni eziqhubekayo nemithi evamile ye-CAR-T, okuhlanganisa izikhathi zokukhiqiza ezinde, ikhwalithi yeseli ephansi, izindleko zokwelapha eziphezulu, nokuntuleka kokwelashwa. zokwelapha ezisebenzayo ze-CAR-T zamathumba aqinile. Ukuze uthole ulwazi olwengeziwe ngoGracell, sicela uvakashele www.gracellbio.com. Landela @GracellBio ku-LinkedIn.
