E nyere Olverembatinib Nhọpụta Ọgwụgwọ Pụrụ Iche maka Ọgwụgwọ nke Ọrịa Leukemia Lymphoblastic dị nkọ nke Philadelphia (Ph+) (ALL)

Na Machị 5, 2025, Ascentage Pharma kwupụtara na Center for Drug Evaluation (CDE) nke National Medical Products Administration (NMPA) nke China enyela ọgwụ ya, olverembatinib, aha Breakthrough Therapy (BTD), maka njikọta ya na obere chemotherapy maka ọgwụgwọ mbụ nke ndị ọrịa a chọpụtara ọhụrụ nwere ọrịa leukemia lymphoblastic acute Philadelphia chromosome-positive (Ph+).

Nke a bụ BTD nke atọ e nyere olverembatinib na China, ya na BTD mbụ e nyere na Machị 2021, maka ọgwụgwọ ndị ọrịa nwere ọrịa leukemia myeloid na-adịghị ala ala (CML-CP) na-eguzogide ma ọ bụ na-anaghị anabata ndị na-egbochi tyrosine kinase (TKIs) nke mbụ na nke abụọ; na BTD nke abụọ e nyere na June 2023, maka ọgwụgwọ ndị ọrịa nwere succinate dehydrogenase (SDH) nke na-enweghị ọrịa eriri afọ (GIST) bụ ndị natara ọgwụgwọ mbụ.

A mara ọkwa na Nzukọ Kwa Afọ nke 66 nke American Society of Hematology (ASH) Safety and Efficacy of Olverembatinib (HQP1351) jikọtara ya na Lisaftoclax (APG-2575) na Ụmụaka na Ndị Ntorobịa nwere Ọrịa Leukemia nke Na-agbanwe Agbanwe/Na-adịghị Alaghachi n'Ọrịa Philadelphia Chromosome–Positive Acute Lymphoblastic (R/R Ph ALL): Akụkọ Mbụ sitere na Ọmụmụ Nkebi nke 1.

Olverembatinib, ọgbọ ọhụrụ nke TKI nke atọ, na-anabata nke ọma ma na-arụ ọrụ siri ike ma na-adịgide adịgide megide kansa ọbara n'ime ndị nwere CP-CML a gwọchara nke ukwuu ma ọ bụ na-enweghị mgbanwe T315I. Lisaftoclax nyocha, ihe mgbochi BCL-2 ọhụrụ, egosila uru ọgwụ mgbochi etuto ahụ na ndị nwere ọtụtụ ọrịa hematologic. Ugbu a, enweghị nhọrọ ọgwụgwọ dị irè dị maka ndị nwere R/R Ph+ ALL. Emebere ọmụmụ ihe a iji nyochaa nchekwa, irè, na profaịlụ pharmacokinetic (PK) nke olverembatinib naanị ma ọ bụ jikọtara ya na lisaftoclax na ụmụaka na ndị ntorobịa nwere R/R Ph ALL.+

Nke a bụ ọmụmụ ihe nke 1b nke e ji aka dee, nke e mere n'oge gara aga (NCT05495035) nke debara aha ụmụaka na ndị ntorobịa dị ihe dịka afọ 18 na-anaghị anabata R/R Ph ALL ma ọ bụ na-anaghị anabata ma ọ dịkarịa ala otu tyrosine kinase inhibitor (TKI) (a naghị atụle ojiji TKI tupu oge eruo ma ọ bụrụ na pts nwere mgbanwe T315I). A chọrọ ka pts nwee akara arụmọrụ Karnofsky/Lansky zuru oke na ọrụ akụkụ ahụ. E wepụrụ pts nwere nsogbu sistemụ akwara etiti ma ọ bụ ọbara ọgbụgba dị ukwuu, nke na-enweghị njikọ na PhALL. A na-enye Olverembatinib ọnụ na 40 mg nke ndị toro eto nhata dose (AED) kwa ụbọchị abụọ maka izu abụọ (Ụbọchị [D] 1-14), wee soro otu dose nke olverembatinib na njikọta ya na lisaftoclax na dose enyere nke 200/400/600 mg (AED) kwa ụbọchị (QD) na D13-42 (a chọrọ mmụba dose ụbọchị atọ site na D13-15). E nyere Dexamethasone 6 mg/m++ n'ọnụ ugboro abụọ n'ụbọchị site na D15-42. Isi ihe ndị dị na njedebe gụnyere nyocha nchekwa, ọnụego nzaghachi zuru oke (ORR), ọnụego adịghị mma nke ọrịa fọdụrụ (MRD), na njirimara PK nke olverembatinib naanị ya/na njikọta ya na lisaftoclax.

Site na Septemba 2022 ruo Juun 2024, e debanyere aha pasent 10. Afọ etiti (oke) bụ afọ 13.0 (11-15), pasent 6 bụkwa ụmụ nwoke. Ibu ahụ etiti (oke) bụ kilogram 49.85 (35.9-86.0). pasent 90.0 gosipụtara transcript p190 na pasent 1 (10.0%) gosipụtara transcript p210. pasent atọ nwere mgbanwe BCR-ABL1 [2, T315I; 1, F317L (c.951C>A)] na ntọala. Mgbe 1 pt kwụsịrị nnwale ahụ n'ihi njide na D1 nke Usoro 1 (C1D1), 9 pts ndị ruru eru gụnyere na ụdị mmụba dose 3+3 (n = 6, R/R; n = 3, enweghị ndidi): 3 pts na Arm ọ bụla (A, B, na C) na ọkwa dose lisaftoclax enyere nke 200, 400, na 600 mg (AED), n'otu n'otu. Ndị a mechara ụbọchị 42 nke ọgwụgwọ ma nyochaa maka isi ihe ndị bụ isi. Isii n'ime 10 pts nwetara ọkwa ≥ 3 nke ọgwụgwọ hematologic - ihe omume ọjọọ na-apụta, gụnyere anaemia (3/10), neutropenia (7/10), na thrombocytopenia (3/10); 1 pt nwere mmụba alanine aminotransferase nke ọkwa 3 nke na-eduga na ịkwụsị ọgwụgwọ, 1 pt nwere ọdịdọ na C1D1 (onye kwụsịrị nnwale ahụ). N'ime ihe nrite isii a tụlere maka mmeghachi omume morphologic, ORR (mgbaghara zuru oke [CR] + CR na mgbake ọnụọgụgụ ezughi oke), mmeghachi omume nkebi, na enweghị ọnụego nzaghachi, n'otu n'otu, 2 (33.3%), 2 (33.3%), na 2 (33.3%) na njedebe nke olverembatinib monotherapy (EOM) na 5 (83.3%), 0, na 1 (16.7%) na njedebe nke usoro ọgwụgwọ olverembatinib na lisaftoclax (EOC). Ise n'ime ihe nrite asaa a na-enyocha ruru ihe ọjọọ MRD, nke 1 dị na EOM na 4 na EOC. Nyocha PK mbụ gosipụtara njirimara PK yiri ya na mkpughe yiri ya n'etiti ụmụaka na ndị toro eto maka olverembatinib na lisaftoclax. Enweghị nnukwu mkpokọta mgbe ejiri ọtụtụ ọgwụ mee ihe, a hụghịkwa mmekọrịta ọgwụ na ọgwụ n'etiti olverembatinib na lisaftoclax.

Ihe ndị a e ji mee nchọpụta mbụ gosiri na olverembatinib na lisaftoclax yiri ka ọ bụ usoro dị mma ma dị irè maka ndị ọrịa nwere R/R Ph ALL. Usoro a butere ọnụego CR dị mma na-enweghị chemotherapy siri ike ma ọ bụ immunotherapy. Ọmụmụ ihe a dị ugbu a na usoro mmụba dose.

Ugbu a, enwere ọtụtụ nnwale ahụike nke teknụzụ ọhụrụ na-egbochi kansa na China na-achọ ndị ọrịa. Maka ndụmọdụ gbasara ọgwụ na teknụzụ ọhụrụ, ị nwere ike ịkpọtụrụ Ngalaba Mba Nile nke Ụlọ Ọgwụ Oncology nke Beijing South Region.

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Ntụaka

1.https://www.cde.org.cn/main/xxgk/listpage/9f9c74c73e0f8f56a8bfbc646055026d

2.发现和开发一流的小分子癌症疗法的领导者 - (ascentage.com)

3.Akwụkwọ: Nchekwa na Ọdịmma nke Olverembatinib (HQP1351) Ejikọtara ya na Lisaftoclax (APG-2575) na ụmụaka na ndị nọ n'afọ iri na ụma nwere ọrịa leukemia Philadelphia Chromosome–Positive Acute Lymphoblastic (R/R Ph ⁺ ALL): Akụkọ Mbụ sitere na Ọmụmụ Nkebi nke 1 (confex.com)