Musi wa5 Kurume, 2025, Ascentage Pharma yakazivisa kuti mushonga wayo, olverembatinib, wakapihwa Breakthrough Therapy Designation (BTD) neCenter for Drug Evaluation (CDE) yeChina's National Medical Products Administration (NMPA), nekuda kwekusanganiswa ne low-intensity chemotherapy pakurapa varwere vachangobva kuongororwa vane Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL).
Uyu ndiwo mushonga wechitatu weBTD wakapihwa olverembatinib muChina, wekutanga wakapihwa munaKurume 2021, wekurapa varwere vane chronic-phase chronic myeloid leukemia (CML-CP) inodzivirira uye/kana isingatsungirire tyrosine kinase inhibitors (TKIs) yechizvarwa chekutanga nechechipiri; uye wechipiri wakapihwa munaChikumi 2023, wekurapa varwere vane succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST) avo vakagamuchira mushonga wekutanga.
Zvakaziviswa paMusangano weGore negore wechi66 weAmerican Society of Hematology (ASH) Kuchengetedzwa uye Kushanda kweOlverembatinib (HQP1351) Yakasanganiswa neLisaftoclax (APG-2575) muVana neVachiri Kuyaruka vane Relapsed/Refractory Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia (R/R Ph ALL): Mushumo wekutanga kubva kuChidzidzo chePase 1.
Olverembatinib, mushonga mutsva wechizvarwa chechitatu weTKI, unoshivirira zvakanaka uye une simba uye unogara kwenguva refu mukurapa kweutachiona hwemabhakitiriya ane CP-CML yakamborapwa kare ine kana isina T315I mutation. Investigational lisaftoclax, mushonga mutsva weBCL-2 inhibitor, waratidza mabhenefiti ekurapa ekudzivirira bundu mukurapa kweutachiona hwemabhakitiriya akawanda eropa. Parizvino, hapana nzira dzekurapa dzinoshanda dziripo dzekurapa kwevana vane R/R Ph+ ALL. Chidzidzo ichi chakagadzirirwa kuongorora kuchengetedzeka, kushanda, uye pharmacokinetic (PK) ye olverembatinib chete kana kusanganiswa ne lisaftoclax muvana nevechiri kuyaruka vane R/R Ph ALL.+
Ichi chaive chidzidzo chechikamu chekutanga chebvunzo (NCT05495035) chakaratidza vana nevachiri kuyaruka vane makore ari pasi pe18 vane R/R Ph ALL vasingatsungirire kana vasingatsungirire mushonga weTyrosine Kinase Inhibitor (TKI) (kushandiswa kweTKIs kare hakuna kufungwa nezvako kana mishonga iyi yaive neT315I mutation). Mishonga iyi yaifanirwa kunge iine Karnofsky/Lansky performance status score yakakwana uye mashandiro enhengo. Mishonga iyi yaive nezviratidzo zve central nervous system disorders kana kubuda ropa zvakanyanya, izvo zvaive zvisina chekuita nePhaLL, hazvina kutorwa. Olverembatinib yakapihwa nemuromo pa40 mg yemunhu mukuru (AED) mazuva ese kwemavhiki maviri (Mazuva [D] 1-14), ichiteverwa nedosi imwechete yeolverembatinib pamwe chete nelisaftoclax padosi yakapihwa ye200/400/600 mg (AED) zuva nezuva (QD) paD13-42 (kuwedzera kwedosi kwemazuva matatu kubva kuD13-15 kwaidiwa). Dexamethasone 6 mg/m++ 2/zuva yakapihwa nemuromo QD kubva kuD15-42. Magumo ekutanga aisanganisira kuongororwa kwekuchengetedza, chiyero chemhinduro yose (ORR), chiyero chekusagadzikana kwechirwere chinoyerwa (MRD), uye hunhu hwePK hwe olverembatinib chete/pamwe chete ne lisaftoclax.
Kubva munaGunyana 2022 kusvika muna Chikumi 2024, vanhu gumi vakanyoreswa. Zera repakati (renji) raive makore 13.0 (11-15), uye vanhurume 6 pts vaive. Huremu hwemuviri (renji) hwaive 49.85 (35.9-86.0) kg. Mapfumbamwe (90.0%) pts akaratidza p190 transcript uye 1 pt (10.0%) akaratidza p210 transcript. Matatu pts aive neBCR-ABL1 mutations [2, T315I; 1, F317L (c.951C>A)] pakutanga. Mushure mekunge pt imwe yamiswa kubva mukuyedzwa nekuda kwekubata paD1 yeCourse 1 (C1D1), pt 9 dzakakodzera dzakaverengerwa mumuenzaniso we3+3 dose escalation (n = 6, R/R; n = 3, isingashiviriri): pt 3 muArm yega yega (A, B, naC) pamazinga e lisaftoclax dose akapihwa e200, 400, uye 600 mg (AED), zvichiteerana. pt idzi dzakapedza mazuva 42 ekurapwa uye dzakaongororwa kuti dzionekwe kuti ndeapi mapoinzi ekutanga. Nhanhatu papt 10 dzakasangana nezviitiko zvakaipa zvekurapa kweropa zvegiredhi ≥ 3, zvinosanganisira anemia (3/10), neutropenia (7/10), uye thrombocytopenia (3/10); pt imwe chete yaive nekuwedzera kwealanine aminotransferase yegiredhi 3 zvichikonzera kuregera kurapwa, uye pt imwe chete yaive nekubata paC1D1 (iyo yakarega kuyedzwa). Pakati pemapfundo matanhatu anoongororwa pamhinduro dzemuviri, ORR (kuregeredzwa kwakazara [CR] + CR ine kupora kwehuwandu husina kukwana), mhinduro isina chikamu, uye pasina huwandu hwemhinduro, zvichiteerana, 2 (33.3%), 2 (33.3%), uye 2 (33.3%) pakupera kwe olverembatinib monotherapy (EOM) uye 5 (83.3%), 0, uye 1 (16.7%) pakupera kwe olverembatinib ne lisaftoclax combination course (EOC). Mapfundo mashanu pa7 anoongororwa akawana MRD negativity, iyo imwe yaive pa EOM uye 4 pa EOC. Ongororo yekutanga ye PK yakaratidza hunhu hwakafanana hwe PK uye kuratidzwa kwakafanana pakati pevana nevakuru ve olverembatinib ne lisaftoclax. Pakanga pasina kuunganidzwa kwakakosha mushure mekushandisa mishonga yakawanda, uye hapana kusangana kwemishonga nezvinodhaka kwakaonekwa pakati pe olverembatinib ne lisaftoclax.
Ruzivo rwekutanga urwu rwakaratidza kuti olverembatinib pamwe chete nelisaftoclax inoita seyakachengeteka uye inoshanda muvarwere vane R/R Ph ALL. Iyi nzira yakaguma nekuwedzera kweCR pasina chemotherapy yakanyanya kana immunotherapy. Chidzidzo ichi chiri muchikamu chekuwedzera dose.
Parizvino, kuchine miedzo yakawanda yekiriniki yehunyanzvi hutsva hwekurwisa gomarara muChina huri kutsvaga varwere. Kana muchida kubvunzana nezvemishonga mitsva netekinoroji, munogona kubata Dhipatimendi reBeijing South Region Oncology Hospital International.
Nhamba yefoni: 4008803716
Email：myimmnet@163.com
Mareferensi
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)
Nguva yekutumira: Kurume-12-2025