Pa Marichi 5, 2025, Ascentage Pharma idalengeza kuti mankhwala ake, olverembatinib, apatsidwa Breakthrough Therapy Designation (BTD) ndi Center for Drug Evaluation (CDE) ya China's National Medical Products Administration (NMPA), chifukwa chophatikiza ndi chemotherapy yotsika kwambiri pochiza odwala omwe angopezeka kumene ndi Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL).
Izi zikuyimira BTD yachitatu yomwe idaperekedwa ku olverembatinib ku China, ndipo BTD yoyamba idaperekedwa mu Marichi 2021, yochizira odwala omwe ali ndi matenda a chronic-phase chronic myeloid leukemia (CML-CP) osagonja komanso/kapena osagonja ku tyrosine kinase inhibitors (TKIs) ya m'badwo woyamba ndi wachiwiri; ndipo BTD yachiwiri idaperekedwa mu Juni 2023, yochizira odwala omwe ali ndi succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST) omwe adalandira chithandizo choyamba.
Yalengezedwa pa Msonkhano Wapachaka wa 66 wa American Society of Hematology (ASH) Safety and Efficacy of Olverembatinib (HQP1351) Yophatikizidwa ndi Lisaftoclax (APG-2575) mwa Ana ndi Achinyamata omwe ali ndi Relapsed/Refractory Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia (R/R Ph ALL): Lipoti Loyamba kuchokera ku Kafukufuku wa Gawo 1.
Olverembatinib, mtundu watsopano wa TKI wa m'badwo wachitatu, umalekerera bwino ndipo umagwira ntchito yolimbana ndi kutupa kwa minofu m'matenda a mtima omwe ali ndi CP-CML yochiritsidwa kale komanso yopanda kusintha kwa T315I. Lisaftoclax yofufuza, yoletsa BCL-2 yatsopano, yawonetsa ubwino wotsutsana ndi chotupa m'matenda a mtima omwe ali ndi khansa yambiri. Pakadali pano, palibe njira zochizira zogwira mtima zomwe zilipo pa matenda a mtima a ana omwe ali ndi R/R Ph+ ALL. Kafukufukuyu adapangidwa kuti afufuze chitetezo, mphamvu, ndi mbiri ya pharmacokinetic (PK) ya olverembatinib yokha kapena kuphatikiza ndi lisaftoclax mwa ana ndi achinyamata omwe ali ndi R/R Ph ALL.+
Uwu unali kafukufuku wotseguka, wa gawo 1b (NCT05495035) womwe unalembetsa ana ndi achinyamata azaka zosakwana 18 omwe ali ndi R/R Ph ALL omwe salola kapena osalolera mankhwala oletsa tyrosine kinase (TKI) osachepera 1 (kugwiritsa ntchito TKIs kale sikunaganiziridwe ngati ma pts anali ndi kusintha kwa T315I). Ma Pts anafunika kukhala ndi chiŵerengero chokwanira cha momwe Karnofsky/Lansky amagwirira ntchito komanso momwe ziwalo zimagwirira ntchito. Ma Pts omwe ali ndi zizindikiro za matenda a mitsempha yapakati kapena kutuluka magazi kwambiri, omwe sanali okhudzana ndi PhaLL, sanaphatikizidwe. Olverembatinib inaperekedwa pakamwa pa mlingo wofanana ndi wa akuluakulu (AED) tsiku lililonse kwa milungu iwiri (Masiku [D] 1-14), kutsatiridwa ndi mlingo womwewo wa olverembatinib pamodzi ndi lisaftoclax pa mlingo woperekedwa wa 200/400/600 mg (AED) tsiku lililonse (QD) pa D13-42 (kuwonjezeka kwa mlingo wa masiku atatu kuchokera ku D13-15 kunafunika). Dexamethasone 6 mg/m++ 2/tsiku adaperekedwa pakamwa QD kuchokera ku D15-42. Mapeto ake akuluakulu adaphatikizapo kuwunika chitetezo, kuchuluka kwa mayankho onse (ORR), kuchuluka kwa matenda otsalira (MRD) koyipa, ndi mawonekedwe a PK a olverembatinib yokha/mosakanikirana ndi lisaftoclax.
Kuyambira mu Seputembala 2022 mpaka Juni 2024, anthu 10 onse analembetsa. Apakati (zaka) anali ndi zaka 13.0 (11-15), ndipo 6 anali amuna. Kulemera kwapakati (zaka) kunali 49.85 (35.9-86.0) kg. Ma pts asanu ndi anayi (90.0%) anali ndi p190 ndipo 1 pt (10.0%) anali ndi p210. Ma pts atatu anali ndi kusintha kwa BCR-ABL1 [2, T315I; 1, F317L (c.951C>A)] poyambira. Pambuyo poti imodzi itasiya kuyesedwa chifukwa cha khunyu pa D1 ya Course 1 (C1D1), ma pts 9 oyenerera adaphatikizidwa mu chitsanzo cha 3+3 dose escalation (n = 6, R/R; n = 3, osalekerera): ma pts 3 mu Arm iliyonse (A, B, ndi C) pamlingo wa lisaftoclax womwe unaperekedwa wa 200, 400, ndi 600 mg (AED), motsatana. Ma pts awa adamaliza masiku 42 a chithandizo ndipo adawunikidwa kuti awone ngati ali ndi mfundo zazikulu. Ma pts asanu ndi limodzi mwa 10 adakumana ndi zovuta za hematologic ≥ 3, kuphatikizapo kuchepa kwa magazi m'thupi (3/10), neutropenia (7/10), ndi thrombocytopenia (3/10); poti imodzi inali ndi kuwonjezeka kwa alanine aminotransferase ya kalasi 3 zomwe zidapangitsa kuti chithandizocho chisiye, ndipo poti imodzi idakumana ndi khunyu pa C1D1 (yemwe adasiya kuyesedwa). Pakati pa ma pts 6 omwe amayesedwa kuti apeze mayankho a morphologic, ORR (kuchotsera kwathunthu [CR] + CR yokhala ndi kuchira kosakwanira kwa kuwerengera), yankho pang'ono, komanso kuchuluka kwa mayankho osayankhidwa, motsatana, 2 (33.3%), 2 (33.3%), ndi 2 (33.3%) kumapeto kwa olverembatinib monotherapy (EOM) ndi 5 (83.3%), 0, ndi 1 (16.7%) kumapeto kwa olverembatinib ndi lisaftoclax combination course (EOC). Ma pts asanu mwa 7 omwe amayesedwa adapeza MRD negativity, pomwe 1 inali pa EOM ndi 4 pa EOC. Kusanthula koyambirira kwa PK kunawonetsa makhalidwe ofanana a PK ndi kuwonetsedwa kofanana pakati pa ana ndi akuluakulu a olverembatinib ndi lisaftoclax. Panalibe kuchuluka kwakukulu pambuyo pa kuchuluka kwa mankhwala, ndipo palibe kuyanjana kwa mankhwala ndi mankhwala komwe kunawonedwa pakati pa olverembatinib ndi lisaftoclax.
Deta yoyambirira iyi yasonyeza kuti olverembatinib pamodzi ndi lisaftoclax ikuwoneka kuti ndi njira yotetezeka komanso yothandiza kwa odwala omwe ali ndi R/R Ph ALL. Njira imeneyi inapangitsa kuti pakhale kuchuluka kwa CR komwe kungachitike popanda mankhwala amphamvu a chemotherapy kapena immunotherapy. Kafukufukuyu pakadali pano ali mu gawo lokulitsa mlingo.
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.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)
Nthawi yotumizira: Marichi-12-2025