Ngomhla wesi-5 kweyoKwindla, ngo-2025, i-Ascentage Pharma yabhengeza ukuba iyeza layo, i-olverembatinib, linikwe iBreakthrough Therapy Designation (BTD) yiZiko loVavanyo lwaMayeza (CDE) le-China's National Medical Products Administration (NMPA), ukuze lidityaniswe ne-chemotherapy engaphantsi kwamandla aphantsi kunyango lokuqala lwezigulane ezisandula ukuxilongwa ezine-Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL).
Oku kubonisa i-BTD yesithathu enikwe i-olverembatinib eTshayina, kunye ne-BTD yokuqala enikwe ngoMatshi 2021, yokunyanga izigulane ezine-chronic-phase chronic myeloid leukemia (CML-CP) enganyamezelaniyo kunye/okanye enganyamezelaniyo ne-tyrosine kinase inhibitors (TKIs) yesizukulwana sokuqala nesesibini; kunye ne-BTD yesibini enikwe ngoJuni 2023, yokunyanga izigulane ezine-succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST) ezifumene unyango lokuqala.
Ibhengezwe kwiNtlanganiso yoNyaka yama-66 ye-American Society of Hematology (ASH) Safety and Efficacy of Olverembatinib (HQP1351) Idityaniswe neLisaftoclax (APG-2575) kubantwana nakwishumi elivisayo abaneRelapsed/Refractory Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia (R/R Ph ALL): Ingxelo yokuqala evela kwiSifundo seSigaba soku-1.
I-Olverembatinib, isizukulwana sesithathu se-TKI, iyakwazi ukunyamezelwa kakuhle kwaye inomsebenzi onamandla nohlala ixesha elide wokulwa ne-aleukemic kwi-pts ezine-CP-CML enyangiweyo kakhulu ene-T315I mutation okanye engenayo. I-lisaftoclax yophando, i-BCL-2 inhibitor entsha, ibonise iingenelo zonyango zokulwa ne-tumor kwi-pts ezine-hematologic malignancies ezininzi. Okwangoku, akukho ndlela zonyango ezisebenzayo ezikhoyo kwi-pts zabantwana ezine-R/R Ph+ ALL. Olu phononongo lwenzelwe ukuphonononga ukhuseleko, ukusebenza kakuhle, kunye neprofayili ye-pharmacokinetic (PK) ye-olverembatinib yodwa okanye idityaniswe ne-lisaftoclax kubantwana nakubantu abaselula abane-R/R Ph ALL.+
Olu yayiluphando oluvulekileyo, lwesigaba 1b (NCT05495035) olubhalise abantwana kunye nabakwishumi elivisayo abaneminyaka engaphantsi kwe-18 ubudala abane-R/R Ph ALL abamelana okanye abanganyamezelaniyo ubuncinane ne-1 tyrosine kinase inhibitor (TKI) (ukusetyenziswa kwangaphambili kwee-TKIs akuzange kuthathelwe ingqalelo ukuba ii-pts zazinotshintsho lwe-T315I). Ii-Pts zazifuneka ukuba zibe nenqanaba elifanelekileyo lokusebenza kweKarnofsky/Lansky kunye nokusebenza kwamalungu omzimba. Ii-Pts ezineempawu zeengxaki zenkqubo ye-nervous system okanye ukopha okukhulu, ezazinganxulumananga ne-PhaLL, azizange zikhutshwe. I-Olverembatinib yanikwa ngomlomo kwi-40 mg yedosi elinganayo yabantu abadala (AED) yonke imihla kangangeeveki ezi-2 (Iintsuku [D] 1-14), kulandele idosi efanayo ye-olverembatinib kunye ne-lisaftoclax kwidosi emiselweyo ye-200/400/600 mg (AED) imihla ngemihla (QD) kwi-D13-42 (kwakufuneka idosi yeentsuku ezi-3 ukusuka kwi-D13-15). I-Dexamethasone 6 mg/m++ 2/ngosuku inikwe ngomlomo i-QD evela kwi-D15-42. Amanqaku okugqibela aphambili aquka uvavanyo lokhuseleko, izinga lokuphendula ngokubanzi (ORR), izinga lokungavumi ukuphinda kusetyenziswe isifo (MRD), kunye neempawu ze-PK ze-olverembatinib yodwa/ngokudibaniswa ne-lisaftoclax.
Ukususela ngoSeptemba 2022 ukuya kuJuni 2024, kwabhaliswa ii-pts ezili-10. Ubudala obuphakathi (uluhlu) babuyiminyaka eyi-13.0 (11-15), kwaye ii-pts ezi-6 yayiziindoda. Ubunzima bomzimba obuphakathi (uluhlu) babuyi-49.85 (35.9-86.0) kg. Ii-pts ezilithoba (90.0%) zaveza i-p190 transcript kwaye i-1 pt (10.0%) yaveza i-p210 transcript. Ii-pts ezintathu zazine-BCR-ABL1 mutations [2, T315I; 1, F317L (c.951C>A)] ekuqaleni. Emva kokuba i-1 pt iyekiwe kuvavanyo ngenxa yokuxhuzula kwi-D1 yeKhosi 1 (C1D1), ii-pts ezili-9 ezifanelekileyo zafakwa kwimodeli yokunyuka kwedosi ye-3+3 (n = 6, R/R; n = 3, enganyamezelaniyo): ii-pts ezi-3 kwi-Arm nganye (A, B, kunye ne-C) kumanqanaba edosi ye-lisaftoclax anikiweyo angama-200, 400, kunye nama-600 mg (AED), ngokwahlukeneyo. Ezi pts zigqibe iintsuku ezingama-42 zonyango kwaye zavavanywa kwiindawo eziphambili zokugqibela. Iipts ezintandathu kwezili-10 zafumana iziphumo ezimbi zonyango lwe-hematologic lwebanga ≥ 3, kubandakanya i-anemia (3/10), i-neutropenia (7/10), kunye ne-thrombocytopenia (3/10); I-1 pt yayinokwanda kwe-alanine aminotransferase yebanga lesi-3 okwakhokelela ekuyekeni konyango, kwaye i-1 pt yaxhuzula kwi-C1D1 (eyayiyekile uvavanyo). Phakathi kwee-pts ezi-6 ezivavanywayo kwiimpendulo ze-morphologic, i-ORR (ukukhululwa okupheleleyo [CR] + CR kunye nokubuyiswa kokubala okungaphelelanga), impendulo engaphelelanga, kunye namazinga okuphendula, ngokulandelanayo, ezi-2 (33.3%), ezi-2 (33.3%), kunye nezi-2 (33.3%) ekupheleni kwe-olverembatinib monotherapy (EOM) kunye nezi-5 (83.3%), 0, kunye ne-1 (16.7%) ekupheleni kwekhosi yokudibanisa i-olverembatinib kunye ne-lisaftoclax (EOC). Ezintlanu kwezi-7 ezivavanywayo zifumene i-MRD negativity, apho enye yayikwi-EOM kwaye ezi-4 kwi-EOC. Uhlalutyo lokuqala lwe-PK lutyhile iimpawu ezifanayo ze-PK kunye nokuvezwa okufanayo phakathi kwabantwana kunye nabantu abadala kwi-olverembatinib kunye ne-lisaftoclax. Akukho kuqokelelana okubalulekileyo emva kweedosi ezininzi, kwaye akukho nxibelelwano lwamayeza neziyobisi olubonwe phakathi kwe-olverembatinib kunye ne-lisaftoclax.
Olu lwazi lokuqala lubonise ukuba i-olverembatinib kunye ne-lisaftoclax ibonakala iyirejimeni ekhuselekileyo nesebenzayo kwizigulane ezine-R/R Ph ALL. Olu rejimeni lubangele ukuba amazinga e-CR athembiswe ngaphandle kwe-chemotherapy okanye i-immunotherapy enzulu. Olu phononongo okwangoku lukwisigaba sokwandiswa kwedosi.
Okwangoku, kusekho iimvavanyo ezininzi zeklinikhi zobuchwepheshe obutsha bokulwa nomhlaza eTshayina obufuna izigulane. Iingcebiso ngamayeza amatsha kunye nobuchwepheshe, ungaqhagamshelana neSebe leMicimbi yeZibhedlele ze-Oncology zaseBeijing South Region.
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Email：myimmnet@163.com
Iireferensi
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)
Ixesha leposi: Matshi-12-2025