Ngomhlaka-5 Mashi 2025, i-Ascentage Pharma yamemezela ukuthi umuthi wayo, i-olverembatinib, unikezwe i-Breakthrough Therapy Designation (BTD) yi-Center for Drug Evaluation (CDE) ye-China's National Medical Products Administration (NMPA), ngokuhlanganiswa ne-chemotherapy enamandla aphansi ekwelashweni kokuqala kweziguli ezisanda kutholakala ezine-Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL).
Lokhu kuphawula i-BTD yesithathu enikezwe i-olverembatinib eShayina, kanti i-BTD yokuqala enikezwe ngoMashi 2021, yokwelapha iziguli ezine-chronic-phase chronic myeloid leukemia (CML-CP) engazweli futhi/noma engazweli ama-tyrosine kinase inhibitors (TKIs) esizukulwaneni sokuqala nesesibili; kanye ne-BTD yesibili enikezwe ngoJuni 2023, yokwelapha iziguli ezine-succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST) ezazithole ukwelashwa komugqa wokuqala.
Kumenyezelwe eMhlanganweni Waminyaka Yonke Wama-66 we-American Society of Hematology (ASH) Safety and Efficacy of Olverembatinib (HQP1351) Kuhlanganiswe neLisaftoclax (APG-2575) ezinganeni nasebancane abane-Relapsed/Refractory Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia (R/R Ph ALL): Umbiko Wokuqala Ovela Esifundweni Sesigaba 1.
I-Olverembatinib, i-TKI entsha yesizukulwane sesithathu, ibekezelelwa kahle futhi inomsebenzi oqinile futhi ohlala isikhathi eside wokulwa ne-aleukemic kuma-pts ane-CP-CML elashwe kakhulu kusengaphambili ene-T315I mutation noma engenayo. I-lisaftoclax yocwaningo, i-BCL-2 inhibitor entsha, ibonise izinzuzo zezokwelapha zokulwa nomdlavuza kuma-pts ane-bloancies eminingi ye-hematologic. Njengamanje, azikho izinketho zokwelapha ezisebenzayo ezitholakalayo kuma-pts ezingane ane-R/R Ph+ ALL. Lolu cwaningo lwenzelwe ukuhlola ukuphepha, ukusebenza kahle, kanye nephrofayili ye-pharmacokinetic (PK) ye-olverembatinib yodwa noma ehlanganiswe ne-lisaftoclax ezinganeni nasebancane abane-R/R Ph ALL.+
Lolu kwakuwucwaningo lwesigaba 1b oluvulekile (NCT05495035) olubhalise izingane nentsha eneminyaka engaphansi kwengu-18 ene-R/R Ph ALL emelana noma engabekezeleli okungenani i-1 tyrosine kinase inhibitor (TKI) (ukusetshenziswa kwangaphambili kwama-TKI kwakungacatshangwa uma ama-pts ayenokuguqulwa kwe-T315I). Ama-Pts kwakudingeka abe nesilinganiso sesimo sokusebenza esanele se-Karnofsky/Lansky kanye nokusebenza kwezitho zomzimba. Ama-Pts anezimpawu zesifo sesimiso sezinzwa noma ukopha okukhulu, okwakungahlobene ne-PhaLL, ayengafakwanga. I-Olverembatinib yanikezwa ngomlomo ku-40 mg yesilinganiso esilinganayo sabantu abadala (AED) njalo ngemva kwamasonto ama-2 (Izinsuku [D] 1-14), kulandelwe umthamo ofanayo we-olverembatinib kanye ne-lisaftoclax kumthamo onikeziwe ongu-200/400/600 mg (AED) nsuku zonke (QD) ku-D13-42 (kwakudingeka ukwanda komthamo wezinsuku ezi-3 kusuka ku-D13-15). I-Dexamethasone 6 mg/m++ 2/ngosuku yanikezwa ngomlomo i-QD kusukela ku-D15-42. Amaphuzu okugcina ayinhloko ahlanganisa ukuhlolwa kokuphepha, izinga lokuphendula eliphelele (i-ORR), izinga lokungalungi kwesifo esisele esilinganisekayo (i-MRD), kanye nezici ze-PK ze-olverembatinib yodwa/ngokuhlanganiswa ne-lisaftoclax.
Kusukela ngoSepthemba 2022 kuya kuJuni 2024, kwabhaliswa ama-pts ayi-10. Ubudala obumaphakathi (bebanga) babuyiminyaka eyi-13.0 (11-15), kanti ama-pts ayi-6 ayengabesilisa. Isisindo somzimba esimaphakathi (bebanga) sasingu-49.85 (35.9-86.0) kg. Ama-pts ayisishiyagalolunye (90.0%) aveze umbhalo we-p190 kanti i-pt eyi-1 (10.0%) aveze umbhalo we-p210. Ama-pts amathathu ayenezinguquko ze-BCR-ABL1 [2, T315I; 1, F317L (c.951C>A)] ekuqaleni. Ngemva kokuba i-pt eli-1 liyeke ukuhlolwa ngenxa yokuquleka ku-D1 ye-Course 1 (C1D1), ama-pts ayi-9 afanelekile afakiwe kumodeli yokwenyuka komthamo we-3+3 (n = 6, R/R; n = 3, okungabekezeleli): ama-pts ama-3 ku-Arm ngayinye (A, B, kanye no-C) emazingeni omthamo we-lisaftoclax angu-200, 400, kanye no-600 mg (AED), ngokulandelana. Lawa ma-pts aqede izinsuku ezingama-42 zokwelashwa futhi ahlolwa amaphuzu okugcina ayinhloko. Ama-pts ayisithupha kwangu-10 abhekane nezinga ≥ 3 lezehlakalo ezimbi zokwelashwa kwe-hematologic, okuhlanganisa i-anemia (3/10), i-neutropenia (7/10), kanye ne-thrombocytopenia (3/10); i-pt eli-1 landa i-alanine aminotransferase yebanga lesi-3 okwaholela ekuyekeni kokwelashwa, kanti i-pt eli-1 laquleka ku-C1D1 (owayeka ukuhlolwa). Phakathi kwama-pts ayi-6 ahlolwa ngezimpendulo zesimo, i-ORR (ukukhululwa okuphelele [CR] + CR ngokululama kokubala okungaphelele), impendulo engaphelele, kanye namazinga okuphendula angekho, ngokulandelana, ama-2 (33.3%), ama-2 (33.3%), kanye nama-2 (33.3%) ekupheleni kwe-olverembatinib monotherapy (EOM) kanye nama-5 (83.3%), ama-0, kanye nama-1 (16.7%) ekupheleni kwenkambo yokuhlanganiswa kwe-olverembatinib kanye ne-lisaftoclax (EOC). Ama-pts amahlanu kwangu-7 ahlolwayo athole ukungalungi kwe-MRD, okukuwo elilodwa kwakungu-EOM kanye nama-4 ku-EOC. Ukuhlaziywa kokuqala kwe-PK kwembule izici ezifanayo ze-PK kanye nokuvezwa okufanayo phakathi kwezingane kanye nabantu abadala be-olverembatinib kanye ne-lisaftoclax. Akukho ukuqongelela okuphawulekayo ngemva kwemithamo eminingi, futhi akukho ukusebenzisana kwezidakamizwa nezidakamizwa okubonwe phakathi kwe-olverembatinib kanye ne-lisaftoclax.
Le mininingwane yokuqala ikhombisile ukuthi i-olverembatinib ngokuhlanganiswa ne-lisaftoclax ibonakala iyindlela ephephile nephumelelayo ezigulini ezine-R/R Ph ALL. Le ndlela iholele emazingeni athembisayo e-CR ngaphandle kwe-chemotherapy enamandla noma i-immunotherapy. Ucwaningo okwamanje lusesigabeni sokwandiswa komthamo.
Njengamanje, kusenezivivinyo eziningi zemitholampilo zobuchwepheshe obusha bokulwa nomdlavuza eShayina ezifuna iziguli. Ukubonisana ngemithi emisha kanye nobuchwepheshe, ungaxhumana noMnyango Wezizwe Ngezizwe Wesibhedlela iBeijing South Region Oncology.
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Izinkomba
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)
Isikhathi sokuthunyelwe: Mashi-12-2025