Ma Malaki 5, 2025, ua hoʻolaha ʻo Ascentage Pharma ua hāʻawi ʻia kāna lāʻau lapaʻau, ʻo olverembatinib, i kahi Breakthrough Therapy Designation (BTD) e ke Center for Drug Evaluation (CDE) o ka National Medical Products Administration (NMPA) o Kina, no ka hui pū ʻana me ka chemotherapy haʻahaʻa no ka mālama mua ʻana i nā maʻi i ʻike hou ʻia me ka Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL).
ʻO kēia ka BTD ʻekolu i hāʻawi ʻia i ka olverembatinib ma Kina, me ka BTD mua i hāʻawi ʻia i Malaki 2021, no ka mālama ʻana i nā maʻi me ka chronic-phase chronic myeloid leukemia (CML-CP) kūʻē a/a i ʻole intolerant i nā tyrosine kinase inhibitors (TKIs) hanauna mua a me ka lua; a me ka lua o ka BTD i hāʻawi ʻia i Iune 2023, no ka mālama ʻana i nā maʻi me ka succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST) i loaʻa ka lāʻau lapaʻau laina mua.
Ua hoʻolaha ʻia ma ka Hālāwai Makahiki 66 o ka American Society of Hematology (ASH) Palekana a me ka Pono o Olverembatinib (HQP1351) i hui pū ʻia me Lisaftoclax (APG-2575) i nā keiki a me nā ʻōpio me ka Relapsed/Refractory Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia (R/R Ph ALL): Hōʻike mua mai kahi Haʻawina Phase 1.
ʻO Olverembatinib, kahi TKI hanauna ʻekolu hou, ua ʻae maikaʻi ʻia a hoʻokō i ka hana antileukemic ikaika a paʻa i nā pts me ka CP-CML i mālama mua ʻia me ka ʻole o ka mutation T315I. Ua hōʻike ʻo lisaftoclax noiʻi, kahi mea hoʻopaʻa BCL-2 hou, i nā pono antitumor lapaʻau i nā pts me nā maʻi hematologic he nui. I kēia manawa, ʻaʻohe koho lapaʻau kūpono i loaʻa no nā pts pediatric me R/R Ph+ ALL. Ua hoʻolālā ʻia kēia haʻawina e ʻimi i ka palekana, ka pono, a me ka pharmacokinetic (PK) profile o olverembatinib wale nō a i hui pū ʻia me lisaftoclax i nā keiki a me nā ʻōpio me R/R Ph ALL.+
He haʻawina hāmama kēia, pae 1b (NCT05495035) i hoʻopaʻa inoa i nā keiki a me nā ʻōpio i piha i ka makahiki <18 me ka pale ʻana o R/R Ph ALL a i ʻole ka hoʻomanawanui ʻole i ka liʻiliʻi he 1 tyrosine kinase inhibitor (TKI) (ʻaʻole i noʻonoʻo ʻia ka hoʻohana mua ʻana o TKI inā loaʻa i nā pts ka hoʻololi ʻana o T315I). Pono nā Pts e loaʻa i ka helu kūlana hana Karnofsky/Lansky kūpono a me ka hana o ke kino. Ua kāpae ʻia nā Pts me nā maʻi ʻōnaehana nerve waena a i ʻole ke kahe koko nui, ʻaʻole pili i ka PhALL. Ua lawelawe waha ʻia ʻo Olverembatinib ma ka 40 mg like me ka pākeke (AED) i kēlā me kēia lā ʻē aʻe no 2 mau pule (Nā lā [D] 1-14), a ukali ʻia e ka nui like o olverembatinib i hui pū ʻia me lisaftoclax ma kahi mahele i hāʻawi ʻia o 200/400/600 mg (AED) i kēlā me kēia lā (QD) ma D13-42 (pono ka hoʻonui ʻana i ka mahele 3 lā mai D13-15). Ua hāʻawi waha ʻia ʻo Dexamethasone 6 mg/m++ 2/lā QD mai D15-42. ʻO nā kiko hopena mua e pili ana i nā loiloi palekana, ka helu pane holoʻokoʻa (ORR), ka helu negativity o ka maʻi koena hiki ke ana ʻia (MRD), a me nā ʻano PK o olverembatinib wale nō/i hui pū ʻia me lisaftoclax.
Mai Kepakemapa 2022 a i Iune 2024, ua kākau inoa ʻia he 10 mau pts. ʻO ka makahiki waena (pae) he 13.0 (11-15) mau makahiki, a he 6 mau pts he kāne. ʻO ke kaumaha o ke kino waena (pae) he 49.85 (35.9-86.0) kg. ʻEiwa (90.0%) pts i hōʻike i ka palapala p190 a 1 pt (10.0%) i hōʻike i ka palapala p210. ʻEkolu mau pts i loaʻa nā hoʻololi BCR-ABL1 [2, T315I; 1, F317L (c.951C>A)] ma ka baseline. Ma hope o ka hoʻopau ʻia ʻana o 1 pt mai ka hoʻokolohua ma muli o ka hopu ʻana ma D1 o ka Papa 1 (C1D1), ua hoʻokomo ʻia he 9 mau pts kūpono i loko o ke kumu hoʻohālikelike hoʻonui 3+3 dose (n = 6, R/R; n = 3, intolerant): 3 pts ma kēlā me kēia Arm (A, B, a me C) ma nā pae dose lisaftoclax i hāʻawi ʻia he 200, 400, a me 600 mg (AED), kēlā me kēia. Ua hoʻopau kēia mau pts i 42 mau lā o ka mālama ʻana a ua loiloi ʻia no nā kiko hopena mua. ʻEono o 10 pts i ʻike i nā hanana ʻino hematologic grade ≥ 3, me ka anemia (3/10), neutropenia (7/10), a me ka thrombocytopenia (3/10); Loaʻa i ka 1 pt ka piʻi ʻana o ka alanine aminotransferase grade 3 e alakaʻi ana i ka hoʻopau ʻana i ka mālama ʻana, a loaʻa i ka 1 pt kahi hopu ma C1D1 (nāna i hoʻopau i ka hoʻokolohua). Ma waena o 6 mau pts i hiki ke loiloi ʻia no nā pane morphologic, ʻo ORR (hoʻomaha piha [CR] + CR me ka hoʻōla helu piha ʻole), pane hapa, a ʻaʻohe pane pane, ʻo ia hoʻi, 2 (33.3%), 2 (33.3%), a me 2 (33.3%) ma ka hopena o ka olverembatinib monotherapy (EOM) a me 5 (83.3%), 0, a me 1 (16.7%) ma ka hopena o ka hui pū ʻana o olverembatinib a me lisaftoclax (EOC). ʻElima o 7 mau pts i hiki ke loiloi ʻia i loaʻa ka MRD negativity, ʻo 1 ma EOM a me 4 ma EOC. Ua hōʻike nā loiloi PK mua i nā ʻano PK like a me ka hōʻike like ʻana ma waena o nā heluna pediatric a me nā pākeke no olverembatinib a me lisaftoclax. ʻAʻohe hōʻiliʻili koʻikoʻi ma hope o nā lāʻau he nui, a ʻaʻohe pilina lāʻau-lāʻau i ʻike ʻia ma waena o olverembatinib a me lisaftoclax.
Ua hōʻike kēia ʻikepili mua e like me ka hui pū ʻana o ka olverembatinib me ka lisaftoclax he regimen palekana a maikaʻi hoʻi i nā poʻe maʻi me R/R Ph ALL. Ua hopena kēia regimen i nā helu CR hoʻohiki me ka ʻole o ka chemotherapy ikaika a i ʻole immunotherapy. Aia ke aʻo ʻana i kēia manawa ma ka pae hoʻonui dosis.
I kēia manawa, nui nā hoʻokolohua lapaʻau o nā ʻenehana anti-cancer hou ma Kina e ʻimi nei i nā maʻi. I ke kūkākūkā ʻana i nā lāʻau lapaʻau a me nā ʻenehana hou, hiki iā ʻoe ke hoʻokaʻaʻike aku i ka Beijing South Region Oncology Hospital International Department.
Helu Kelepona：4008803716
Email：myimmnet@163.com
Nā Kuhikuhi
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)
Ka manawa hoʻouna: Malaki-12-2025