Tsoom Fwv Teb Chaws Asmeskas FDA Tso Cai Siv Novartis STAMP Tus Tuav Rau Tshuaj Asciminib 2 Kev Sib Tw Yeeb Tshuaj!

Novartis tsis ntev los no tshaj tawm tias Asmeskas Chaw Tswj Xyuas Khoom Noj thiab Tshuaj (FDA) tau tso cai rau cov tshuaj anticancer tshuaj asciminib (ABL001) nrog ob yam kev sib cais tshuaj (BTD): (1) Rau kev kho mob, tsawg kawg yog ob zaug tau txais Tyrosine kinase inhibitor ( TKI) kev kho mob, Philadelphia chromosome-zoo mob myelogenous mob ntshav dawb (Ph + CML-CP) cov neeg mob laus; (2) rau kev kho mob Ph + CML-CP cov neeg laus laus nrog T315I hloov pauv.

Txawm hais tias kev kho mob ntawm tus mob myelogenous leukemia (CML) tau ua tiav tau zoo nyob rau ntau xyoo dhau los, qee cov neeg mob uas tau kho tau muaj teeb meem ua tiav cov hom phiaj kho vim muaj tshuaj thiab tsis raug txais. Muaj ob peb hom kev kho mob uas tseem tshuav, cov neeg mob nyob tom qab saib xyuas mob yuav muaj qhov pheej hmoo mob zuj zus.

Asciminib yog STAMP inhibitor, uas yav dhau los tau tso cai ceev ntawm Kev khiav ceev (FTD) los ntawm Asmeskas FDA. Cov tshuaj yog ib cov tshuaj uas tshwj xeeb lub hom phiaj myristoyl hnab tshos (STAMP) ntawm BCR-ABL1 protein, uas xauv BCR-ABL1 rau hauv kev ua kom tsis haum. Cov tshuaj sib tw uas tam sim no nyob rau hauv kev ua lag luam yog ua ke nrog ATP khi qhov chaw ntawm BCR-ABL1 protein. Asciminib ua los ntawm kev coj ntawm lwm tus kinase, ABL myristoyl hnab tshos.

Raws li STAMP inhibitor, asciminib tuaj yeem kov yeej kev hloov pauv hauv ATP qhov chaw khi ntawm BCR-ABL1, uas yuav pab daws TKI tsis kam rau kev kho tom qab CML thiab yuav daws cov phiaj xwm kev ua haujlwm, thiaj li txhim kho kev kwv yees ntawm cov neeg mob. Tam sim no, Novartis tab tom sim ua ntau qhov kev soj ntsuam los soj ntsuam asciminib rau cov neeg mob CML uas tau txais kev kho mob ntau yam, nrog rau lwm cov TKI rau kev kho cov neeg mob CML tshiab.

FDA tau tso cai rau asciminib BTD raws li: (1) Cov txiaj ntsig ntawm Theem III ASCEMBL txoj kev kawm, uas tau ua nyob rau cov neeg mob laus uas muaj Ph + CML-CP uas tiv taus lossis tsis nkag siab txog tsawg kawg 2 TKI. Asciminib thiab Bosulif (bosutinib, Bosu Tinib, Pfizer cov khoom lag luam) tau muab sib piv; (2) cov txiaj ntsig ntawm ntu Kuv kawm, txoj kev tshawb fawb c Ph + CML cov neeg mob, qee tus nqa tus T315I hloov mus.

Cov txiaj ntsig tau los ntawm ob qhov kev tshawb fawb no tau tshaj tawm ntawm 2020 American Society of Hematology (ASH) lub rooj sib tham txhua xyoo. Novartis npaj yuav xa cov ntawv thov kev lag luam rau asciminib hauv thawj ib nrab ntawm 2021, txhawm rau tshuaj xyuas nyob rau hauv FDA Oncology Center ntawm Excellence real-time oncology txheeb xyuas qhov project.

Asciminib tshuaj qauv (duab qhov chaw: medchemexpress.cn)

Xyoo tsis ntev los no, kev kho mob ntawm CML tau ua tiav. Cov kws kho mob tuaj yeem xaiv nrog ob peb TKI thaum kho Ph + CML cov neeg mob, suav nrog Novartis's Gleevec (Gleevec, imatinib, imatinib) thiab Tasigna (nilotinib, Nilotinib). Feem ntau ntawm cov neeg mob tau txais kev kho mob tsis tseem ciaj sia tom qab 10 xyoo, tab sis lawv tseem muaj kev pheej hmoo ntawm kev mob tshwm sim.

Txawm hais tias cov neeg mob uas tiv taus thaum pib kho mob tuaj yeem hloov mus rau lwm tus TKI (piv txwv li, ua ntu zus TKI txoj kev kho), ntau txoj kev kho mob tau pom zoo rau tib hom ATP los ua ke rau ntawm ABL1 kinase. Qhov sib thooj ntawm cov kev kho no txhais tau hais tias kev hloov pauv nyob hauv ib cheeb tsam ntawm kinase tuaj yeem hloov ntau yam tshuaj uas tsis muaj txiaj ntsig. Hauv lwm lo lus, kev kho mob TKI uas muaj tshwm sim tuaj yeem cuam tshuam nrog kev tiv thaiv yeeb tshuaj ntau ntxiv thiab kev nkag tsis tau.

Kev kawm Ntu 3 ASCEMBL raug ua nyob rau hauv Ph + CML-CP cov neeg mob uas tiv taus lossis tsis nkag siab txog tsawg kawg ob TKI. Hauv txoj kev tshawb no, 233 cov neeg mob tau txais kev pheej hmoo kom tau txais asciminib (40 mg ob zaug ib hnub, n=157) lossis Bosulif (500 mg ib hnub ib zaug, n=76).

Cov ntaub ntawv tau qhia tias qhov kev tshawb nrhiav tau mus txog qhov kawg: thaum 24 lub lim tiam ntawm kev kho mob, piv nrog Bosulif pawg, qhov loj cov lus teb molecular (MMR) hauv pawg asciminib yuav luag ob npaug (25.5% vs 13.2%; ob txhais caj npab p=0.029). Tsis tas li ntawd, ntawm 24 lub lim tiam ntawm kev kho mob, qhov ua tiav cov lus teb cytogenetic tau ntau dua nyob rau hauv pawg asciminib piv nrog pawg Bosulif (CCyR: 40.8% vs 24.2%), thiab qhov sib sib zog nqus cov lus teb molecular (DMR) tau siab dua: 10.8% hauv pawg asciminib, 8.9% ntawm cov neeg mob ua tiav MR4 thiab MR4.5, piv nrog 5.3% thiab 1.3% hauv pawg Bosulif.

Qhov tshwm sim ntawm qib 3 qhov xwm txheej tsis zoo (AE) hauv pawg asciminib thiab pawg Bosulif yog 50.6% thiab 60.5%, ua ntu zus. Hauv pawg asciminib, qhov feem ntawm cov neeg mob uas tsis kho vim yog cov kev tshwm sim tsis zoo yog 5.8%, piv nrog 21.1% hauv pawg Bosulif. Ib yam li ntawd, qhov nquag tshwm sim ntawm qhov xwm txheej tsis zoo uas yuav tsum muaj kev cuam tshuam cov koob tshuaj thiab / lossis kev hloov kho koob tshuaj hauv pawg asciminib yog qis dua Bosulif (37.8% vs 60.5%). Thaum kawg ntawm ASH cov ntaub ntawv lub rooj sib tham txhua xyoo, qhov feem ntau ntawm cov neeg mob hauv pawg asciminib piv nrog Bosulif pawg tseem tseem tau txais kev kho mob (61.8% vs 30.3%).

Cov kev tshwm sim tsis zoo tshaj plaws ntawm qib ≥3 (tshwm sim> 10%) hauv pawg asciminib yog thrombocytopenia (17.3%) thiab neutropenia (14.7%), thaum pab pawg Bosulif raug nce alanine aminotransferase (ALT) (14.5%), neutropenia (11.8%) thiab zawv plab (10.5%). Ob tus neeg mob (1.3%) hauv cov pawg asciminib (ischemic stroke thiab arterial embolism) tuag; hauv pab pawg neeg Bosulif, ib (1.3%) tus neeg mob (hauv septic shock) tuag. Cov kev tshwm sim tsis zoo tshaj plaws (txhua qib; ≥20%): thrombocytopenia (28.8%) thiab neutropenia (21.8%) hauv pawg asciminib, raws plab (71.1%) thiab xeev siab (46.1%) hauv pab pawg Bosulif, Txhawb siab ALT (27.6) %), ntuav (26.3%), tawm pob ntawm daim tawv nqaij (23.7%), nce aspartate aminotransferase (21.1%), neutropenia (21.1%) thiab thrombocytopenia (18.4%).