Qinlock, Thawj Qhov Plaub-Tshuaj Yeeb Tshuaj-kinase Tus Raug Txwv, Tau Pom Zoo Rau Kev Lag Luam Hauv Tebchaws Meskas, Thiab Tom Qab ntawd Ding Tshuaj Kho Tau Tshaj Hauv Suav!

Zaiping Pharmaceutical' tus khub Deciphera Pharmaceuticals nyuam qhuav tshaj tawm tias Cov Khoom Noj thiab Tshuaj Noj (FDA) tau pom zoo nws cov khoom siv dav-KIT thiab PDGFRα kinase inhibitor Qinlock (ripretinib) rau kev kho plaub-kab ntawm kev mob siab hnyuv qog nqaij hlav. (GIST). Qinlock yog qhov tsim nyog rau cov neeg mob neeg laus uas yav tas los tau kho nrog 3 lossis ntau dua kinase inhibitors, suav nrog: imatinib, sunitinib, regorafenib. Lub Rau Hli 2019, Zaiding Pharmaceutical tau kos npe pom zoo nrog Deciphera kom tau txais daim ntawv tso cai tshwj xeeb rau kev txhim kho thiab txhawb Qinlock hauv Greater Tuam Tshoj (Tuam Tshoj Mainland, Hong Kong, Macau thiab Taiwan).

Nws yog tsim nyog teev tias Qinlock yog thawj cov tshuaj tshiab raug pom zoo rau kev kho plaub-kab ntawm GIST, uas yog qhov cim tseem ceeb. GIST yog lub qog uas pib tawm hauv lub plab zom mov, thiab feem ntau cov neeg mob uas pib teb rau tsoos tyrosine kinase inhibitors yuav kawg hlav qog vim hloov mus ua lwm yam. Hauv theem III INVICTUS txoj kev tshawb nrhiav, Qinlock qhia tau txais pov thawj kev saib xyuas kev kho mob raws li kev muaj mob tsis muaj kev vam meej (PFS) thiab tag nrho cov kev muaj sia nyob (OS), thiab muaj kev nyab xeeb thiab tiv taus zoo. Cov tshuaj yuav yog plaub GIST muab txoj kev kho mob tshiab tseem ceeb.

Qhov kev pom zoo yog peb lub hlis ua ntej ntawm lub hom phiaj ua hnub. Qinlock hom phiaj ntau yam ntawm KIT thiab PDGFRα kev hloov pauv, uas paub tias yuav tsav GIST. Yav dhau los, FDA tau tso cai Qinlock Kev Tshawb Fawb Kev Tsim Yeeb Tshuaj (BTD), Kev Nkag Mus Kawm Ceev Ceev (FTD), Kev Ntsuas Ua Ntej Kev Ntsuam Xyuas (PRD), thiab tshuaj xyuas cov ntawv thov kev siv tshuaj tshiab (NDA) raws li cov kev soj ntsuam ntawm oncology (RTOR) cov kev sim. Qinlock NDA tseem yog ib feem ntawm Orbis project, ib qho kev pib ua haujlwm ntawm Center for Excellence in Oncology (OCE) ntawm Asmeskas FDA, uas muab lub hauv paus rau kev koom nrog thoob ntiaj teb kev tswj hwm cov koom haum kom ib txhij xa thiab tshuaj xyuas oncology tshuaj.

Richard Pazdur, MD, tus thawj coj ntawm FDA Center for Excellence incology thiab ua yeeb yam tus thawj coj ntawm chaw haujlwm Oncology thiab Kab Mob ntawm FDA Center rau Kev Tshuaj Ntsuam Xyuas thiab Tshawb Fawb, tau hais tias: "Txawm hais tias muaj kev txhim kho hauv kev txhim kho GIST kev kho mob yav dhau los 20 xyoo, suav nrog plaub FDA pom zoo tsom kev kho txoj kev-Imatinib [2002], Sunitinib [2006], Rigofenib [2013], Avapriny [avapritinib, {{6 }}] - tab sis qee tus neeg mob tsis teb rau kev kho Tus mob qog txuas ntxiv mus. Niaj hnub no kev pom zoo muab txoj kev kho mob tshiab rau cov neeg mob uas tau tso pa dhau los ntawm FDA pom zoo GIST kho."

Qinlock' s lub tshuaj kws tshuaj ua kom nquag plias yog ripretinib, uas yog KIT / PDGFRα kinase hloov mus tswj cov tshuaj tiv thaiv kab mob, siv los kho KIT / PDGFR driven-uas tau tsav lub plab zom mov (GIST), cov kab mob mastocytosis (SM), thiab lwm tus mob cancer. Ripretinib tau tsim tshwj xeeb los txhim kho kev kho mob rau cov neeg mob lub plab hnyuv qog los ntawm kev tiv thaiv txoj kev hloov pauv ntau ntawm KIT thiab PDGFRα. ripretinib nplov qhov pib thiab theem ob kev hloov pauv KIT nyob rau hauv exons 9, 11, 13, 14, 17, 18 koom nrog kev mob plab hnyuv qog thiab tus thawj KIT exon 17 pom hauv SM Son D 816 V hloov chaw. Ripretinib tseem inhibits thawj PDGFRα kev hloov pauv hauv exons 12, 14 thiab 18, suav nrog kev mob plab cov leeg ua haujlwm uas cuam tshuam nrog kev hloov pauv hauv exon 18 D 842 V.

Lub Rau Hli 2019, Zaiding Pharmaceutical tau txais daim ntawv tso cai tshwj xeeb los ntawm Deciphera los tsim kho thiab txhawb nqa ripretinib hauv Greater Tuam Tshoj (Tuam Tshoj Mainland, Hong Kong, Macau thiab Taiwan). Raws li qhov kev pom zoo, Deciphera yuav tau txais nyiaj ua ntej ntawm $ 20 lab thiab tsim nyog tau txais txog $ 185 lab hauv kev tsim kho thiab kev lag luam cov nyiaj tseem ceeb. Ib qho ntxiv, Zai Ding Cov Khoom Siv Tshuaj yuav tau them tus nqi Deciphera rau cov nqi raws li ripretinib' s txhua xyoo muag muag hauv Suav Loj.

Qhov kev pom zoo no yog ua raws kev ntsuas ntawm cov txiaj ntsig ntawm cov ntaub ntawv tseem ceeb theem III INVICTUS (NCT 03353753) kawm txog Qinlock kev kho plaub ntawm GIST, thiab cov ntaub ntawv kev nyab xeeb ntawm INVICTUS thiab theem I kev kawm. INVICTUS yog ib qho kev tsim kho (2: 1), ob chav dig muag, qhov chaw kawm tshuaj uas tau tso npe 1 2 9 cov neeg mob uas yav tas los tau txais ntau yam kev kho mob (suav nrog tsawg kawg imatinib, sunitinib, thiab regofenib) Cov neeg mob uas muaj GIST siab tau soj ntsuam kev ua tau zoo thiab kev nyab xeeb ntawm Qinlock tus txheeb ze rau cov placebo.

Cov txiaj ntsig tau tshaj tawm thaum Lub Yim Hli 2019 pom tias txoj kev tshawb no tau mus txog qhov kawg: piv rau cov placebo, qhov kev vam meej-tsis ciaj sia tau ntev ntev hauv Qinlock pab pawg kho mob (nruab nrab PFS: 6. {{3} } lub hlis vs {{{4}}. 0 lub hlis), kev pheej hmoo ntawm kab mob kev loj hlob lossis kev tuag tseem ceeb txo los ntawm 85% (HR=0. 15, p< 0.="" {0001).="" hais="" txog="" kev="" ua="" tiav="" qhov="" kawg="" ntawm="" tag="" nrho="" cov="" kev="" ciaj="" sia="" (os),="" qinlock="" pab="" pawg="" kho="" mob="" tau="" ntev="" dua="" cov="" pab="" pawg="" placebo="" (qhov="" nruab="" nrab="" os:="" {{4}}="" 5.="" 1="" lub="" hlis="" vs="" 6.="" {{1="" 4}}="" lub="" hlis),="" thiab="" kev="" pheej="" hmoo="" ntawm="" kev="" tuag="" tau="" txo="" los="" ntawm="" 6="" 4%="" (hr="0." 36,="" nominal="" p="0." {{="" 19}});="" nws="" yog="" tsim="" nyog="" sau="" cia="" tias="" os="" cov="" ntaub="" ntawv="" ntawm="" cov="" placebo="" pab="" pawg="" muaj="" cov="" ntaub="" ntawv="" ntawm="" cov="" neeg="" mob="" uas="" tig="" mus="" rau="" qinlock="" tom="" qab="" cov="" placebo="" kev="" kho="" mob="" tau="" ua="" tiav.="" hauv="" kev="" hais="" txog="" tag="" nrho="" cov="" lus="" teb="" theem="" nrab="" (orr),="" qinlock="" kho="" pawg="" pab="" pawg="" tau="" nce="" piv="" nrog="" pawg="" placebo="" (orr:="" 9.="" 4%="" vs="" 0%,="" p="0.050" 4="">

Hais txog kev nyab xeeb, qhov tshwm sim tsis zoo tshaj plaws (GG gt; { 20%) yog cov plaub hau poob, qaug zog, xeev siab, mob plab, cem quav, myalgia, raws plab, tsis nco qab, palmoplantar erythrocyte paresthesia syndrome (PPES), thiab ntuav Cov. Ntawm cov neeg mob tau txais Qinlock, kev phiv tshuaj uas ua rau muaj kev tshem tawm mus tas li ntawm 8% ntawm cov neeg mob, kev cuam tshuam ntawm koob tshuaj vim kev phiv tshuaj tau tshwm sim hauv 24% ntawm cov neeg mob, thiab txo qhov koob tshuaj vim kev phiv tshuaj tshwm sim hauv { {3}}%. Qin Locke kho cov neeg mob.