Qinlock, Thawj Qhov Thib Plaub ntawm Cov Tshuaj Yeeb Tshuaj, Tshaj Tawm Tshiab Lub Sijhawm Zaum III, Thiab Tom Qab Ding Tshuaj Tau Qhia Tawm Rau Hauv Suav Teb!

Zai Lab tus khub Deciphera Pharmaceuticals nyuam qhuav tshaj tawm txoj kev kho plaub ntawm cov tshuaj tiv thaiv qog mob qin Qinlock (ripretinib) tshiab nyob rau hauv kev kho mob plab hnyuv ntu ntawm European Society of Oncology (ESMO) Ntiaj teb Gastrointestinal Cancer Conference (GIST) 2020 lub rooj sib tham tshiab cov ntaub ntawv los ntawm theem tseem ceeb III INVICTUS kev kawm (NCT03353753) ntawm GIST. Cov ntaub ntawv tshiab no yog los ntawm kev tshawb nrhiav qhov tseeb txog kev muaj mob uas tsis muaj sia nyob (PFS) thiab tag nrho cov neeg muaj sia nyob (OS) ntawm cov neeg mob uas hloov los ntawm cov placebo mus rau Qinlock tom qab tus kab mob nce zuj zus, qhia tias: Tom qab cov neeg mob hloov ntawm placebo mus rau Qinlock, lawv tau txais qhov tseem ceeb. cov kev pab kho mob.

Qinlock yog qhov ntau-spectrum KIT thiab PDGFRF kinase inhibitor. Thaum Lub Rau Hli 2019, Zaiding Pharmaceutical tau kos npe pom zoo nrog Deciphera kom tau txais daim ntawv tso cai tshwj xeeb rau Qinlock' s txoj kev loj hlob thiab nce qib hauv Greater Tuam Tshoj (Mainland Tuam Tshoj, Hong Kong, Macau thiab Taiwan).

INVICTUS yog ib qho kev xaiv (2: 1), ob chav dig muag, qhov chaw kawm tshuaj uas tau tshawb pom tias muaj 129 tus 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 qhov ua tau zoo thiab kev nyab xeeb ntawm Qinlock txheeb ze rau cov tshuaj placebo.

Cov ntaub ntawv luam tawm yav dhau los pom tau hais tias txoj kev tshawb no mus txog qhov tseem ceeb: qhov piv rau cov placebo, qhov kev vam meej-tsis muaj sia nyob ntawm Qinlock pawg kho mob tau ntev ntev (qhov nruab nrab PFS: 6.3 lub hlis vs 1.0 lub hlis), thiab kev pheej hmoo ntawm tus kab mob loj zuj zus lossis tuag yog qhov tseem ceeb txo los ntawm 85% (HR=0.15, p< 0.0001).="" raws="" li="" rau="" theem="" nrab="" kawg="" taw="" tes="" tag="" nrho="" cov="" kev="" ua="" neej="" nyob="" (os),="" qinlock="" kho="" pawg="" pab="" pawg="" tau="" ntev="" dua="" cov="" pab="" pawg="" placebo="" (qhov="" nruab="" nrab="" os:="" 15.1="" lub="" hlis="" vs="" 6.6="" lub="" hlis),="" thiab="" kev="" pheej="" hmoo="" ntawm="" kev="" tuag="" tau="" txo="" los="" ntawm="" 64%="" (hr="0.36," nominal.="" p="0.0004);" 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="" pab="" pawg="" kho="" mob="" tau="" nce="" siab="" piv="" nrog="" pawg="" placebo="" (orr:="" 9.4%="" vs="" 0%,="" p="">

Cov ntsiab lus tshawb nrhiav tau tshiab tshaj tawm ntawm lub rooj sib tham ESMO tau qhia tias cov neeg mob uas hloov los ntawm cov placebo kom qhib daim ntawv lo Qinlock kho mob muaj qhov nruab nrab PFS ntawm 4.6 lub hlis thiab nruab nrab OS ntawm 11.6 lub hlis. Cov ntaub ntawv no txuas ntxiv txhawb Qinlock' s lub peev xwm los muab cov txiaj ntsig kev kho mob zoo rau cov neeg mob uas muaj GIST siab. Rau cov neeg mob GIST uas yav tas los tau txais 3 txoj kev kho mob, Qinlock sawv cev tus qauv tshiab rau kev saib xyuas.

Cov tshuaj ua lag luam nquag ntawm Qinlock yog ripretinib, uas yog KIT / PDGFRin kinase hloov inhibitor, siv los kho KIT / PDGFRα-siv lub plab zom mov stromal hlav (GIST), mastocytosis mob (SM), thiab lwm yam mob qog nqaij hlav. 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 nrab KIT kev hloov pauv nyob hauv exons 9, 11, 13, 14, 17, 18 koom nrog hauv txoj hnyuv qog nqaij hlav thiab thawj KIT exosome 17 pom hauv SM Son D816V kev sib hloov. Ripretinib tseem inhibits thawj PDGFR ations hloov pauv hauv exons 12, 14, thiab 18, suav nrog lub plab hnyuv qog hlav uas cuam tshuam nrog kev hloov pauv hauv exon 18 D842V.

Thaum lub Tsib Hlis xyoo no, Qinlock tau txais US FDA pom zoo rau kev kho plaub-kab ntawm GIST siab heev. Qinlock yog qhov tsim nyog rau cov neeg mob neeg laus uas yav tas los kho 3 los yog ntau dua kinase inhibitors, suav nrog: imatinib (imatinib), sunitinib (sunitinib, regorafenib).

Nws yog tsim nyog teev tias Qinlock yog thawj cov tshuaj tshiab raug pom zoo rau kev kho plaub-kab ntawm GIST, khij qhov pib ua tau zoo. GIST yog cov qog uas pib tshwm sim hauv txoj hnyuv plab. Feem ntau ntawm cov neeg mob uas pib teb rau tsoos tyrosine kinase inhibitors yuav kawg ua rau qog vim tias kev hloov pauv theem ob. 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.

Thaum pom zoo Qinlock, Richard Pazdur, MD, Tus Thawj Coj ntawm FDA Center for Excellence in Onology thiab Coj Tus Thawj Coj ntawm Lub Chaw Haujlwm Oncology thiab Kab Mob ntawm FDA Center rau Kev Tshuaj Ntsuam Xyuas thiab Tshuaj, tau muab qhov ntsuas ntsuas siab:" hauv kev txhim kho GIST kev kho mob nyob rau hauv 20 xyoo dhau los, suav nrog plaub FDA-tau pom zoo rau kev kho mob - imatinib [2002], sunitinib [2006], regofenib [2013], avapritinib [avapritinib, 2020] - - Tab sis qee cov neeg mob tsis tau teb kev kho mob, thiab mob qog txuas ntxiv mus. Qinlock' s kev pom zoo rau kev ua lag luam muab cov kev xaiv kho mob tshiab rau cov neeg mob uas tau tso tawm FDA-tau pom zoo GIST kev kho tus qauv."