Cov European Union pom zoo Qinlock (ripretinib): thawj plaub kab GIST tshuaj tau tsim tawm hauv Suav teb!

Zai Lab tus khub Deciphera Pharmaceuticals tsis ntev los no tshaj tawm tias European Commission (EC) tau pom zoo rau cov tshuaj tiv thaiv kab mob Qinlock (ripretinib) rau plaub-kab kho mob plab hnyuv stromal hlav (GIST). Cov tshuaj tshwj xeeb yog tsim rau: yav tas los tau txais 3 Cov neeg laus uas muaj GIST siab heev tau kho nrog ib lossis ntau dua kinase inhibitors (xws li imatinib).

Thaum lub Cuaj Hlis 2021, raws li ESMO-EURACAN-GENTURIS cov txheej txheem kev kho mob, Qinlock tau ntxiv los ua pawg thib plaub ntawm cov neeg mob GIST uas tau txais.imatinib, sunitinib, thiabregorafenibtab sis muaj kab mob kis los yog intolerant rau cov tshuaj no. Kab kev npaj kho mob. Hauv Phase 3 INVICTUS txoj kev tshawb fawb, Qinlock kev kho mob txo qis kev pheej hmoo ntawm kev kis kab mob lossis tuag los ntawm 85%, thiab pom cov txiaj ntsig tseem ceeb ntawm kev noj qab haus huv tag nrho.

Ripretinib yog KIT / PDGFRα kinase hloov regulator inhibitor rau kev kho mob ntawm KIT / PDGFRα-driven gastrointestinal stromal qog (GIST), systemic mastocytosis (SM) thiab lwm yam qog noj ntshav. Thaum Lub Rau Hli 2019, Zai Lab tau txais daim ntawv tso cai tshwj xeeb los ntawm Deciphera rau kev txhim kho thiab kev txhawb nqa ntawm Repetinib hauv Greater Tuam Tshoj (Mainland Tuam Tshoj, Hong Kong, Macau thiab Taiwan). Thaum Lub Peb Hlis 2021, Qinlock tau pom zoo los ntawm National Medical Products Administration (NMPA) rau kev kho mob ntawm cov neeg laus cov neeg mob nrog GIST siab heev uas tau kho nrog 3 lossis ntau dua kinase inhibitors suav nrog imatinib. Thaum Lub Peb Hlis 2021, Qinlock kuj tau pom zoo los ntawm Hong Kong Lub Tsev Haujlwm Saib Xyuas Kev Noj Qab Haus Huv.

Steve Hoerter, Thawj Tswj Hwm thiab CEO ntawm Deciphera, tau hais tias:" Qhov kev pom zoo EU ntawm Qinlock yog qhov kev pom zoo thib yim thoob ntiaj teb. Cov tshuaj hloov pauv no yog qhov tseem ceeb rau cov neeg mob uas muaj GIST siab heev hauv EU uas xav tau kev kho mob tshiab. Peb tos ntsoov yuav ua haujlwm nrog cov thawj coj tswj hwm kom ntseeg tau tias txhua tus neeg mob tsim nyog uas tuaj yeem tau txais txiaj ntsig los ntawm Qinlock kho tau txais kev kho mob sai li sai tau."

Qhov kev pom zoo no yog ua raws li cov txiaj ntsig tau zoo ntawm qhov kev tshuaj ntsuam tseem ceeb ntawm theem 3 INVICTUS txoj kev tshawb fawb, nrog rau cov txiaj ntsig kev nyab xeeb los ntawm INVICTUS txoj kev tshawb fawb thiab kev kawm theem 1. INVICTUS yog ib qho randomized (2: 1), ob-dig muag, placebo-tswj theem 3 txoj kev tshawb fawb, tso npe rau tag nrho 129 tus neeg mob uas yav tas los tau txais ntau yam kev kho mob (xws li tsawg kawgimatinib, sunitinib, regorafenib) ) Hauv cov neeg mob uas muaj GIST siab heev, qhov ua tau zoo thiab kev nyab xeeb ntawm Qinlock txheeb ze rau cov placebo tau soj ntsuam.

Cov txiaj ntsig kev tshawb fawb tseem ceeb tshaj tawm thaum Lub Yim Hli 2019 tau pom tias txoj kev tshawb fawb tau mus txog qhov kawg ntawm qhov kawg: Piv nrog rau cov placebo pab pawg, pab pawg kho mob Qinlock tau muaj sia nyob ntev dua (piv txwv li PFS: 6.3 hli vs 1.0 lub hlis), kab mob kev loj hlob lossis kev tuag. kev pheej hmoo raug txo qis los ntawm 85% (HR=0.15, p< 0.0001).="" nyob="" rau="" hauv="" cov="" nqe="" lus="" ntawm="" theem="" nrab="" kawg="" kev="" ciaj="" sia="" taus="" (os),="" pawg="" qinlock="" kho="" mob="" tau="" ntev="" dua="" li="" cov="" placebo="" pab="" pawg="" (nruab="" nrab="" os:="" 15.1="" lub="" hlis="" vs="" 6.6="" lub="" hlis),="" thiab="" kev="" pheej="" hmoo="" ntawm="" kev="" tuag="" raug="" txo="" los="" ntawm="" 64%="" (hr="0.36," nominal="" p.="0.0004);" nws="" yog="" ib="" qho="" tsim="" nyog="" sau="" cia="" tias="" os="" cov="" ntaub="" ntawv="" hauv="" pab="" pawg="" placebo="" suav="" nrog="" cov="" ntaub="" ntawv="" ntawm="" cov="" neeg="" mob="" uas="" hloov="" mus="" rau="" qinlock="" kev="" kho="" mob="" tom="" qab="" tau="" txais="" cov="" placebo.="" tag="" nrho="" cov="" lus="" teb="" tus="" nqi="" (orr)="" ntawm="" lwm="" qhov="" kawg="" theem="" kawg="" tau="" txhim="" kho="" zoo="" hauv="" qinlock="" pab="" pawg="" kho="" mob="" piv="" nrog="" cov="" placebo="" pawg="" (orr:="" 9.4%="" vs="" 0%,="" p="">

Cov txiaj ntsig kev soj ntsuam zaum kawg tshaj tawm ntawm ESMO lub rooj sib tham hauv 2020 tau qhia tias cov neeg mob uas hloov los ntawm cov placebo mus rau qhib-label Qinlock kev kho mob muaj qhov nruab nrab PFS ntawm 4.6 lub hlis thiab qhov nruab nrab OS ntawm 11.6 lub hlis. Cov ntaub ntawv no ntxiv dag zog rau Qinlock' lub peev xwm los muab cov txiaj ntsig zoo rau kev kho mob rau cov neeg mob uas muaj GIST siab heev. Rau cov neeg mob GIST uas yav dhau los tau txais peb txoj kev kho mob, Qinlock sawv cev rau tus qauv tshiab ntawm kev saib xyuas.

INVICTUS cov kev tshawb fawb

Qinlock' cov khoom siv tshuaj nquag yogripretinib, uas yog KIT / PDGFRα kinase hloov regulator inhibitor, siv los kho KIT / PDGFRα-driven gastrointestinal stromal qog (GIST), systemic mastocytosis (SM) thiab lwm yam mob qog noj ntshav. ripretinib tshwj xeeb yog tsim los txhim kho kev kho mob ntawm cov neeg mob plab hnyuv stromal hlav los ntawm inhibiting qhov dav-spectrum mutations ntawm KIT thiab PDGFRα. Ripretinib tuaj yeem thaiv qhov pib thiab theem nrab KIT kev hloov pauv hauv exons 9, 11, 13, 14, 17, thiab 18 koom nrog hauv plab hnyuv stromal qog thiab thawj KIT exon No. 17 pom hauv SM Sub D816V kev hloov pauv.ripretinibtseem inhibits thawj PDGFRα kev hloov pauv hauv exons 12, 14, thiab 18, suav nrog cov qog nqaij hlav hauv plab uas cuam tshuam nrog D842V kev hloov pauv hauv exon 18.

Thaum lub Tsib Hlis 2020, Qinlock tau pom zoo los ntawm US FDA rau plaub kab kev kho mob ntawm GIST siab heev. Qinlock yog qhov tsim nyog rau cov neeg mob laus uas yav dhau los tau kho nrog 3 lossis ntau dua kinase inhibitors, suav nrog: imatinib,sunitinib, thiabregorafenib.

Nws yog ib qho tsim nyog hais tias Qinlock yog thawj cov tshuaj tshiab tau pom zoo rau kev kho mob thib plaub ntawm GIST, uas yog qhov tseem ceeb tshaj plaws. GIST yog ib qho qog uas tshwm sim hauv plab hnyuv. Feem ntau cov neeg mob uas pib teb rau cov tshuaj tyrosine kinase inhibitors thaum kawg yuav tsim cov qog nqaij hlav vim kev hloov pauv theem nrab. Hauv Phase III INVICTUS txoj kev tshawb fawb, Qinlock tau qhia kev ntseeg tau cov txiaj ntsig kev kho mob raws li kev muaj sia nyob tsis muaj sia nyob (PFS) thiab tag nrho cov ciaj sia taus (OS), thiab muaj kev nyab xeeb zoo thiab kev zam. Cov tshuaj yuav yog plaub kab GIST muab kev kho tshiab tseem ceeb.

Hauv kev pom zoo Qinlock, Richard Pazdur, MD, Tus Thawj Coj ntawm FDA Oncology Center of Excellence thiab Tus Thawj Coj Tus Thawj Coj ntawm Lub Chaw Haujlwm Saib Xyuas Kev Noj Qab Haus Huv thiab Kab Mob ntawm FDA's Center for Drug Evaluation and Research, tau hais ntau txog: “Txawm hais tias muaj kev vam meej hauv kev txhim kho. ntawm GIST kev kho mob dhau 20 xyoo dhau los, suav nrog Plaub FDA-pom zoo cov kev kho mob-imatinib [2002], sunitinib [2006], regorafenib[2013], avapritinib [avapritinib, 2020]—Tab sis qee tus neeg mob tsis teb rau kev kho mob thiab qog nqaij hlav txuas ntxiv mus. Qinlock' qhov kev pom zoo rau kev lag luam muab kev kho mob tshiab rau cov neeg mob uas tau tso tseg FDA-pom zoo GIST txoj kev kho mob."