Zai Lab ripretinib tau suav nrog hauv kev tshuaj xyuas kev soj ntsuam tseem ceeb los ntawm Lub Xeev Tsoom Fwv Saib Xyuas Kev Tshuaj!

Zai Lab tau tshaj tawm tsis ntev los no tias Lub Chaw Saib Xyuas Tshuaj (CDE) ntawm National Medical Products Administration (NMPA) tau tso cai KIT / PDGFR α kinase inhibitor ripretinib txoj kev saib xyuas kev muaj feem rau kev tsim cov tshuaj tshiab tshiab. Cov tshuaj no yog siv los kho cov neeg laus cov neeg laus uas muaj pob txha caj qaum (GIST) uas tau kho nrog 3 lossis ntau dua kinase inhibitors suav nrog imatinib.

Nws yog tsim nyog sau cia tias thaum kawg Lub Xya hli ntuj xyoo no, CStone' s KIT / PDGFRα kinase inhibitor avapritinib (avapritinib) ob daim ntawv teev npe tshuaj tshiab rau kev kho mob GIST tau suav nrog kev tshuaj xyuas kev muaj feem thib los ntawm CDE.

Raws li nqe lus GG; Kev ntsuas rau Kev Ua Haujlwm ntawm Kev Sau Npe Tshuaj" (Daim Ntawv Sau Tseg No. 27 ntawm Lub Xeev Tsoom Fwv Tswj Xyuas Kev Ua Lag Luam) tau siv los ntawm Lub Xeev Tsoom Fwv Saib Xyuas Tshuaj (Drug Drug Administration) rau Lub Xya Hli 1 thiab" tau pib siv thaum Lub Xya Hli 7 (No. 82 ntawm 2020), Tuam Tshoj tau tsim qauv kev tshuaj xyuas thiab pom zoo tso cai los txhawm rau txhim kho thiab nkag mus rau kev lag luam ntawm cov tshuaj tshiab nrog tus nqi tseem ceeb thiab cov mob xav tau sai sai. Raws li cov lus qhia ntawm cov ntawv tswjfwm no, lub chaw tso cai pom zoo yuav saib xyuas thiab tshuaj xyuas cov tshuaj uas tau txais kev tshuaj xyuas uas tau txais ua ntej los txiav txim luv thiab sijhawm pom zoo.

Ripretinib yog tyrosine kinase hloov tswj cov tshuaj tiv thaiv uas siv qhov tshwj xeeb dual lub tswv yim ntawm kev nqis tes ua los tswj lub kinase hloov thiab qhib cov voj, yog li cuam tshuam loj heev rau KIT thiab PDGFRα mutant kinases. Ripretinib inhibits qhov hloov pauv thawj thiab theem nrab ntawm KIT exons 9, 11, 13, 14, 17 thiab 18 hauv GIST, thiab kev hloov pauv ntawm exon 17 D816V nyob rau hauv micocytosis mauj (SM). Ripretinib tseem inhibits kev hloov pauv thawj hauv exons 12, 14 thiab 18 ntawm PDGFR some nyob rau qee cov neeg ntawm GIST, suav nrog D842V hloov pauv hauv exon 18. Cov tshuaj tau tsim los kho cov qog nqaij hlav los ntawm KIT thiab / lossis PDGFRα, suav nrog GIST, SM thiab lwm yam mob qog noj ntshav.

Reptinib (kev ua lag luam npe Qinlock) tau pom zoo rau kev lag luam hauv Tebchaws Meskas, Canada, thiab Australia txog kev kho plaub ntawm cov neeg mob cov neeg laus uas muaj GIST siab heev, tshwj xeeb: cov neeg mob laus uas tau txais yav dhau los 3 lossis ntau dua kinase inhibitors, suav nrog: Iraq Martinib [imatinib], sunitinib [sunitinib], regorafenib [regorafenib]. Nws tsim nyog teev tias Qinlock yog thawj cov tshuaj tshiab raug pom zoo rau kev kho plaub ntawm GIST.

Thaum Lub Rau Hli 2019, Zai Lab tau kos npe rau daim ntawv tso cai pom zoo nrog Deciphera kom tau txais txoj cai los tsim thiab ua lag luam ripretinib hauv Greater China (Suav Teb Main, Tuam Tshoj, Hong Kong, Macau thiab Taiwan). Hauv Suav teb, muaj ntau dua 30,000 tus neeg mob GIST tshiab txhua xyoo. GIST cov neeg mob, tshwj xeeb tshaj yog cov uas tau txhim kho tsis kam rau cov kev kho mob yav dhau los, tseem muaj cov kev xav tau tsis tseem ceeb. Raws li kev pom zoo ntawm Asmeskas FDA tam sim no thiab cov ntaub ntawv zoo tshaj plaws ntawm kev tshawb fawb INVICTUS (NCT03353753), reputinib cia siab tias yuav hloov pauv tam sim no ntawm kev kho mob ntawm cov neeg mob GIST hauv Suav.

INVICTUS yog ib qho kev xaiv (2: 1), ob chav dig muag, tshuaj placebo, tswj hwm thoob ntiaj teb ntau lub chaw theem III, kawm tag nrho ntawm 129 tus neeg mob uas yav tas los tau txais ntau yam kev kho mob (suav nrog tsawg imatinib, sunitinib, Regorafenib) hauv cov neeg mob nrog GIST siab heev, tau txheeb xyuas cov kev ua tau zoo thiab kev nyab xeeb ntawm Qinlock tus txheeb ze rau cov placebo.

Cov txiaj ntsig tau pom tias qhov kev tshawb fawb tau mus txog qhov kawg: piv nrog pab pawg placebo, Qinlock pawg kho mob tau muaj kev muaj sia nyob ntev dua tsis muaj kev ciaj sia (cov tshuaj nruab nrab PFS: 6.3 lub hlis vs 1.0 lub hlis), thiab txo qhov tseem ceeb ntawm kev pheej hmoo ntawm tus mob lossis kev tuag los ntawm 85% (HR=0.15, p< 0.0001).="" hais="" txog="" kev="" ua="" tiav="" theem="" ob="" kawg="" tag="" nrho="" kev="" ua="" neej="" nyob="" (os),="" qinlock="" pab="" pawg="" kho="" mob="" 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="" cov="" ntaub="" ntawv="" os="" hauv="" cov="" pawg="" placebo="" suav="" nrog="" cov="" ntaub="" ntawv="" ntawm="" cov="" neeg="" mob="" uas="" hloov="" mus="" rau="" qinlock="" kev="" kho="" mob="" tom="" qab="" tau="" txais="" cov="" tshuaj="" placebo.="" tus="" lej="" teb="" tag="" nrho="" (orr)="" ntawm="" lwm="" qhov="" xaus="" kev="" ua="" tiav="" tau="" zoo="" dua="" hauv="" qinlock="" pab="" pawg="" kho="" mob="" piv="" nrog="" pawg="" placebo="" (orr:="" 9.4%="" vs="" 0%,="" p="">

Hais txog kev nyab xeeb, qhov tshwm sim tsis zoo tshaj plaws (GG gt; 20%) yog plaub hau poob, nkees, xeev siab, mob plab, cem quav, myalgia, raws plab, tsis qab los noj mov, palmoplantar liab ntshav cell paresthesia syndrome (PPES), thiab ntuav Cov. Hauv cov neeg mob uas tau txais Qinlock kho, cov kev tsis zoo uas ua rau muaj kev cuam tshuam tas mus li hauv 8% ntawm cov neeg mob, kev cuam tshuam kev txhaj tshuaj vim qhov tshwm sim tsis zoo tshwm sim hauv 24% ntawm cov neeg mob, thiab txo qhov koob tshuaj vim tias qhov tshwm sim tsis zoo tshwm sim hauv 7% ntawm cov neeg mob. Ntawm cov neeg mob kho los ntawm Qinlock.

CStone' s KIT / PDGFRα kinase inhibitor avapritinib muaj ntawv tso cai los ntawm Blueprint Tshuaj. Nyob rau lub Rau Hli 2018, lub tuam txhab tau mus txog tshwj xeeb kev koom tes thiab kev tso cai pom zoo nrog Blueprint Medicines, thiab tau txais kev txhim kho thiab ua lag luam txoj cai ntawm peb tus neeg sib tw ua yeeb tshuaj suav nrog avapritinib hauv Greater China (Mainland, Hong Kong, Macau, Taiwan).

Lub Ib Hlis xyoo no, avapritinib (lub npe lag luam Ayvakit) tau pom zoo los ntawm Asmeskas FDA rau kev kho mob tsis muaj kev tiv thaiv lossis metastatic GIST cov neeg laus cov neeg mob uas muaj kev hloov pauv hauv exon 18 ntawm PDGFRA noob (suav nrog PDGFRA D842V hloov). Nws yog tsim nyog sau cia tias thaum Lub Tsib Hlis xyoo no, FDA tau xa tsab ntawv teb tiav (CRL) rau lwm daim ntawv thov tshuaj tshiab rau avapritinib, tsis kam lees pom txoj kev kho plaub rau GIST cov cim.

Nws tsim nyog teev tias Ayvakit yog thawj qhov kev npliag rau txoj kev pom zoo rau kev kho mob ntawm cov neeg mob GIST, thiab thawj cov tshuaj zoo heev rau PDGFRA exon 18 mutant GIST.

Tsuas yog peb lub hlis tom qab avapritinib tau pom zoo los ntawm Asmeskas FDA rau kev lag luam, CStone Pharmaceuticals tau xa cov ntawv thov tshuaj tshiab rau avapritinib hauv Taiwan thiab Suav. Lub Plaub Hlis xyoo no, NMPA tau lees txais yuav ib daim ntawv thov tshuaj tshiab rau avapritinib, npog 2 qhov taw qhia, uas yog: (1) Rau kev kho mob ntawm cov neeg mob nqa platelet-derived loj hlob receptor alpha (PDGFRA) exon 18 hloov pauv (suav nrog PDGFRA D842V kev hloov pauv) cov neeg laus nrog phais rov ua dua lossis metastatic GIST; (2) Cov neeg laus nrog cov plaub-kab tsis tuaj yeem pom lossis metastatic GIST.

Muaj kwv yees li 1-1.5 / 100,000 (14,000-21,000) tus neeg Gist mob tshiab hauv Suav teb txhua xyoo, thiab kwv yees li 90% ntawm cov kab mob pathogenic ntawm cov neeg mob GIST muaj feem cuam tshuam nrog KIT lossis PDGFRA noob hloov pauv. Kev tshawb nrhiav NAVIGATOR tshaj tawm pom tias avapritinib muaj qhov kev sib tham tag nrho (ORR) ntawm 86% hauv cov neeg mob uas muaj GIST siab nrog PDGFRA exon 18 hloov (suav nrog D842V hloov), thiab hauv plaub-kab GIST cov neeg mob, ORR tau mus txog 22%.