Daim Qauv / CStone KIT Tus Neeg Txom Nyem Ayvakit (avapritinib): Tag Nrho Cov Kev Pov Tseg 75%!

CStone' s tus khub Blueprint Tshuaj yog lub tuam txhab ua lag luam tshuaj kho mob tsom rau kev kho cov mob kheesxaws, mob tsis tshua muaj thiab tshuaj tiv thaiv kab mob cancer. Tsis ntev los no, Blueprint Tshuaj tau tshaj tawm ntawm Asmeskas Lub Koom Haum rau Kev Tshawb Nrhiav Kab Mob Cancer (AACR) 2021 lub rooj sib tham txhua xyoo cov ntaub ntawv ntawm lub hom phiaj tshuaj tua kab mob Ayvakit (avapritinib) rau kev kho mob siab ntsig cov kab mob mastocytosis (SM) kev sau npe theem 2 PATHFINDER cov ntaub ntawv kuaj sim. Ayvakit yog cov muaj zog thiab xaiv cov tshuaj tiv thaiv ntawm D816V hloov pauv KIT (tus tsav tseem ceeb ntawm SM) thiab tam sim no tau tsim kho rau kev kho ntawm kev txawj ntse thiab tsis tau paub tshaj SM.

Hauv kev txiav txim siab ua ntej ntawm kev soj ntsuam PATHFINDER kev sim, raws li ntawm cov ntaub ntawv txiav-hnub ntawm Lub Rau Hli 23, 2020, 32 cov neeg mob uas tau txais thawj zaug ntawm 200 mg ib zaug ib hnub tuaj yeem raug tshuaj xyuas rau nws qhov ua tau zoo. Qhov kawg ntawm kev sau npe yog suav los ntawm tag nrho tus lej teb (ORR) thiab lub sijhawm teb (DOR) tshuaj xyuas los ntawm lub chaw. ORR txhais tau tias yog kev kho mob tag nrho, kho qee yam lossis kho kev kho mob ntawm kev ua tiav lossis ib feem ntawm kev rov qab los ntawm ntshav cov ntshav (CR / CRh). Txhua qhov kev qhia tawm hauv tsev kho mob tau lees paub. Ua ke nrog cov txiaj ntsig ntawm Kev Tsum Theem 1 EXPLORER sim, cov ntaub ntawv no tau txhawb nqa Blueprint' s txoj cai thov rau Ayvakit rau kev kho mob ntawm SM siab uas tau tshuaj xyuas nyob hauv Tebchaws Meskas thiab Europe.

Zuag qhia tag nrho, ntawm 32 tus neeg mob uas ua rau evaluable ua tau zoo, lub sij hawm taug qab nruab nrab yog 10.4 hlis, ORR yog 75% (95% CI: 57%, 89%), thiab 19% ntawm cov neeg mob ua tiav CR / CRh. Lub sij hawm nruab nrab ntawm kev kho mob mus rau kev kho tau yog 2 lub hlis, lub sij hawm nruab nrab ntawm kev kho mob kom ua tiav CRH yog 5.6 lub hlis, thiab cov tshuaj xyuas nruab nrab yog 10.4 lub hlis. Txhua yam kev ncua ntxiv. Cov ntaub ntawv no qhia tau tias txoj kev cawm siav tseem tob zuj zus rau lub sijhawm, ntawm tus nqi sib xws nrog EXPLORER mus sib hais.

Ib qho ntxiv, Ayvakit tau pom muaj zog thiab ua kom ntev li qhov tau txais txiaj ntsig kho nyob rau hauv ntau qhov ntsuas kev soj ntsuam kev ua haujlwm. Hauv cov ntaub ntawv qhia txog tus neeg mob tshiab (PRO) cov ntaub ntawv, raws li ntsuas los ntawm qib siab mastocytosis kev ntsuas tus yam ntxwv, tag nrho cov qhab nia ntawm cov neeg mob tom qab 40 lub lis piam ntawm kev kho mob Ayvakit tau zoo li qhov ntsuas qis (p< 0.001).="" raws="" li="" ntsuas="" los="" ntawm="" lub="" neej="" zoo="" ntawm="" cov="" lus="" nug="" ntawm="" european="" lub="" koom="" haum="" rau="" kev="" tshawb="" fawb="" thiab="" kev="" kho="" mob,="" tom="" qab="" ayvakit="" kev="" kho="" mob,="" qhov="" zoo="" ntawm="" lub="" neej="" qhia="" los="" ntawm="" cov="" neeg="" mob="" tau="" zoo="" dua.="" los="" ntawm="" ntau="" qhov="" kev="" ntsuas="" mast="" cell="" load="" ntsuas,="" ayvakit="" pom="" tau="" hais="" tias="" cov="" kab="" mob="" hlwb="" tryptase,="" hlwb="" pob="" txha="" mast="" hlwb,="" kit="" d816v="" allele="" load="" thiab="" spleen="" ntim="" tau="" txo="">

Ua raws li cov ntaub ntawv tau qhia tawm yav dhau los, 62 cov neeg mob koom nrog kev sim PATHFINDER zam tau Ayvakit zoo, thiab feem ntau cov kev tsis zoo (AE) tau qhia raws li qib 1 lossis 2. Cov xwm txheej tsis zoo tshaj plaws (≥15%) yog peripheral edema, periorbital edema, thrombocytopenia , ntshav tawm, neutropenia, raws plab, xeev siab, ntuav, thiab nkees. Peb tus neeg mob (5%) tau txiav tawm Ayvakit vim tias muaj feem cuam tshuam nrog kev kho mob, thiab feem ntau cov neeg mob (84%) tseem tau txais kev kho mob raws li cov ntaub ntawv txiav tawm hnub.

Daniel DeAngelo, MD, tus thawj coj ntawm Leukemia Department ntawm Dana-Farber Cancer Institute, tau hais tias:" Cov ntaub ntawv no txhim kho lub peev xwm ntawm Ayvakit los txhim kho cov qauv kev saib xyuas rau cov neeg mob uas muaj kab mob mastocytosis (SM), uas yog ib daim ntawv ntawm mast cell infiltration uas ua rau lub plab hnyuv siab raum. Tus kab mob muaj lub cim los ntawm kev puas tsuaj. Kuv tau txais kev txhawb siab los ntawm cov lus teb sai thiab kav ntev mus rau ntau lub ntsuas xws li mast cell load, cov neeg mob qhia tawm, thiab lub neej zoo. Tsis tas li ntawd, Ayvakit zoo pom zoo, tsuas yog 5% ntawm cov neeg mob tau txais kev kho mob-cuam tshuam txog kev txiav tawm ntawm cov tshuaj vim muaj cov xwm txheej tsis zoo. Vim tias Ayvakit tuaj yeem xaiv cov hom phiaj tseem ceeb ntawm tus kab mob, cov tshuaj muaj peev xwm hloov pauv cov kev kho mob rau cov neeg mob uas muaj SM."

Cov tshuaj nquag ua haujlwm ntawm Ayvakit yog avapritinib, uas tuaj yeem xaiv thiab muaj zog inhibit KIT thiab PDGFRA mutant kinases. Cov tshuaj yog ib hom kuv inhibitor tsim los tsom rau kev ua si lub zog kinase kev hloov pauv; tag nrho oncogenic kinases teeb liab los ntawm qhov kev hloov pauv no. Avapritinib tau pom tias muaj ntau yam kev cuam tshuam los tiv thaiv kev cuam tshuam rau GIST-cuam tshuam rau KIT thiab PDGFRA kev hloov pauv, suav nrog kev ua haujlwm muaj zog tiv thaiv kev hloov lub voj hloov uas cuam tshuam nrog kev tawm tsam kev pom zoo tam sim no.

Piv nrog kev pom zoo ntau cov kinase inhibitors, avapritinib yog qhov muaj kev xaiv ntau rau KIT thiab PDGFRA dua li lwm cov kinases. Ib qho ntxiv, avapritinib yog qhov tsim tshwj xeeb los xaiv khi thiab khi D816 hloov pauv KIT, uas yog ib tus neeg tsav tsheb muaj kabmob feem ntau kwv yees li 95% ntawm cov neeg mob uas muaj kab mob mastocytosis (SM). Kev tshawb nrhiav pom tau pom tias avapritinib tuaj yeem cuam tshuam KIT D816V nrog cov sub-nanomolar potency thiab muaj qhov tsawg ntawm kev ua haujlwm.

Hauv Tebchaws Meskas, European Union, thiab Tuam Tshoj, avapritinib tau pom zoo thaum Lub Ib Hlis 2020, Cuaj Hlis 2020, thiab Lub Plaub Hlis 2021 (Ayvakit, Ayvakyt) rau kev kho mob ntawm PDGFRA exon 18 hloov (suav nrog PDGFRA D842V kev hloov pauv) tsis tuaj yeem pom lossis cov neeg mob loj nrog metastatic lub plab zom mov qog nqaij hlav (GIST). Nws tsim nyog teev tias Ayvakit yog thawj qhov kev kho kom raug pom zoo rau GIST thiab thawj cov tshuaj nrog cov haujlwm siab tiv thaiv GIST nrog kev hloov pauv hauv exon 18 ntawm PDGFRA noob.

Tsis ntev dhau los, CStone Pharmaceuticals 'lwm qhov kev txiav txim siab rau kev siv tshuaj, Gavreto (pralsetinib), tau pom zoo los ntawm NMPA rau qib siab hauv cheeb tsam lossis metastatic uas tsis yog mob qog nqaij hlav hauv lub ntsws uas yav tas los tau txais platinum-muaj tshuaj kho mob rau kev hloov pauv hloov kho tshiab (RET) noob fusion-zoo cov kab mob ntsws uas tsis yog mob hlwb. (NSCLC) Kev kho mob ntawm cov neeg mob laus. Qhov no yog qhov pom zoo ntawm Tuam Tshoj' s thawj xaiv RET inhibitor thiab tseem yog thawj qhov kev lag luam pib ntawm CStone Pharmaceuticals.

Ob avapritinib thiab pralsetinib yog qhov hom phiaj tshuaj tsim los ntawm Blueprint Tshuaj. Qhov qub yog KIT / PDGFRA kinase inhibitor thiab tom kawg yog qhov muaj zog RET inhibitor. Nyob rau lub Rau Hli 2018, CStone Pharmaceuticals tau mus txog rau kev sib koom tes tshwj xeeb thiab kev pom zoo nrog Blueprint Medicines thiab tau txais kev txhim kho thiab kev ua lag luam txoj cai ntawm peb tus neeg sib tw xws li avapritinib thiab pralsetinib hauv Greater China (Mainland, Hong Kong, Macau, Taiwan).