Roche Rozlytrek tau txais kev pom zoo hauv EU: Kho NTRK fusion cov qog thiab ROS1-zoo mob ntsws!

Roche tsis ntev los no tshaj tawm tias Cov European Commission (EC) tau pom zoo cov tshuaj anticancer tshwj xeeb Rozlytrek (entrectinib) rau kev kho tus mob neurotrophic tyrosine receptor kinase (NTRK) gene fusion-positive solid hlav hlav hauv Pediatrics 12 xyoo thiab laus dua thiab cov neeg laus laus, tshwj xeeb: cov neeg mob uas muaj kab mob hauv zos, mob ntshav siab, lossis rov phais mob uas yuav ua rau muaj mob hnyav, thiab cov uas tsis tau txais NTRK inhibitors yav dhau los thiab tsis muaj cov kev kho mob txaus siab. Ntxiv rau, EC kuj pom zoo Rozlytrek rau kev kho mob ROS1-zoo, qib siab tsis-mob qog nqaij hlav hauv lub ntsws (NSCLC) cov neeg laus laus uas tsis tau dhau los ua ROS1 inhibitor. Hauv Tebchaws Meskas, Rozlytrek tau txais kev pom zoo rau ob qhov kev ntsuas saud thaum Lub Yim Hli 2019.

Rozlytrek yog Roche' s thawj lub qog-agnostic (tsis muaj feem cuam tshuam rau cov qog," cancer hom") kev kho mob. Nws tau qhia txog kev daws ncua ntev hauv ntau hom qog, nrog rau cov qog uas tau kis mus rau lub hlwb. Hauv Tebchaws Meskas thiab European Union, Rozlytrek tau txais txiaj ntsig yav dhau los Breakthrough Drug Designation (BTD) thiab Txoj Haujlwm Kev Tsim Tshuaj Tshuaj Ua Ntej (PRIME) rau kev kho mob NTRK fusion solid hlav. NTRK gene fusion tau pom nyob rau hauv cov lus qhia nyuaj los kho cov qog ua pob, nrog rau mob qog nqaij hlav, mob qog nqaij hlav cancer, mob qog ntshav qab zib, mob cancer mis, mob cancer thiab mob ntsws.

Rozlytrek' s kev pom zoo qhia tus nqi ntawm kev sib xyaw genomic tsom xam thiab cov tshuaj kho kom haum rau cov kev xaiv tus kheej rau kev kho mob rau cov neeg mob qog noj ntshav tsawg thiab nyuaj. Raws li kev kuaj genomic, Rozlytrek yuav muab kev kho zoo thib ib rau cov neeg mob NTRK lossis ROS1 noob fusion hauv ntau cov qog nqaij hlav, suav nrog cov neeg mob uas tau txhim kho lub hlwb metastases.

Nws tsim nyog teev tias Rozlytrek yog qhov thib peb tshuaj tua kab hauv tsev hauv nroog tau tso cai rau kev lag luam raws li cov biomarkers sib txawv ntawm ntau hom qog ntau dua li cov keeb keeb hlav. Ob qhov tshuaj ntxiv uas tau txais kev pom zoo" kev mob qog nqaij hlav tsis raug txwv" kev taw qhia yog: (1) Merck cov tshuaj tiv thaiv PD-1 Keytruda (Pembrolizumab), uas tau pom zoo rau xyoo 2017 rau kev kho mob ntawm microsatellites Stability (MSI-H) lossis mismatch kho cov qog (dMMR) cov qog, tau pom zoo thaum Lub Rau Hli 2020 los kho qhov siab cov qog hloov ua haujlwm (TMB-H) cov qog ua haujlwm; (2) Bayer' s lub hom phiaj tshuaj anticancer Vitrakvi (larotrectinib), Xyoo 2018, nws tau pom zoo kho NTRK noob fusion hlav.

Levi Garraway, MD, Tus Thawj Saib Xyuas Kev Kho Mob, Tus Thawj Coj ntawm Kev Tsim Kho Khoom Siv Hauv Ntiaj Teb, Roche tau hais tias:" Peb zoo siab tshaj tawm tias Rozlytrek tau pom zoo rau ob qhov ntsuas nyob rau hauv Tebchaws Europe, nqa txoj kev kho tshiab thiab zoo rau cov neeg mob NTRK thiab ROS1 noob fusion. Cov. Txoj kev, txawm hais tias lawv mob cancer tau kis mus rau lub hlwb. Qhov kev nce qib no sawv cev rau lwm txoj kev loj hlob hauv kev kho mob qog noj ntshav, uas tso cai rau peb kho qee cov gene tsav tsheb qog nqaij hlav tsis hais txog qhov chaw ntawm lub qog hauv lub cev. Roche tau cog lus rau kev txhawb nqa Tus Kheej li kev kho mob thiab hais txog cov kev xav tau kev kho mob tsis zoo ntawm cov neeg mob cancer uas tsis tshua muaj nyob thoob ntiaj teb."

Cov tshuaj kws tshaj tawm ntawm Rozlytrek yog entrectinib, uas yog tus xaiv tyrosine kinase inhibitor (TKI), tsom rau kev kho mob hauv zos lig lossis metastases nqa NTRK1 / 2/3 (encoding TRKA / TRKB / TRKC) lossis ROS1 gene fusion deev cov hlav. Entrectinib tuaj yeem hla cov ntshav-hlwb teeb meem, thaiv kev ua haujlwm kinase ntawm TRKA / B / C thiab ROS1 protein, thiab ua rau kev tuag ntawm cov qog ntshav nqa ROS1 lossis NTRK noob fusion. Entrectinib muaj cov teeb meem curative rau ob qho tib si thawj thiab metastatic tus kab mob CNS thiab tsis muaj kev phiv tawm ntawm lub hom phiaj. Tam sim no Roche tab tom tshawb xyuas qhov muaj peev xwm ntawm entrectinib los kho ntau yam mob ua cov qog, nrog rau NSCLC, mob qog nqaij hlav, mob sarcoma, mob qog nqaij hlav cancer, mob qog ntshav qab zib, mob plab hnyuv, thiab mob qog nqaij hlav tsis paub lub hauv paus (CUP).

Molecular qauv ntawm Rozlytrek nquag tshuaj tswj cov khoom siv tsis muaj tseeb (Duab cov duab: Wikipedia)

EU tau pom zoo Rozlytrek, raws li cov ntaub ntawv los ntawm ntau qhov kev tshawb fawb soj ntsuam, suav nrog cov piv txwv Ntu II kawm STARTRK-2, Ntu I kawm STARTRK-1, Ntu I kawm ALKA-372-001, thiab Theem I / II kev tshawb nrhiav hauv cov menyuam yaus STARTRK- NG. Cov kev tshawb fawb no qhia tau tias Rozlytrek muaj txiaj ntsig tiv thaiv ntau yam ntawm NTRK cov noob fusion-zoo cov qog ua haujlwm (suav nrog: sarcoma, mob qog nqaij hlav tsis muaj ntshav me, mob ua kua qaub-zoo li zais zis carcinoma (MASC), secretory thiab tsis-zais zis mob cancer mis, thyroid mob kheesxaws, mob hnyuv loj, mob hlav Endocrine hlav, mob qog nqaij hlav, hlav hlav cancer, kabmob kheesxaws endometrial, cholangiocarcinoma, mob plab hnyuv thiab neuroblastoma) thiab ROS1-zoo NSCLC muaj cov lus teb tau zoo. Cov kev tshuaj ntsuam tau zoo raws li nram no:

—— Kev Nyab Xeeb ntawm NTRK fusion-zoo cov qog: Rozlytrek' s zuag qhia tag nrho cov lus teb (ORR, 74 tus neeg mob) yog 63.5%, cov lus teb tau pom nyob hauv 13 ntau hom qog, thiab qhov nruab nrab ntawm cov lus teb (DoR) yog 12.9 Hlis (thaj: 9.3- tsis tau hu).

—— Kev Nyab Xeeb ntawm ROS1-zoo nce qib NSCLC: Rozlytrek' s tus lej teb tag nrho (ORR; 94 tus neeg mob, soj qab taug qab 12 lub hlis) yog 73.4%, thiab nruab nrab DoR yog 16.5 lub hlis (thaj tsam: 14.6 lub hlis-28.6 lub hlis). Ntawm 161 cov neeg mob taug qab mus txog rau 6 lub hlis, suav nrog 29% ntawm cov neeg mob lub hauv nruab nrog cev (CNS) metastases, ORR yog 67.1%.

—— Cov neeg mob nruab nrog cov hlab ntsha hauv nruab nrab (CNS) metastases ntawm lub hauv paus: Cov lus teb rau Rozlytrek kho tau pom, thiab kev kho mob ntawm ORR hauv NTRK thiab ROS1 cov neeg mob yog 62.5% thiab 79.2%, ua ntu zus.

——Txoj kev mob rau cov menyuam yaus: Rozlytrek txo cov qog hauv txhua tus menyuam yaus thiab cov hluas nrog NTRK noob fusion (n=5) (ORR=100%), thiab 2 ntawm lawv ua tiav kev zam tag nrho (CR=40%). Cov hom phiaj tau txais kev zam txim tau pom nyob hauv 2 cov neeg mob qog qib siab, thiab 1 rooj plaub muaj kev kho mob tag nrho.

Rozlytrek muaj kev tiv thaiv zoo, thiab cov kev mob tshwm sim tsis zoo xws li: qaug zog, cem quav, saj hloov (ua pa tsw phem), o (tsaus ntuj), kiv taub hau, raws plab, xeev siab, mob hlwb (hnov lub suab tsis zoo), ua tsis taus pa (ua pa) , lub cev hnyav tuaj, lub cev muaj zog ntau ntxiv, mob, qhov muag ntawm lub hlwb, ntuav, ntuav, kub cev.