Roche Rozlytrek tabtom yuav raug pom zoo los ntawm European Union los kho ntau hom NTRK fusion cov qog thiab ROS1-zoo ntsws mob qog!

Roche tau tshaj tawm tsis ntev los no hais tias Lub Chaw Haujlwm Saib Xyuas Kev Noj Tshuaj hauv Tebchaws Europe (EMA) rau Cov Khoom Siv Kho Mob rau tib neeg siv (CHMP) tau tshaj tawm cov lus pom zoo, hais tias muaj kev pom zoo rau lub hom phiaj tiv thaiv mob qog noj ntshav Rozlytrek (entrectinib) siv cov tshuaj neurotrophic tyrosine saum toj no. kinase (NTRK) gene fusion positive solid tumor tumor pediatric thiab neeg laus cov neeg mob, tshwj xeeb: kev mob hauv zos, mob metastasis lossis phais mob phais yuav ua rau muaj mob hnyav, thiab tsis tau txais NTRK inhibitors, tsis txaus siab Kev xaiv kho rau cov neeg mob. Ntxiv rau, CHMP pom zoo rau kev pom zoo ntawm Rozlytrek rau kev kho mob ROS1-zoo, qib siab tsis-mob qog nqaij hlav hauv hlwb tsawg (NSCLC) cov neeg laus laus uas tsis tau txais yav dhau los ROS 1 inhibitors.

Tam sim no, CHMP' s cov lus yuav raug xa mus rau European Commission (EC) rau kev tshuaj xyuas, uas xav tias yuav txiav txim siab zaum kawg kev txiav txim siab tsis pub dhau 2 lub hlis tom ntej. Yav dhau los, EMA tau tso cai Rozlytrek' s Qhov Muaj Peev Xwm Siv Tshuaj (PRIME) rau NTRK fusion cov qog. NTRK gene fusion tau pom muaj nyob hauv ntau hom qog uas nyuaj los kho, nrog rau mob qog nqaij hlav cancer, mob qog nqaij hlav cancer, mob salivary adenocarcinoma, mob cancer mis, mob qog nqaij hlav cancer, thiab mob ntsws.

Hauv Tebchaws Meskas, Rozlytrek tau dhau los tau tso cai rau kev quav tshuaj yeeb tshuaj (BTD) rau kev kho NTRK fusion solid hlav. Cov tshuaj tau txais kev pom zoo nrawm los ntawm FDA hauv lub Yim Hli 2019: (1) rau kev kho mob ntawm 1 2 - cov laus uas tsis muaj tam sim no muaj txoj kev kho zoo. saum toj no neurotrophic tyrosine receptor kinase (NTRK) gene fusion positive pediatric thiab cov neeg laus cov neeg mob uas muaj cov qog cov pob txha dhau los. (2) Rau kev kho mob ntawm cov neeg mob laus ROS 1 - zoo metastatic tsis mob me me ntawm cov ntsws mob ntsws (NSCLC).

Roche Tus Thawj Saib Xyuas Kev Kho Mob, Lub Taub Hau ntawm Kev Tsim Khoom Siv Ntiaj Teb, Levi Garraway, MD, tau hais tias:" Thaum pom zoo, Rozlytrek yuav dhau los ua Roche thawj cov qog-agnostic hauv Tebchaws Europe, uas tsis cuam tshuam nrog hom qog nqaij hlav."" kev kho. Yog li, qhov keeb kwm no qhia txog txoj kev txhim kho tshiab hauv kev siv tshuaj rau tus kheej. Raws li kev kuaj genomic, Rozlytrek yuav muab kev kho zoo thib ib rau cov neeg mob NTRK lossis ROS 1 noob fusion hauv ntau cov qog nqaij hlav, suav nrog metastases uas twb tshwm sim ntawm cov neeg mob."

Rozlytrek yog qhov tshuaj tua kabmob thib peb ntawm cov khw muag khoom los ntawm cov tshuaj biomarker ntawm ntau hom qog tsis dua li cov nqaij ntawm cov qog ntawm cov qog keeb kwm, cim cov qauv tshiab ntawm" qog-agnostic" kev txhim kho tshuaj mob qog noj ntshav. Ob qhov tshuaj ntxiv tau pom zoo" qog agnosticism" qhov taw qhia yog: ({{2}}) Hauv 2 0 {{2}} 7, Merck' s Keytruda (Corrida, Pabrizumab) tau pom zoo rau kev kho mob ntawm microsatellite siab tsis khov (MSI-H) Los yog mismatch kho kev puas tsuaj (dMMR) qog; (2) Hauv 2 0 {{2}} 8, Bayer tsom cov tshuaj tua kabmob kheesxaws Vitrakvi (larotrectinib) tau pom zoo kho NTRK noob fusion hlav.

Cov tshuaj ua ntu zus ntawm Rozlytrek yog entrectinib, uas yog xaiv tyrosine kinase inhibitor (TKI), kev kho hom phiaj rau lub zos theem lig lossis metastasis nqa NTRK 1 / 2 / 3 (encoding TRKA / TRKB / TRKC) lossis ROS 1 gene fusion Cov nqaij hlav tawv. entrectinib tuaj yeem hla cov ntshav-hlwb teeb meem, thaiv kev ua haujlwm kinase ntawm TRKA / B / C thiab ROS 1 protein, ua rau kev tuag ntawm cov kabmob hlwb nqa ROS 1 lossis NTRK noob fusion. entrectinib muaj txiaj ntsig rau ob qho tib si thawj thiab cov kabmob ua rau muaj tus kabmob CNS thiab tsis muaj kev xav ua haujlwm tawm ntawm lub hom phiaj. Tam sim no, Roche tabtom 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 tsis paub mob cancer thawj (CUP).

CHMP cov lus pom zoo, raws li cov ntaub ntawv los ntawm ntau qhov kev tshawb fawb soj ntsuam, suav nrog kev kawm tseem ceeb nyob rau qib II STARTRK-2, theem Kuv kawm STARTRK-1, theem Kuv kawm ALKA-372-001, thiab I / II hauv cov neeg mob menyuam yaus pib pib STARTRK- NG. Hauv kev soj ntsuam ntxaws ntxig, kev ua tau zoo ntawm Rozlytrek hauv kev kho ntau yam mob qog noj tau raug ntsuas. Cov txiaj ntsig tau qhia tias:

—— Kev cuam tshuam ntawm NTRK fusion-positive cov qog nqaij hlav (n=74): Rozlytrek' s zuag qhia tag nrho cov lus teb (ORR) yog 63. 5%. Lub hom phiaj teb rau Rozlytrek kho tau pom nyob rau hauv 14 cov khoom sib txawv ntawm cov qog, thiab cov sij hawm nruab nrab ntawm cov lus teb (DoR) yog 12. 9 lub hlis (thaj tsam: 9 .3 -tsis tsis tau txog). Ntawm 31 tus neeg mob uas tau txais kev zam txim, 61% tau lub sijhawm ncua ntawm ≥ 9 hlis. Qhov tseem ceeb tshaj plaws, kev kho mob kev kho mob ntawm Rozlytrek kuj tau pom nyob hauv cov neeg mob nrog cov hlab ntsha hauv nruab nrog cev (CNS) metastases ntawm lub hauv paus, nrog kev kho mob siab ntawm 5 0%.

—— Kev Nyab Xeeb ntawm ROS 1 - zoo NSCLC: Qib Siab NSCLC: Rozlytrek&# {{1}}; tus lej teb tag nrho (kev soj qab nruab nrab ntawm 94 cov neeg mob rau {{{{{6 }}}} lub hlis, ORR) yog 73. 4%, thiab nruab nrab lub sijhawm teb (DoR) yog 16. 5 lub hlis (thaj tsam: {{17 .} {{{6).} {{{{17)} 0}} hlis -28. {{1 0}} Lub Hlis). Ntawm cov 16 1 cov neeg mob uas tau taug qab rau {{1 0}} lub hlis, suav nrog {{1 5}}% ntawm cov neeg mob uas muaj lub paj hlwb (CNS) ) metastasis, ORR yog {{1 6}}. 1%.

-Rozlytrek kev kho kev kho tau pom nyob rau hauv ob qho tib si NTRK thiab ROS 1 cov neeg mob nrog CNS metastasis ntawm lub hauv paus.

——Cov neeg mob, Rozlytrek txo cov qog (ORR=100%) hauv txhua qhov NTRK noob fusion (n=5) menyuam yaus thiab tub ntxhais hluas, thiab 2 ntawm lawv ua tiav kev zam tag (CR=40%). Lub homphiaj zam txim tau pom nyob hauv 2 cov neeg mob uas muaj lub siab loj, ntawm cov 1 rooj plaub tau kho tag nrho.

Hauv cov kev tshawb fawb no, Rozlytrek tau raug soj ntsuam los kho ntau hom mob qog, suav nrog: mob sarcoma, mob qog nqaij hlav tsis muaj ntshav me me, mob qog nqaij hlav siab lub qe menyuam lub cev nqaij daim tawv nqaij (MASC), zais ntshav thiab tsis-secretory mis mob cancer, mob qog nqaij hlav cancer, mob qog nqaij hlav cancer, neuroendocrine Tumor , mob kheesxaws pancreatic, mob kheesxaws ntawm zes qe menyuam, mob cancer endometrial, cholangiocarcinoma, mob plab hnyuv thiab neuroblastoma.

Rozlytrek muaj lub siab thev taus zoo. Feem ntau cov kev mob tshwm sim ntawm cov tshuaj muaj xws li: qaug zog, quav tawv, hloov kev saj (halitosis), o (edema), kiv taub hau, raws plab, xeev siab, mob lub cev tsis txaus siab (hnov lub suab tsis zoo), ua tsis taus pa (mob ua pa), ntshav tsis txaus, hnyav nce, nce ntxiv ntshav creatinine, mob, pom kev tsis nco qab, ntuav, hnoos, ua npaws.