Asmeskas FDA pom zoo Blueprint / Roche Gavreto los kho mob qog nqaij hlav cancer

Roche tsis ntev los no tshaj tawm tias Tsoom Fwv Meskas Khoom Noj thiab Tshuaj (FDA) tau pom zoo rau qhov tseeb oncology tshuaj-RET kinase inhibitor Gavreto (pralsetinib) rau kev kho mob rau menyuam yaus thiab cov neeg laus uas muaj mob qog nqaij hlav cancer hnub nyoog ≥12 xyoo. : (1) Cov neeg mob uas twb muaj lawm los yog mob RET-mutated medullary thyroid carcinoma (MTC) xav tau kev kho mob tsis raug; (2) Cov neeg mob uas muaj lub siab ntev lossis ua kom zoo ntawm RET-mutated medullary thyroid carcinoma (MTC) xav tau kev kho mob rau lub cev, radioiodine refractory (yog tias radioiodine tsim nyog), dhau los lossis metastatic RET fusion-zoo cov thyroid caj pas mob cancer. Cov kev ntsuas tau pom zoo tau txais nyob hauv FDA kev pom zoo sai cov txheej txheem raws li cov ntaub ntawv tau kawm los ntawm Ntu I / II ARROW kawm. Txuas ntxiv kev pom zoo rau cov ntsuas no yuav ua raws li cov ntawv pov thawj thiab cov lus piav qhia txog cov txiaj ntsig tau hauv cov kev sim ua pov thawj.

Gavreto yog qhov tawm ib zaug ib zaug RET qhov ncauj tsom kev kho uas tsim thiab tsim los ntawm Blueprint Cov Tshuaj los xaiv thiab xaiv qhov kev hloov RET ntau ntau (fusions thiab hloov pauv, suav nrog kev kwv yees kev hloov tshuaj-yeeb tshuaj) uas ua rau muaj ntau hom qog nqaij hlav. Lub Xya Hli xyoo no, Roche thiab Blueprint tau kos npe txog $ 1.7 txhiab daim ntawv tso cai thiab kev koom tes pom zoo, tau txais Gavreto' cov cai tshwj xeeb sab nraud Tebchaws Asmeskas (tsis suav Suav Tebchaws Suav) thiab kev sib koom ua lag luam nyob hauv Tebchaws Meskas cov khoom lag luam. Raws li daim ntawv cog lus yav dhau los uas tau kos npe nrog Blueprint, CStone Cov Lag Luam Muaj Ntawv Tso Cai ntawm Gavreto hauv Greater Suav Teb.

Thaum lub Cuaj Hlis xyoo no, Gavreto tau txais kev pom zoo nrawm los ntawm Asmeskas FDA rau kev kho mob rau cov neeg mob cov neeg laus uas muaj cov kabmob mob ntsws uas tsis yog mob hlwb (NSCLC) uas tau lees tias yog RET fusion-positive los ntawm FDA-pom zoo kuaj.

Li ntawm 10-20% ntawm cov neeg mob papillary cov qog nqaij hlav cancer (feem ntau cov thyroid mob cancer) nqa RET fusion-zoo cov qog, thiab li ntawm 90% ntawm cov neeg mob uas muaj MTC (ib yam tsis tshua muaj mob qog nqaij hlav cancer) nqa RET hloov. Kev kuaj pom ntawm cov neeg biomarkers rau RET fusion thiab hloov pauv tuaj yeem pab txiav txim siab seb cov neeg mob puas tsim nyog rau kev kho mob Gavreto.

Levi Garraway, MD, Roche Tus Thawj Saib Xyuas Kev Noj Qab Haus Huv thiab Tus Thawj Tuav Haujlwm ntawm Cov Khoom Siv Thoob Ntiaj Teb hais tias: "Peb zoo siab ua haujlwm nrog Blueprint kom coj txoj haujlwm tshiab tseem ceeb no rau cov neeg mob qog nqaij hlav cancer nrog rau qee yam kev hloov RET. Tam sim no Gavreto tau pom zoo rau kev siv Ntau hom qog nqaij hlav hloov los ntawm RET qhia txog peb txoj kev mob siab rau kev kho mob tus kheej thiab kho txhua tus neeg muaj mob qog nqaij hlav."

Qhov kev pom zoo no yog ua raws li cov txiaj ntsig ntawm Kev Tshawb Fooj 1 / II ARROW. Cov ntaub ntawv qhia tau hais tias tsis hais tus neeg mob tau raug kho yav tas los, thiab tsis hais tus xeeb ceem ntawm RET kev hloov pauv, kev kho Gavreto qhia tau hais tias lub sijhawm ua haujlwm hauv chaw khomob ntev. Cov txiaj ntsig tshwj xeeb muaj xws li hauv qab no: (1) Ntawm 55 tus neeg mob nrog RET hloov pauv metastatic MTC uas yav tas los tau txais cabozantinib thiab / lossis vandetanib, tag nrho cov lus teb tau txais (ORR) ntawm Gavreto kho yog 60% (95% CI: 46%, 73 %)), qhov nruab nrab nruab nrab ntawm kev teb (DoR) tseem tsis tau txog (95% CI: 15.1 hlis, NE). (2) Ntawm 29 tus neeg mob nrog RET-mutated advanced MTC uas yav dhau los tsis tau txais cabozantinib thiab / lossis vandetanib thiab raug txheeb xyuas tias tsis tsim nyog rau kev saib xyuas tus qauv, ORR yog 66% (95% CI: 46%, 82%). (3) Ntawm 9 tus neeg mob RET fusion-zoo metastatic thyroid cancer, ORR yog 89% (95% CI: 52%, 100%), thiab nruab nrab DoR tsis ncav cuag (95% CI: NE, NE). Hauv qhov kev tshawb fawb no, qhov tshwm sim tsis zoo tshaj plaws (≥25%) hauv cov neeg mob uas cov qog hloov pauv los ntawm RET yog cem quav, nce ntshav siab (tawg), nkees, mob musculoskeletal, thiab mob plab zawv.

Cov qauv tsim ntawm pralsetinib (duab los ntawm: aobious.com)

RET-qhib lub fusions thiab hloov pauv yog qhov tseem ceeb tsav tsheb rau ntau hom mob cancer, suav nrog NSCLC thiab MTC. RET fusion koom nrog li 1-2% ntawm NSCLC cov neeg mob thiab li 10-20% ntawm cov neeg mob papillary thyroid carcinoma (PTC), thaum RET cuam tshuam cuam tshuam txog li 90% ntawm cov neeg mob MTC siab. Tsis tas li ntawd, kev hloov pauv tsawg tsawg RET kuj tseem tau pom hauv kev mob qog nqaij hlav cancer, mob cancer mis, mob qog nqaij hlav thiab lwm yam mob qog nqaij hlav, thiab RET fusion kuj tau pom nyob rau hauv cov neeg mob uas siv tshuaj, EGFR-mutated NSCLC.

pralsetinib tau tsim los ntawm pab neeg tshawb fawb ntawm Blueprint Tshuaj raws li nws lub tsev qiv ntawv khoom ntiag tug. Hauv cov kev tshawb fawb preclinical, pralsetinib yeej ib txwm qhia sub-nanomolar titers tiv thaiv cov feem ntau RET noob fusions, ua kom muaj kev cuam tshuam kev hloov thiab kev hloov pauv. Ntxiv rau, qhov xaiv ntau ntawm pralsetinib rau RET ua tau zoo dua piv nrog kev pom zoo multi-kinase inhibitors. Ntawm lawv, cov kev ua haujlwm ntawm pralsetinib yog ntau dua 90 lub sij hawm siab dua li ntawm VEGFR2. Los ntawm inhibiting cov kev hloov pauv thawj thiab theem nrab, pralsetinib cia siab tias yuav kov yeej thiab tiv thaiv qhov tshwm sim ntawm kev tshawb nrhiav tshuaj. Cov txheej txheem kev kho mob no cia siab kom ua tiav kev kho mob ntev ntev hauv cov neeg mob uas muaj RET sib txawv, thiab muaj kev nyab xeeb zoo.

Nws tsim nyog teev tias Eli Lilly Retevmo (selpercatinib) yog thawj zaug pom zoo RET inhibitor. Cov tshuaj tau tsim los ntawm Loxo Oncology, lub tuam txhab oncology nyob hauv Eli Lilly thiab tau pom zoo los ntawm Asmeskas FDA hauv lub Tsib Hlis xyoo no. Nws yog siv los kho cov neeg mob nrog peb hom qog nrog kev hloov caj ces (hloov pauv los yog fusions) hauv RET gene: tsis mob qog nqaij hlav hauv hlwb tsawg (NSCLC), Medullary thyroid carcinoma (MTC), lwm yam mob qog nqaij hlav cancer.

Hais txog kev noj tshuaj, Retevmo noj ntawm qhov ncauj ob zaug ib hnub, nrog lossis tsis noj mov. Retevmo yog thawj cov tshuaj kho tau pom zoo tshwj xeeb rau cov neeg mob cancer nqa RET caj hloov. Cov tshuaj yog qhov tsim nyog rau kev kho mob ntawm: (1) Cov neeg laus cov neeg mob siab heev lossis metastatic NSCLC; (2) Cov neeg mob uas muaj MTC tshaj los yog metastatic uas muaj hnub nyoog ≥12 xyoos thiab xav tau kev kho mob tas li; (3) Muaj hnub nyoog ≥12 xyoos thiab xav tau kev kho mob zoo thiab muaj cov neeg mob hluav taws xob nrog cov mob RET fusion-zoo cov qog nqaij hlav cancer uas tau tso tseg tsis kho cov tshuaj iodine lossis tsis tsim nyog rau kev kho hluav taws xob rau iodine. Nws yog qhov tshwj xeeb tshaj tawm tias txog li 50% ntawm RET fusion-positive NSCLC cov neeg mob yuav muaj cov kab mob qog hlwb metastases. Ntawm cov neeg mob uas muaj lub hauv paus ntawm lub hlwb metastases, Retevmo tau qhia tias muaj zog, nrog kev kho mob sab nrauv (CNS-ORR) kom txog 91% (n=10/11).