Retevmo Yog Qhov Siv Tau Kho Tau Ntau Yam RET Fusion Mob Cancer!

Eli Lilly tsis ntev los no tshaj tawm cov ntaub ntawv rau qhov tseeb oncology tshuaj Retevmo (selpercatinib) Ntu 1/2 kev tshawb fawb soj ntsuam LIBRETTO-001 thawj zaug ntawm Lub Koom Haum Asmeskas Kev Tshawb Nrhiav Cancer (AACR) 2021 lub rooj sib tham txhua xyoo, qhia pom tias Retevmo ntxiv rau kev mob ntsws thiab cov qog mob qog Ua kom yoog tiv thaiv qog thiab ua kom muaj kev nyab xeeb nyob rau hauv ntau ntawm RET fusion-positive advanced siab hlav (suav nrog cov tshuaj ntau ntxiv rau lub plab zom mov [GI] malignancies): kev kho mob kho tau pom nyob rau hauv 9 yam mob qog nqaij hlav cancer (ORR) yog 47%; cov tshuaj nruab nrab rov qab yog 13 lub hlis, thiab lub sijhawm nruab nrab ntawm kev teb (DOR) tseem tsis tau mus txog. Ntawm 15 tus neeg mob hauv qhov kev zam txim, 11 txuas ntxiv ua kom muaj kev zam txim. Hauv cov kev tshawb fawb no, kev nyab xeeb ntawm Retevmo tau nyob nrog txoj kev paub kev nyab xeeb ntawm cov tshuaj.

Kev tshawb fawb LIBRETTO-001 yog qhov kev tshawb fawb loj tshaj plaws uas tshuaj xyuas RET inhibitor kev kho mob rau cov neeg mob qog nqaij hlav uas hloov RET. Cov neeg mob sau npe suav nrog cov neeg mob uas muaj ntau yam mob qog uas tsis tau txais kev kho mob (kev kho mob thaum xub thawj) thiab tau txais kev kho mob ntau yam. Xws li RET fusion-positive tsis muaj cov kabmob ntsws mob ntsws me tshaj plaws (NSCLC), RET-mutated medullary thyroid carcinoma (MTC), RET fusion-zoo cov qog nqaij hlav cancer, thiab lwm yam kev mob qog nrog RET hloov.

Raws li cov ntaub ntawv los ntawm pawg mob ntsws ntsws thiab cov mob qog nqaij hlav cancer hauv kev tshawb nrhiav, Retevmo tau txais kev pom zoo los ntawm Asmeskas FDA rau lub Tsib Hlis 2020 rau kev kho cov qog uas muaj kev hloov caj ces (hloov mus los yog fusions) hauv kev tshwj xeeb (hloov kho cov noob thaum hloov ntshav) , RET genes) Muaj 3 hom kev mob qog ua haujlwm: cov qog nqaij hlav cancer tsis yog mob ntsws me me (NSCLC), medullary thyroid carcinoma (MTC), thiab lwm yam mob qog ua cancer. Hauv European Union, selpercatinib tau pom zoo thaum Lub Ob Hlis 2021 thiab muag raws li cov npe lag luam Retsevmo.

Retevmo / Retsevmo yog thawj cov tshuaj kho tau pom zoo tshwj xeeb rau cov neeg mob qog nqaij hlav nrog RET hloov kev hloov kho. Cov tshuaj yog xaiv RET kinase inhibitor uas tuaj yeem tiv thaiv RET kinase thiab tiv thaiv kev loj hlob ntawm cov qog nqaij hlav cancer.

David Hyman, Tus Thawj Saib Xyuas Kev Noj Qab Haus Huv ntawm Eli Lilly Oncology, tau hais tias:" Peb txaus siab nthuav Retevmo' s cov pov thawj hauv RET fusion-zoo mob qog nqaij hlav dua li mob ntsws thiab cov qog hlav. Cov ntsiab lus txhawb nqa no, suav nrog nyuaj-rau-kho tus mob plab hnyuv, ua kev txhawb nqa Muaj ntau qhov pov thawj ntxiv tias RET fusion yog qhov muaj peev xwm kho tau nyob rau hauv ntau hom qog ntshav. Cov kev tshawb pom ntxiv no qhia qhov tseem ceeb ntawm ntau ntawm cov qog cov yam ntxwv hauv kev mob qog ntshav siab. Peb cia siab tias yuav tham txog cov haujlwm tshiab no nrog cov cai tswj hwm xyoo no cov ntaub ntawv."

Hauv Kev Tsum Theem 1/2 LIBRETTO-001 kev sim, raws li kev ua tiav ntawm lub sijhawm thaum lub Cuaj Hlis 19, 2020, tag nrho ntawm 32 tus neeg mob cov neeg mob uas muaj 12 qhov tshwj xeeb RET fusion-positive advanced cancer hom tau muaj nyob hauv txoj kev tshawb fawb thiab yuav tau taug qab kom txog rau lub Peb Hlis 2021 19th. Kab mob kheesxaws kho muaj xws li mob qog nqaij hlav cancer, mob cancer nyuv, mob cancer mis, mob cancer ntawm lub mis, sarcoma, carcinoid, mob nqaij hlav cancer neuroendocrine, mob plab hnyuv loj, xanthogranuloma, mob cancer ntawm zes qe menyuam, mob ntsws mob ntsws sarcoma, Ntawm 32 tus neeg mob, 62.5% muaj mob qog nqaij hlav hauv plab (txhais tau tias yog leeg ntshav [n=9], mob hnyuv [n=9], txoj hnyuv me [n=1], lub qhov quav neuroendocrine [n=1]). Hauv tag nrho 32 tus neeg mob, cov lus teb pom zoo (ORR) yog 47% (95% CI: 26-65%). Kev lees txais qhov tseeb tau pom nyob hauv 9 qhov tshwj xeeb RET fusion-positive advanced cancer hom. Cov nruab nrab rov qab yog 13 lub hlis. Nruab nrab kom ntev teb (DoR) tsis tau txog. Ntawm cov neeg mob hauv kev zam txim, 73% (11/15) tswj kev so kom txaus.

Kev nyab xeeb ntawm cov neeg mob hauv pawg neeg sib koom ua ke no yog ua tau zoo nrog kev paub txog kev nyab xeeb ntawm Retevmo. Hauv cov pawg no, muaj qhov tshwm sim tsis zoo tshaj plaws (TEAEs) ntawm txhua qib (≥20%) thaum kho mob suav nrog aspartate aminotransferase (AST) / alanine aminotransferase (ALT), qhov ncauj qhuav, thiab kub siab, raws plab, qaug zog, xeev siab thiab mob plab Cov. Tsis muaj ib tug neeg mob hauv pab pawg no muab kho ntxiv vim tias muaj kev kho mob tshwm sim tsis zoo.

Vivek Subbiah, MD, Tsev Kawm Qib Siab Texas MD Anderson Cancer Center, tau hais tias:" Txawm hais tias nws tsis nquag, RET fusion tshwm sim hauv ntau hom qog nqaij hlav uas tsis yog mob ntsws thiab mob qog nqaij hlav cancer. Cov neeg mob no tsis muaj kev pom zoo kho hom phiaj. Txog ntawm tus neeg tsav tsheb sib deev ntawm nws kev mob qog noj ntshav. Cov txiaj ntsig no tau qhia qhov muaj peev xwm ntawm selpercatinib rau cov neeg mob ntawm cov neeg mob no thiab rov hais dua qhov tseem ceeb ntawm kev soj ntsuam dav dav kom paub qhov tseeb ntawm cov tsav tsheb oncogenic (suav nrog RET fusion)."

Nws kwv yees tias RET fusion tshwm sim nyob rau thaj tsam li 2% ntawm cov tsis mob qog nqaij hlav cancer hauv lub cev me me (NSCLC), 10-20% ntawm papillary thyroid cancer (PTC) thiab lwm yam mob qog, thiab lwm yam mob qog nqaij hlav (xws li mob qog nqaij hlav hauv plab. ) pawg neeg tsawg; RET cov ntsiab lus hloov tau tshwm sim nyob hauv kwv yees li 60% ntawm medullary thyroid carcinoma (MTC). RET fusion thiab RET taw tes hloov qog nqaij hlav tsuas yog cia siab rau kev ua kom RET kinase los tswj lawv txoj kev loj hlob thiab kev ciaj sia. Qhov kev tso siab no feem ntau hu ua" oncogene quav", ua rau cov qog no tiv taus cov tshuaj loj molecule inhibitors uas lub hom phiaj RET. rhiab.

Retevmo / Retsevmo yog qhov muaj zog, qhov ncauj, xaiv tau zoo heev, rov qab kho thaum hloov kho (RET) kinase inhibitor rau kev kho mob ntawm cov neeg mob qog nqaij hlav nrog mob RET txawv txav. Lub RET gene yog ib qho proto-oncogene uas thim rov qab thaum lub sijhawm hloov ntshav, yog li nws lub npe. Cov keeb no nthuav tawm lub cell membrane receptor tyrosine kinase uas nws qhov txawv txav yog ib qho kev tsav tsis tshua muaj ntawm ntau hom qog. Retevmo / Retsevmo yog tsim los rau inhibit ntuj RET teeb liab kis thiab cov kev cia siab xav tau tshuaj tiv thaiv kev tiv thaiv, thiab yog tsim rau kev kho mob rau cov neeg mob uas tsis meej RET kinase hauv cov hlav.

Hauv Tebchaws Meskas, FDA tau tso cai yav dhau los selpercatinib kev tsim nyog tshuaj (BTD) rau kev kho mob ntawm peb hom neeg mob, tshwj xeeb: (1) Tus kab mob loj zuj zus thiab xav tau tom qab tau txais platinum-muaj tshuaj kho thiab PD-1 lossis PD -L1 qog tshuaj tiv thaiv kab mob Kev kho mob Lub cev Kev tiv thaiv kab mob (kev kho mob nrog lub cev) cov neeg mob nrog metastatic RET fusion-positive NSCLC; (2) RET mutant MTC cov neeg mob uas tau hloov zuj zus tom qab kev kho yav dhau los thiab tsis muaj kev xaiv kev kho mob tau yooj yim thiab xav tau kev kho mob tsis raug; (3) yav dhau los tau txais lwm txoj kev xaiv Cov neeg mob uas muaj mob RET fusion-zoo ua cov thyroid mob qog uas muaj tus kab mob siab dua thiab tsis muaj kev xaiv lwm txoj kev kho tau xav tau kev kho mob raws kab ke.

Selpercatinib yog yeeb tshuaj ntawm Loxo Oncology. Eli Lilly tau txais Loxo Oncology rau US $ 8 txhiab nyob rau lub Ib Hlis 2019. Lub Kaum Ob Hlis 2019, Eli Lilly tau pib ua tiav ob theem kev kuaj mob ntawm selpercatinib: LIBRETTO-431 kev sim rau kev kho mob RET fusion-positive NSCLC cov neeg mob, thiab LIBRETTO-531 rau kev kho mob tshiab nyuam qhuav RET-mutant MTC cov neeg mob. Txhua qhov kev sim yuav tau 400 tus neeg mob.