Cov txiaj ntsig ntawm Phase II Kev Tshawb Fawb ntawm FGFR Inhibitors hauv Kev Kho Mob ntawm Tuam Tshoj Biliary Tract Cancer Cov Neeg Mob

Tsis ntev los no, Innovent tshaj tawm cov txiaj ntsig ntawm Phase II kawm ntawmPemigatinibHauv Suav cov pej xeem uas muaj tus mob cholangiocarcinoma siab heev hauv daim ntawv tshaj tawm hauv 2021 ESMO. Yav dhau los, cov tshuaj' daim ntawv thov kev lag luam rau kev kho mob cholangiocarcinoma siab heev tau txais los ntawm NMPA thaum Lub Xya Hli 9 thiab tau suav nrog hauv kev tshuaj xyuas tseem ceeb rau Lub Xya Hli 12.

Txoj kev tshawb no yog ib qho qhib, ib sab caj npab, ntau qhov chaw kho mob theem II, uas yog lub hom phiaj los ntsuas qhov ua tsis tiav.Pemigatinibyav dhau los tsawg kawg yog ib qho kev kho mob, fibroblast kev loj hlob zoo tshaj plaws receptor 2 (FGFR2) noob fusion lossis rov kho dua Kev ua tau zoo thiab kev nyab xeeb hauv Suav cov neeg mob zoo nrog cov kab mob cholangiocarcinoma siab heev. Nws yog ib qho kev xeem sib txuas hauv tsev ntawm FIGHT-202 txoj kev kawm (INCB 54828-202, NCT02924376).

Raws li lub Ib Hlis 29, 2021, thawj feem yog PK txoj kev tshawb fawb hauv cov pej xeem Suav, uas suav nrog tag nrho 3 cov ntsiab lus ntawm cholangiocarcinoma, thiab qhov thib ob suav nrog tag nrho 31 tus neeg mob cholangiocarcinoma uas tau zoo rau FGFR2 noob fusion lossis rov kho dua. Raws li kev kho mob txhua 3 lub lis piam (ob lub lis piam ntawm cov tshuaj, ib lub lim tiam ntawm kev tshem tawm cov tshuaj) ntawm qhov ncauj 9 mg (ib ntu 1) lossis 13.5 mg (ib ntu 2) ntawmPemigatinibkom txog rau thaum muaj kab mob loj zuj zus tuaj, kev tsis haum tshuaj lom lossis tshem tawm ntawm kev pom zoo, thiab lwm yam. Lub ntsiab lus tseem ceeb ntawm kev sim tshuaj ntsuam xyuas yog lub hom phiaj teb tus nqi (ORR) ntsuas los ntawm IRRC nyob rau hauv qhov thib ob.

Hauv qhov thib ob ntawm 30 tus neeg mob uas muaj txiaj ntsig zoo (1 qhov kev kawm tau raug cais tawm ntawm cov pej xeem uas ntsuas tau vim tias lub hauv paus chaw kuaj pom tias FGFR noob hloov pauv ntau tsis tau raws li cov txheej txheem xaiv), 15 tus neeg mob tau ua tiav kev tshem tawm kab mob, thawj qhov kawg ORR mus txog. 50% (95% CI: 31.3%, 68.7%). Ntawm qhov kev soj ntsuam nruab nrab ntawm 5.13 lub hlis, 12 tus neeg mob tseem nyob hauv kev zam txim, thiab lub sijhawm nruab nrab ntawm kev zam txim (DOR) tseem tsis tau txog (95% CI: 3.4, NR). Raws li lub sijhawm kawg ntawm cov ntaub ntawv, qhov nruab nrab ntawm kev muaj sia nyob tsis pub muaj sia nyob (PFS) ) Cov ntaub ntawv tseem tsis tau paub tab, tsuas yog 6 qhov xwm txheej ntawm PFS tshwm sim, thiab tus kab mob tswj hwm tus nqi (DCR) yog 100% (95% CI: 88.4%, 100%).

Kev soj ntsuam kev nyab xeeb suav nrog tag nrho 34 tus neeg mob. Raws li hnub txiav tawm cov ntaub ntawv, txhua qhov kev kawm tau tshaj tawm tsawg kawg yog ib qho kev kho mob ntsig txog qhov tsis zoo (TRAE). Feem ntau TRAE yog hyperphosphatemia (73.5%) thiab xerostomia. (55.9%) thiab alopecia (50.0%), qhov tshwm sim ntawm TRAE ≥ qib 3 yog 14.7%. Peb qhov kev kawm tau tshaj tawm cov xwm txheej tsis zoo (SAE), uas yog lub qhov quav polyps, lub siab ua haujlwm tsis zoo, thiab cholangitis. Tsis muaj cov xwm txheej phem ua rau tuag thiab kev kho mob thaum lub sijhawm sim.

FIGHT-202 txoj kev tshawb fawb tau tso npe rau 108 tus neeg mob nrog cholangiocarcinoma nrog FGFR2 fusion lossis rov kho dua. Cov kawm tau txaisPemigatinib13.5 mg kev kho qhov ncauj, ORR yog 37% (95% CI: 27.94%, 46.86%), suav nrog 4 kis ntawm kev tshem tawm tag nrho (3.7%) thiab 36 qhov kev tshem tawm ib nrab (33.3%), qhov nruab nrab Lub sij hawm ntawm kev zam txim (DOR) yog 8.08 lub hlis (95% CI: 5.65, 13.14), qhov nruab nrab ntawm kev ua kom tsis muaj sia nyob (PFS) yog 7.03 lub hlis (95% CI: 6.08, 10.48), pemigatinib tuaj yeem ua rau mob qog noj ntshav ntev ntev, nrog rau ib qho nruab nrab Lub zuag qhia tag nrho cov ciaj sia taus (OS) yog 17.48 lub hlis (95% CI: 14.42, 22.93).

Hais txog kev nyab xeeb, cov txiaj ntsig tau qhia tiaspemigatinibzoo zam txim. Ntawm lawv, hyperphosphatemia yog qhov tshwm sim tsis zoo tshaj plaws, nrog qhov tshwm sim ntawm 58.5%. 68.7% ntawm cov neeg kawm tau ntsib qib 3 lossis siab dua qhov kev tsis zoo. Raws li lub sij hawm nyiam, hypophosphatemia (14.3%) yog qhov feem ntau tshaj tawm. Lwm tus suav nrog arthralgia thiab qhov ncauj mucositis (6.1% txhua), mob plab, qaug zog, thiab hyponatremia (tag nrho 5.4%), lwm cov xibtes thiab plantar o syndrome thiab hypotension, tshwm sim hauv 4.8% thiab 4.1%, feem.

Pemigatinibyog ib qho muaj zog thiab xaiv qhov ncauj inhibitor ntawm FGFR subtype 1/2/3 tsim los ntawm Incyte. Thaum Lub Kaum Ob Hlis 2018, Innovent thiab Incyte tau mus txog kev koom tes hauv kev sib koom tes ntawm peb tus neeg sib tw tshuaj tau tshawb pom thiab tsim los ntawm Incyte, suav nrog pemigatinib, uas yog nyob rau hauv kev sim tshuaj. Raws li cov lus pom zoo, Cinda Bio muaj cai tsim thiab ua lag luam pemigatinib hauv Mainland Tuam Tshoj, Hong Kong, Macau thiab Taiwan.

Nyob rau lub Plaub Hlis 2020, FDA tau nrawm qhov kev pom zoo ntawm Incyte' s Pemazyre rau kev kho mob ntawm cov neeg laus uas tau kho yav dhau los / metastatic lossis tsis tuaj yeem kho FGFR2 noob fusion / rov kho cholangiocarcinoma. Hauv Nyij Pooj, Pemazyre tau txais kev pom zoo los kho cov neeg mob uas tsis tuaj yeem kho mob qog noj ntshav (BTC) nrog FGFR2 fusion gene thiab tau mob zuj zus tom qab siv tshuaj khomob. Hauv Tebchaws Europe, Pemazyre tau txais kev pom zoo rau kev kho mob ntawm FGFR2 fusion lossis rov kho dua hauv zos lossis metastatic cholangiocarcinoma thiab cov neeg laus uas muaj tus kabmob kis tau tom qab tsawg kawg ib qho kev kho mob yav dhau los."