Merck tepotinib: lub ntiaj teb thawj zaug MET inhibitor, nws muaj qhov ua tau zoo hauv kev kho cov neeg mob nrog MET exon 14 dhia kev hloov pauv

Tsis ntev los no, qhov txiaj ntsig zoo ntawm ib qho tseem ceeb ntawm ib txhais tes Phase II VISION txoj kev tshawb nrhiav (NCT02864992) ntsuas tshuaj Merck KGaA' s lub hom phiaj tshuaj tua kab mob tshuaj tepotinib hauv kev kho mob tsis yog mob ntsws me me rau lub ntsws mob ntsws (NSCLC) tau luam tawm hauv New England Journal ntawm Tshuaj (NEJM). Tepotinib yog qhov xaiv tau MET inhibitor rau kev kho mob ntawm cov neeg mob nrog metastatic NSCLC nws cov qog muaj qhov hloov tau ua rau hla ntawm exon 14 ntawm MET gene (METex14).

Hais txog kev saib xyuas, tepotinib tau pom zoo hauv Nyij Pooj hauv lub Peb Hlis xyoo no thiab dhau los ua' s thawj qhov ncauj MET inhibitor. Nws cov lus qhia yog: kev kho mob ntawm qhov tsis tuaj yeem tiv thaiv, nce siab lossis rov qab los ntawm NSCLC cov neeg mob nrog hla kev hloov ntawm METex14. Tam sim no, tepotinib tab tom soj ntsuam qhov muaj feem thib xyuas los ntawm Asmeskas FDA thiab tau ua dhau los tau pom zoo Ua Yeeb Tshuaj Kho Kom Raug Mob (BTD).

Cov qauv hauv tshuaj lom neeg ntawm tepotinib (duab los ntawm: chemicalbook.com)

Hauv cov neeg mob NSCLC, splice qhov chaw hloov tshwm sim hauv kwv yees li 3-4%, ua rau muaj kev hloov pauv hauv exon 14 ntawm oncogenic tsav gene MET. Lub VISION txoj kev kawm tau soj ntsuam qhov ua tau zoo thiab kev nyab xeeb ntawm tepotinib hauv cov neeg mob no. Hauv txoj kev tshawb nrhiav, cov neeg mob uas muaj kev ua kom zoo lossis metastatic NSCLC uas tau lees paub tias tau hla kev hloov pauv hauv METex14 tau txais tepotinib monotherapy (500 mg ib hnub ib zaug). Qhov pib ntawm qhov xaus yog lub hom phiaj teb (ORR) rau cov neeg mob uas tau kuaj xyuas tus kheej thiab tau taug qab tsawg kawg 9 lub hlis. Tus nqi them rov qab tau txheeb xyuas raws li seb cov kua nqaij ua kua (LBx) los yog cov nqaij mos ua rau kuaj (TBx) kuaj pom METex14 hla kev hloov.

Txog Lub Ib Hlis 1, 2020, tag nrho ntawm 152 tus neeg mob tau txais kev kho mob tepotinib, thiab 99 tus neeg mob tau taug qab mus yam tsawg kawg 9 lub hlis. Hauv cov pawg muaj xyoob ntoo sib xyaw ua ke (LBx lossis TBx), ORR txiav txim los ntawm kev tshuaj xyuas kev ywj pheej yog 46% (95% CI: 36-57), thiab nruab nrab ntev teb (DOR) yog 11.1 lub hlis (95% CI: 7.2) -I). Ntawm 66 tus neeg mob hauv LBx biopsy pawg, ORR yog 48% (95% CI: 36-61), thiab hauv 60 tus neeg mob hauv pawg TBx biopsy, ORR yog 50% (95% CI: 37-63), thiab muaj 27 tus neeg mob Cov txiaj ntsig tau zoo tau los ntawm 2 txoj kev siv biopsy.

Cov kws tshawb nrhiav tshawb xyuas tau txheeb xyuas thiab txiav txim siab txog ORR kom muaj 56% (95% CI: 45-66), thiab tus nqi kho dua tshiab zoo ib yam tsis hais txog kev kho mob dhau los rau kev mob ntsws siab ntsws lossis mob ntsws cancer. Hauv qhov kev tshawb fawb no, cov kws tshawb nrhiav kev ntseeg tau ntseeg tias muaj tshwm sim ntawm qib 3 qhov xwm txheej tsis zoo uas cuam tshuam nrog kev kho tepotinib yog 28%, suav nrog peripheral edema (7%). Cov xwm txheej tsis zoo tshwm sim los ntawm kev txiav tawm tepotinib mus tas li hauv 11% ntawm cov neeg mob.

Hauv lub ntiaj teb, mob ntsws yog hom mob cancer feem ntau thiab ua rau mob cancer ploj tuag, nrog 2 lab kuaj mob thiab 1.7 lab tuag txhua xyoo. Cov kev hloov pauv ntawm MET cov paib ua kom pom tseeb (suav nrog kev hloov pauv ntawm MET exon 14 thiab MET amplification) tau pom nyob rau hauv ntau hom mob qog nqaij hlav, suav nrog NSCLC, uas cuam tshuam nrog qog cov kev coj tus cwj pwm thiab kev kuaj mob tsis zoo. Nws kwv yees hais tias kev hloov pauv ntawm MET kev taw qhia cov kev mob tshwm sim hauv 3-5% ntawm cov neeg mob NSCLC.

Tepotinib yog qhov ncauj MET kinase inhibitor pom hauv Merck. Nws tuaj yeem muaj zog thiab xaiv tau inhibit MET (noob) hloov pauv-suav nrog MET exon 14 dhia hloov, MET amplification lossis MET protein overexpression. Cov teeb liab oncogenic ntawm MET muaj qhov zoo los txhim kho qhov raug ntawm cov neeg mob qog hlav qog coj cov kev hloov tshwj xeeb MET. Ntxiv nrog rau NSCLC, Merck kuj tseem niaj hnub ntsuas tepotinib ua ke nrog kev kho tshiab rau lwm cov cim qhia qog.

Thaum lub Tsib Hlis Ntuj xyoo no, Novartis' MET inhibitor Tabrecta (capmatinib) tau txais kev pom zoo nrawm los ntawm Asmeskas FDA rau kev kho mob rau cov neeg mob NSCLC nrog METex14 dhia kev hloov pauv, suav nrog kev kho kab mob thawj zaug (naïve) cov neeg mob thiab yav tas los kho (kho mob) cov neeg mob, Tsis hais txog hom kev kho yav dhau los.

Nws tsim nyog teev tias Tabrecta yog thawj qhov kev kho mob tau pom zoo los ntawm Asmeskas FDA rau METex14 kev sib xyaw metastatic NSCLC. Hauv kev sim tshuaj kho mob, tag nrho cov lus teb (ORR) ntawm Tabrecta hauv kev kho mob-qhov tsis muaj zog thiab kho cov neeg mob METex14 kev sib hloov yog 68% thiab 41%, feem.

Hauv Suav teb, thaum kawg Lub Xya Hli xyoo no, Hutchison Tshuaj Cov Tshuaj MET inhibitor savolitinib tau suav nrog hauv kev tshuaj xyuas kev soj ntsuam ua ntej los ntawm National Food thiab Drug Administration. Cov tshuaj yog siv los kho cov neeg mob NSCLC nrog METex14 hla kev hloov pauv. Nov yog thawj daim ntawv thov tshuaj tshiab rau Volitinib thoob ntiaj teb thiab thawj cov ntawv thov tshuaj tshiab rau xaiv MET inhibitors hauv Suav teb.

Cov ntaub ntawv los ntawm Kev Tshawb Fawb Ntawm Theem II (NCT02897479) tshaj tawm ntawm ASCO Lub Rooj Sib Tham Txhua Xyoo hauv 2020 pom tias hauv cov neeg mob evaluable cov peev xwm ntawm volitinib nyob rau hauv kev kho METex14 hla kev hloov NSCLC, lub hom phiaj cov lus teb (ORR) yog 49.2%, thiab tus kab mob tswj tus nqi tswj (DCR)) Yog 93.4%, thiab lub sijhawm ntawm kev ncua (DOR) yog 9.6 hli.