Novartis Capmatinib pom zoo los kho NSCLC domestic Hengrui thiab lwm lub tuam txhab tshuaj kom xa cov tshuaj MET tsom tshuaj.

Novartis tshaj tawm tias Capmatinib (lub npe lag luam Tabrecta) tau pom zoo los ntawm Asmeskas Chaw Tswj Xyuas Khoom Noj thiab Tshuaj (FDA) thaum Lub Tsib Hlis 6, 2020 rau kev kho mob metastatic tsis mob me me ntawm tes ntsws mob ntsws (NSCLC) ntawm MET exon 14 dhia hloov kev laus Tus neeg mob siab. Nyob rau tib lub sijhawm, FDA tau pom zoo ib yam khoom uas tshawb pom hom hloov caj dab hauv qab kev lag luam npe hu ua FoundationOne CDx. Capmatinib tau muab tsub rau lub npe ntawm kev so kho los ntawm FDA. Lub Ob Hlis 11, 2020, Novartis tshaj tawm tias FDA tau lees txais Capmatinib' s daim ntawv thov tshuaj tshiab thiab muab kev tshuaj xyuas qhov muaj feem thib. Tabrecta yog thawj FDA pom zoo MET exon 14 dhia hloov pauv metastatic tsis-me me ntawm tes ntsws mob qog nqaij hlav tshwj xeeb kev kho hom phiaj.

Tabrecta yog qhov ncauj xaiv tau ntau me me molecule MET inhibitor uas tuaj yeem tiv thaiv MET phosphorylation tshwm sim los ntawm hepatocyte qhov muaj feem cuam tshuam lossis MET amplification, raws li MET-mediated phosphorylation ntawm downstream signaling protein thiab MET-dependant mob hlwb ua kom loj hlob thiab muaj sia nyob.

Capmatinib yog Ameslikas tsim los ntawm Incyte Corporation. Lub Kaum Ib Hlis 2009, Novartis thiab Incyte tau kos npe rau daim ntawv pom zoo tshwj xeeb thoob ntiaj teb rau Capmatinib. Daim ntawv cog lus tseem hais txog kev ua lag luam ua lag luam ntawm lucotinib hauv thaj chaw uas tsis yog Tebchaws Meskas. Incyte tshwj tseg cov kev txhawb nqa dav hauv Tebchaws Meskas. Capmatinib muaj txoj cai thiab koom nrog hauv kev tsim kho hauv ntiaj teb ntawm cov kab ke no. Lub Kaum Hlis 2014, Novartis thiab Squibb tau kos npe rau kev soj ntsuam theem I / II kev koom tes los soj ntsuam peb lub qauv sib xyaw ntawm Novartis (seritinib, Capmatinib thiab nazatinib) ua ke nrog BMS ntawm Nivolumab Qhov kev nyab xeeb, kam rau siab thiab ua kom tau txais txiaj ntsig ntawm tes. mob ntsws. Nyob rau Lub Ib Hlis 2015, Novartis tau pib qhov Kev Ntsuam Xyuas Theem II los tshawb xyuas qhov kev ua haujlwm ntawm kev ua haujlwm ntawm Capmatinib txuas nrog Binimetinib, Alpelisib thiab ceritinib hauv cov neeg mob uas tsis yog mob me me hauv lub ntsws mob ntsws.

Yaodu cov ntaub ntawv qhia tau hais tias Capmatinib tam sim no nyob rau Theem II kev soj ntsuam kev kho mob rau kev kho tus mob glioblastoma, mob siab mob cancer, malanant melanoma, Theem I / II soj ntsuam rau kev mob qog nqaij hlav cancer, mob taub hau thiab caj dab, thiab Theem I kev soj ntsuam rau kev kho mob qog. Tam sim no tsis muaj kev nce qib hauv cov kev tshawb fawb soj ntsuam ntawm Capmatinib rau kev kho mob ntawm cov qog nqaij hlav hauv hlwb.

Cov ntaub ntawv tseem ceeb

Tabrecta' kev pom zoo yog ua raws cov txiaj ntsig ntawm qhov tseem ceeb multicenter, tsis yog-random, qhib-daim ntawv lo, ntau pawg ntawm theem ob sim ntawm GEOMETRYmono-1. Thawj qhov kawg kev kho mob yog qhov ntsuas kev teb tag nrho (ORR). Cov kev tso npe 97 tau muab faib ua ob pawg, noj tshuaj ib hnub ob zaug, thiab cov txiaj ntsig tau pom tias qhov ua tau zoo yog qhov tseem ceeb, pawg neeg mob uas tsis tau txais kev kho mob (n= 28) thiab cov pab pawg ntawm cov neeg mob uas yav tas los tau txais kev kho mob (n= 69) Lub ORR yog 68% thiab 41%, raws li, thiab qhov nruab nrab ntawm kev kho dua yog 12. 6 hli thiab 9. 7 hli, xwm yeem.

Cov kev kho feem ntau ntsig txog qhov tshwm sim tsis zoo (AE) (qhov tshwm sim ≥ 20%) yog qhov txhawm rau txhawm rau txhav, xeev siab, nkees, ntuav, ua tsis tau pa, thiab tsis qab los.

Muaj 2 lab cov neeg mob ntsws tshiab thoob ntiaj teb txhua lub xyoo, uas NSCLC suav txog 85%. Ze li ntawm 70% ntawm cov neeg mob NSCLC muaj kev hloov caj ces. MET exon 14 hla yog qhov kev lees paub oncogenic tus neeg tsav tsheb, suav txog 3% rau 4% ntawm cov nyuam qhuav mob kuaj mob NSCLC (txog 4 000-5000 tus neeg mob ib xyoos nyob rau hauv Meskas).

Tabrecta' kev pom zoo muab kev cia siab tshiab rau cov neeg mob NSCLC nrog kev hloov no. Tabrecta tuaj yeem raug siv los ua kev kho thawj zaug thiab rau kev kho mob yav dhau los NSCLC cov neeg mob (tsis hais txog ntawm hom kev kho yav dhau los). Cov khoom lag luam yuav tsum tau ntsib cov neeg mob hauv ob peb hnub tom ntej.

Ntau tshaj kaum c-Met tsom tshuaj rau hauv kev tshawb fawb hauv Suav teb

Receptor tyrosine kinase c-Met kuj tseem hu ua hepatocyte qhov zoo tshaj yuav receptor (HGFR). Lub ligand ntawm C-MET yog hepatocyte kev loj hlob tau (HGF). Kev sib xyaw ntawm HGF thiab c-MET tuaj yeem txhawb txoj kev loj hlob ntawm tes, tsiv teb tsaws, muaj kev sib txawv thiab hloov morphological. c-Met cov tshuaj tiv thaiv muaj peev xwm kho kev mob plab, mob raum thiab mob ntsws, thiab tuaj yeem tsim tshwj xeeb rau kev kho mob qog noj ntshav uas tiv taus cov tshuaj tiv thaiv tam sim no. c-MET tau dhau los ua ib qho ntawm cov kev tshawb fawb kub tam sim no hauv thaj tsam mob qog nqaij hlav.

Tom qab nug cov ntaub ntawv Yaodu, raws li lub sijhawm xovxwm, muaj 18 Cov Chav Suav 1 c-Met tshuaj kho mob tseem tab tom ua nyob rau hauv Suav teb, suav txog thaj chaw kho mob qog, mob plawv, thiab lwm yam. ntau tshaj ib lub kaum os xws li Hausen, Hengrui, thiab lwm yam Chaw Pauv Tshuaj.

Thawj echelon: ob qho tshuaj nyob hauv kev tshawb fawb hauv chaw kho mob theem III, uas yog Pudk-HGF thiab Volitinib (Volitinib).

Pudk-HGF: Hepatocyte txoj kev loj hlob kev txhaj tshuaj (PUDK-HGF), tus kws kho mob plasmid tsim los ntawm lub koom haum ntawm Kev Tshawb Fawb thiab Hluav Taws Xob Hluav Taws Xob Tshuaj ntawm Suav Academy ntawm Tub Rog Kev Tshawb Fawb thiab Wuhan Optical Valley Renfu Biomedicine (lub chaw muag khoom ntawm Renfu Pharmaceutical) Nws yog siv los kho cov ceg tawv ischemic heev. Cov kab mob no yog cov khoom siv roj ntsha uas siv cov lus qhia plasmid ua cov cab kuj thiab hepatocyte kev loj hlob los ua cov tshuaj kho cov noob. Txog tam sim no, nws tau ua tiav cov kev tshawb fawb qib II thiab tau pom zoo rau cov kev tshawb fawb qib III.

Volitinib: Ib qho kev xaiv heev c-Met qhov ncauj inhibitor tsim los ntawm Hutchison MediPharma, tshwj xeeb muaj qhov cuam tshuam loj heev ntawm cov qog ua tsis xws li c-Met gene amplification lossis c-Met protein overexpression. Hauv 2011, Hutchison MediPharma tau tso cai AstraZeneca los tsim kev sib xyaw tshuaj' s kev kho mob cancer. Hauv 2012, Hutchison Whampoa xa daim ntawv thov tshuaj rau voritinib ntsiav tshuaj hauv Suav teb, thiab tau txais kev pom zoo hauv kev kuaj mob hauv lub Peb Hlis 2013. Lub Ob Hlis 2017, kev soj ntsuam qib II kawm (NCT 02897479, 20 1 6-504-00CH 1, CTR20 1 6058 1 ) ntawm cov neeg mob hauv cheeb tsam ua ntej lossis mob ntsws ua pa sarcomatoid carcinoma (PSC) nrog MET exon 1 4 hloov tau ua tiav thawj qhov kev kawm hauv Suav Teb Koom nrog pawg. Txoj kev tshawb no ntawm voritinib hauv kev kho papillary hlwv cell carcinoma (ntawm lub ntiaj teb ntsuas) yog nyob rau thaj chaw kho mob III. Nws yog siv rau hauv kev kho mob ntawm txoj hnyuv mob cancer, mob plab, mob ntsws, thiab mob qog nqaij hlav cancer (hauv ntiaj teb thiab Tuam Tshoj) thiab nyob hauv cov chaw kho mob theem II.

Qhov thib ob echelon: 5 tshuaj nyob hauv kev tshawb nrhiav hauv chaw kho mob theem II, uas yog EMB-01, Bozitinib (Bretinib), Ningetinib Tosylate (Ningatinib p-toluenesulfonate), AL-2846, Glumetinib (Gumeti Nepal).

EMB-01: Raws li nws FIT-Ig? Tshuab (Fabs-In-Tandem Immunoglobulin) tau tsim cov tshuaj tiv thaiv bispecific uas tsom cov kabmob loj hlob ntawm cov kabmob receptor EGFR thiab hepatocyte kev loj hlob los ntawm c-Met / HGFR thiab yog npaj los siv rau kev kho mob qog.

Bozitinib (Berritinib): Keeb kwm yog tsim los ntawm yas Bioscience, tom qab ntawd lub tuam txhab spin-off tuam txhab CBT kws tsim kev koom tes nrog koom nrog Beijing Purunao Biotechnology (ib lub chaw tsim khoom ntawm Hengkang Group). , Thiab CBT yog lub luag haujlwm rau kev tsim kho ntawm lwm thaj chaw tshwj tsis yog Suav. Cov kab mob no yog c-Met inhibitor tsom rau qhov kev hloov pauv epithelial-mesenchymal (EMT) thiab npaj rau kev kho mob ntawm cov qog ntshav tsis mob ntsws hauv hlwb (NSCLC), glioma, mob raum cell carcinoma (RCC) thiab hepatocellular carcinoma (HCC) Cov.

Ningetinib Tosylate (Ningetinib p-toluenesulfonate): Ntau hom kev tiv thaiv kab mob tsim los ntawm Guangdong Dongguang, npaj rau kev kho mob qog nqaij hlav, suav nrog mob ntsws, mob plab, mob plab hnyuv, FLT 3 gene hloov pauv-zoo rov ua mob / rov huam dua qub myeloid leukemia 1. Theem IIIB lossis theem IV tsis mob qog nqaij hlav cancer nrog T 790 M hloov pauv tsis zoo tom qab kho EGFR TKI.

AL-2846: Tsim los ntawm Ed Cheng Ningxin thiab Zhengda Tianqing, tam sim no nyob rau hauv chaw kho mob Theem II, tau siv los kho kev mob ntsws tsis muaj kabmob me rau cov ntsws.

Glumetinib: Shanghai lub koom haum ntawm Materia Medica, Suav Academy ntawm Kev Tshawb Fawb thiab Shanghai Lvgu Pharmaceutical Co., Ltd. tau xa daim ntawv thov kev sim tshuaj (Tshuaj lom neeg Tshuaj 1) mus rau Tuam Tshoj Khoom Noj thiab Tshuaj, tam sim no nyob rau Ntu II soj ntsuam kev soj ntsuam rau kev kho mob ntawm cov tsis mob me me cell mob cancer

Qhov thib peb echelon: 10 tshuaj nyob rau hauv kev tshawb nrhiav hauv chav kho mob I, hu ua QBH-196, Kanitinib (Boxitinib), Boxitinib Hydrochloride (CM), CM-118, GST-HG 161, HS-10241, HQP 8361 (kaitai ketone amine), LMV-12 (HE 003), SPH 3348, SHR-A 1403.

SHR-A 1403: SHR-A 1403 tsim los ntawm Jiangsu Hengrui Tshuaj Co., Ltd. yog tus neeg ua haujlwm tiv thaiv kab mob kev loj hlob kabmob receptor (HGFR / c-Met) monoclonal antibody tsim los ntawm tshuaj lom neeg txuas ntawm microtubule inhibitors. Cov tshuaj tiv thaiv kab mob tuaj yeem khi tus c-Met rau ntawm cov qog nqaij hlav, endocytose cov tshuaj tiv thaiv kab mob-tshuaj sib xyaw ua ke rau cov qog ntshav, thiab tso cov tshuaj molecule me me tom qab lysosome degrades, uas tuaj yeem tua cov qog nqaij hlav. Lub Ob Hlis 2019, theem kev soj ntsuam Kuv kawm (NCT 03856541) hauv cov neeg mob uas muaj lub qog ua haujlwm nyuaj pib nyob hauv Suav teb.

HS-10241: c-Met inhibitor tsim los ntawm Jiangsu Howson. Tam sim no nws nyob rau hauv chaw kho mob theem I hauv Suav teb thiab siv los kho cov qog ua kom zoo (mob qog, mob ntsws, thiab mob plab).