Inhibitor Nerlynx (neratinib) Phase 2 Clinical Prolonged Progression-free Survival!

Beihai Kangcheng tus khub Puma Biotechnology tsis ntev los no tshaj tawm cov txiaj ntsig ntawm Theem 2 INSIghT sim Nerlynx (neratinib txiv neej) pab pawg kho mob ntawm 26th Lub Rooj Sib Tham Txhua Xyoo ntawm American Society of Neuro-Oncology (SNO) hauv 2021. Saib daim ntawv tshaj tawm lub rooj sib tham kom paub meej: Cov txiaj ntsig ua ntej ntawm neratinib caj npab nyob rau hauv Kev Ntsuas Tus Kheej Kev Sib Tham ntawm Innovative Glioblastoma Therapy (INSIGhT): ib theem II platform sim siv Bayesian adaptive randomization (INSIGhT) Cov txiaj ntsig ua ntej ntawm pawg neratinib: Theem 2 platform sim siv Bayesian adaptive randomization).

Qhov kev sim INSIGhT yog ntau qhov chaw, tus neeg tshawb nrhiav-pib theem 2 kev tshuaj ntsuam kev hloov kho platform mus sib hais. Cov neeg mob uas tau cuv npe kawm yog cov neeg mob tshiab uas tau kuaj pom tsis tau cov tshuaj glioblastoma uas tsis zoo rau IDH R132H kev hloov pauv thiab muaj cov ntaub ntawv genomic muaj Grouped hauv biomarkers. Txhua tus neeg mob tau txais kev kho hluav taws xob thiab temozolomide, thiab tom qab ntawd cov neeg mob tau muab faib ua adjuvant temozolomide kev kho mob thiab kev kho mob nrog kev sim tshuaj (neratinib).

Thaum INSIghT tau tsim tawm, 3 pawg sim tau sim tib lub sijhawm, thiab txhua pab pawg sim tau muaj cov phiaj xwm genomic biomarker. Thawj randomization yog sib npaug ntawm cov pab pawg. Raws li qhov kev sim ua tiav, kev kwv yees Bayesian yog siv los ua biomarker tshwj xeeb qhov yuav tshwm sim ntawm kev kho mob ntawm kev muaj sia nyob tsis muaj sia (PFS). Qhov tshwm sim ntawm tus neeg mob randomization yog hloov kho raws li cov txiaj ntsig sib sau.

Yog tias qhov kev kho mob muaj qhov tshwm sim tsawg ntawm kev cuam tshuam rau tag nrho cov ciaj sia taus (OS), pawg kho mob raug tso cai thim tawm. Thawj qhov kawg ntawm INSIGhT yog kev ciaj sia tag nrho (OS). Progression-free survival (PFS) kev tsom xam tau siv los cuam tshuam rau randomization. Rau cov pab pawg neratinib ntawm qhov kev sim, cov neeg mob tau noj 240 mg ntawm neratinib txhua hnub raws li kev kho mob monotherapy thiab yuam loperamide los tiv thaiv raws plab.

Rau pawg neratinib ntawm qhov kev sim, muaj 149 tus neeg mob nyob rau hauv cov neeg mob siab rau-kho, suav nrog 81 tus neeg mob hauv pawg neratinib thiab 68 tus neeg mob hauv pawg tswj hwm. Rau cov pej xeem npaj-rau-kho, PFS ntawm pawg neratinib tsis tau ncua ntev piv nrog cov pab pawg tswj hwm (piv txwv li PFS: 6.0 lub hlis vs 4.7 lub hlis; HR=0.75; p=0.12, kev xeem ntawv teev npe). Cov pab pawg neratinib tau muab piv nrog pawg tswj hwm. Tsis muaj kev txhim kho tseem ceeb ntawm OS (qhov nruab nrab OS: 13.8 hli vs 14.7 hli; HR1.01; p=0.75).

Txawm li cas los xij, rau cov neeg mob uas muaj EGFR txoj hauv kev ua kom (txhais tau tias yog EGFR amplification lossis kev hloov pauv), PFS ntawm pawg neratinib tau ntev dua li ntawm pawg tswj hwm (piv txwv li PFS: 6.3 hli vs 4.6 hli; HR=0.58; p=0.04, Log-rank test); pawg neratinib tsis muaj kev txhim kho tseem ceeb hauv OS piv nrog pawg tswj hwm ( nruab nrab OS: 14.4 hli vs 15.3 hli; HR=0.97; p=0.94).

Hauv qhov kev sim no, neratinib feem ntau tau txais txiaj ntsig zoo thiab nws cov tshuaj lom tau zoo ib yam li tau piav qhia yav dhau los. Ntawm 81 tus neeg mob kho nrog neratinib, 6 tus neeg mob (7.4%) muaj raws li qib 3 raws plab, thiab qib 4 tsis muaj raws plab. Tsis muaj cov cim tshiab ntawm toxicity tau pom hauv qhov kev sim.

Alan H. Auerbach, CEO thiab Thawj Tswj Hwm ntawm Puma, hais tias:" Nov yog thawj cov ntaub ntawv los ua pov thawj tias neratinib muaj txiaj ntsig zoo rau glioblastoma nrog EGFR amplification lossis kev hloov pauv. Txawm hais tias peb tsis npaj siab yuav txuas ntxiv txhim kho neratinib hauv qhov ntsuas no. Kev tshawb fawb soj ntsuam, tab sis peb tab tom ntsuam xyuas lub peev xwm ntawm kev tsim cov txheej txheem thaub qab HKI-357 rau kev kho mob ntawm glioblastoma, uas qhia tau hais tias zoo dua los tiv thaiv EGFR ua ntej kev sim tshuaj."

Nerlynx-neratinibchemical qauv

Nerlynx (neratinib) yog lub qhov ncauj, muaj zog, tsis muaj zog tyrosine kinase inhibitor (TKI) uas inhibits qog loj hlob thiab qog loj hlob los ntawm kev thaiv cov yias-HER tsev neeg (HER1, HER2, HER4) thiab downstream signaling pathways. Hloov. Cov tshuaj' cov txheej txheem ntawm kev ua yog txawv ntawm Roche Herceptin (trastuzumab) thiab cov tshuaj kho mob cancer mis tshiab Perjeta (Pertuzumab). Ob lub tom kawg yog cov tshuaj monoclonal antibody uas tsom HER2 receptor nyob rau saum npoo ntawm HER2-zoo mob qog noj ntshav. lub cev.

Nws tsim nyog hais tias Nerlynx yog thawj qhov kev kho mob hnyav rau HER2+ mob qog noj ntshav thaum ntxov pom zoo los ntawm Tebchaws Meskas thiab European Union. Cov tshuaj tau pom zoo hauv Tebchaws Meskas thiab European Union thaum Lub Xya Hli 2017 thiab Cuaj Hlis 2018, raws li. Kev kho mob hnyav ntxiv rau HER2+ cov neeg mob qog noj ntshav thaum ntxov uas ua tiav trastuzumab adjuvant therapy tom qab ua haujlwm.

Thaum Lub Ib Hlis 2018, Beihai Kangcheng thiab Puma Biotechnology tau kos npe rau daim ntawv tso cai tshwj xeeb rau kev txhim kho thiab kev lag luam ntawm Nerlynx hauv thaj av loj Tuam Tshoj (Mainland, Taiwan, Hong Kong, Macau). Thaum lub Plaub Hlis 2020, Nerlynx (Suav lub npe lag luam: He Li' ib lub npe: Nelatinib maleate ntsiav tshuaj) tau pom zoo los ntawm National Medical Products Administration (NMPA): nws yog siv los kho HER2-zoo thaum ntxov mob qog noj ntshav. (eBC) cov neeg mob. Intensive adjuvant therapy tom qab kev kho mob nrog trastuzumab. Qhov kev pom zoo no ua rau cov neeg mob eBC nyob hauv Suav teb loj tuaj yeem muaj kev kho qhov ncauj rau thawj zaug.