2023 yil yanvar: Adagrasib (Krazati, Mirati Therapeutics, Inc.), RAS GTPase oilasi inhibitori, FDA tomonidan tasdiqlangan test bilan aniqlangan KRAS G12C mutatsiyaga uchragan mahalliy rivojlangan yoki metastatik kichik hujayrali bo'lmagan o'pka saratoni (NSCLC) bo'lgan kattalar bemorlari uchun Oziq-ovqat va farmatsevtika idorasi (FDA) tomonidan tezlashtirilgan ruxsat oldi. kamida bir marta tizimli terapiya olganlar.
Krazati uchun qo'shimcha diagnostika sifatida FDA qo'shimcha ravishda QIAGEN therascreen KRAS RGQ PCR to'plamini (to'qima) va Agilent Resolution ctDx FIRST tahlilini (plazma) tasdiqladi. Plazma namunasida mutatsiya belgilari bo'lmasa, o'simta to'qimasini tekshirish kerak.
The KRYSTAL-1 klinik tadqiqotlar (NCT03785249), which involved patients with locally advanced or metastatic NSCLC with KRAS G12C mutations, served as the foundation for the approval. Efficacy was assessed in 112 individuals whose illness had advanced during or after receiving immune checkpoint inhibitors and platinum-based chemotherapy, either concurrently or sequentially. Patients got adagrasib 600 mg twice daily until their condition progressed or the side effects became intolerable.
Samaradorlik natijalarining asosiy o'lchovlari ko'r-ko'rona mustaqil markaziy ko'rib chiqish (DOR) tomonidan baholangan RECIST 1.1 ga muvofiq javob muddati va tasdiqlangan ob'ektiv javob darajasi (ORR) edi. O'rtacha DOR 8.5 oy (95% CI: 6.2, 13.8) va ORR 43% (95% CI: 34%, 53%) edi.
Diareya, ko'ngil aynishi, charchoq, qusish, mushak-skelet tizimining og'rig'i, gepatotoksisite, buyrak etishmovchiligi, nafas qisilishi, shish, ishtahaning pasayishi, yo'tal, pnevmoniya, disorientatsiya, ich qotishi, qorin og'rig'i va QTc intervalining uzayishi eng tez-tez uchraydigan nojo'ya ta'sirlar edi. Limfotsitlarning kamayishi, aspartat aminotransferaza, natriyning ko'payishi, natriy miqdorining pasayishi, gemoglobinning pasayishi, kreatininning ko'payishi, albuminning pasayishi, alanin aminotransferazasining ko'payishi, lipazaning ko'payishi, trombotsitlarning kamayishi, magniyning pasayishi va kaliyning kamayishi eng ko'p uchraydigan laboratoriya anormalliklari (20%).
Adagrasib tabletkalarni og'iz orqali kuniga ikki marta 600 mg dozada holat kuchayguncha yoki chidab bo'lmas toksiklik paydo bo'lguncha qabul qilish kerak.
