Amgenning Lumykras (sotorasib) Yevropa Ittifoqi tomonidan tasdiqlangan: KRAS G12C mutant o'pka saratonini davolashda kuchli samaradorlik!

Amgen (AMGEN) recently announced that the European Commission (EC) has granted conditional approval to the targeted anticancer drug Lumykras (sotorasib): the drug is a first-in-class KRASG12C inhibitor for the treatment of previously received Adult patients with advanced non-small cell lung cancer (NSCLC) harboring a KRAS G12C mutation with disease progression after at least one systemic therapy. Continued approval for this indication will be contingent upon verification and description of clinical benefit in confirmatory clinical trials.

It is worth mentioning that Lumykras is the first targeted therapy in the EU for KRAS G12C mutation, which is one of the most common biomarkers in NSCLC. It is estimated that approximately 13-15% of European NSCLC patients carry the KRAS G12C mutation.

Sotorasib, the first KRAS G12C inhibitor to enter clinical development, was approved by the U.S. FDA in May 2021 (trade name Lumakras) for the treatment of patients who have received at least one prior systemic therapy confirmed by an FDA-approved assay Adult patients with KRAS G12C-mutated, locally advanced or metastatic NSCLC. In clinical trials, sotorasib treatment demonstrated rapid, deep, and durable anticancer activity with a positive benefit-risk profile.

Bugungi kunga qadar sotorasib dunyoning 35 davlatida tasdiqlangan. Xitoyda sotorasib"reaktif terapiya" 2021-yil fevral oyida Milliy tibbiy mahsulotlar boshqarmasi (NMPA) Dori vositalarini baholash markazi (CDE) tomonidan 2021-yilda. .

Shunisi e'tiborga loyiqki, Lumakras 40 yillik tadqiqotlardan so'ng tasdiqlangan birinchi KRAS maqsadli terapiyasi bo'lib, terapiya uchun KRAS G12C mutatsiyasiga ega bo'lgan mahalliy rivojlangan yoki metastatik NSCLC bilan og'rigan bemorlarni davolash uchun tasdiqlangan birinchi va yagona maqsaddir. NSCLC o'pka saratonining eng keng tarqalgan turi bo'lib, har yili dunyo bo'ylab yangi tashxis qo'yilgan 2,2 million o'pka saratoni holatlarining taxminan 84% ni tashkil qiladi. KRAS mutatsiyasi, NSCLCda eng keng tarqalgan haydovchi mutatsiyasi, endi"dori bilan ta'minlangan" maqsad. KRAS mutatsiyalari NSCLC mutatsiyalarining taxminan 25% ni tashkil qiladi; ular orasida KRAS G12C NSCLCda KRAS mutatsiyasining eng keng tarqalgan turi hisoblanadi. Skuamöz bo'lmagan NSCLC bemorlarning taxminan 13% KRAS G12C mutatsiyasiga ega.

The EU approval is based on positive results from a cohort of patients with advanced NSCLC in the Phase 2 CodeBreaK 100 study. The study is the largest clinical trial to date in a patient population with KRAS G12C mutations. Data from a cohort of 124 patients with KRAS G12C mutation-positive NSCLC whose disease had progressed following immunotherapy and/or chemotherapy showed that Lumakras was well efficacious and well tolerated.

In this cohort, patients treated with Lumakras 960 mg orally once daily had an objective response rate (ORR) of 37.1% (95%CI: 28.6-46.2), a median duration of response (DoR) of 11.1 months, and a disease control rate ( DCR) was 80.6%, and the median overall survival (mOS) was 12.5 months. The most common adverse reactions were diarrhea (34%), nausea (25%), and fatigue (21%). The most common serious (grade ≥3) adverse reactions were increased alanine aminotransferase (ALT; 5%), increased aspartate aminotransferase (AST; 4%), and diarrhea (4%).

Sotorasibning kimyoviy tuzilish formulasi (AMG510)

Birinchi kashf etilgan onkogenlardan biri bo'lgan KRAS inson o'smalarining to'rtdan birida mutatsiyaga uchragan va onkologik dori-darmonlarni ishlab chiqishda eng aniq belgilangan maqsadlardan biridir. Biroq, afsuski, istiqbolli istiqbollariga qaramay, KRASni uzoq vaqt davomida engish deyarli mumkin emas. Buning sababi shundaki, oqsil aniq bog'lanish joyiga ega bo'lmagan deyarli sharsimon tuzilishga ega. Maqsadli bog'lovchi va inhibitiv faol birikmalarni sintez qilish qiyin. Bu ham KRASni"unruggable" bilan sinonim qiladi; onkologiya dori vositalarini ishlab chiqish sohasidagi maqsadlar.

Sotorasib (AMG 510) KRASni muvaffaqiyatli nishonga olgan va insonning klinik rivojlanishiga kirgan birinchi kichik molekulali ingibitorlardan biridir. U G12C mutatsiyasini tashuvchi KRAS oqsilini nishonga olishi va inhibe qilishi mumkin. Sotorasib G12C mutant KRAS oqsilining proliferativ faolligini, uni faol bo'lmagan YaIM bilan bog'langan holatda qulflash orqali maxsus va qaytarilmas tarzda inhibe qiladi.

Sotorasibni ishlab chiqish orqali Amgen so'nggi 40 yil ichida saraton kasalligini tadqiq qilishdagi eng qiyin muammolardan birini o'z zimmasiga oldi. sotorasib klinikaga kirgan birinchi KRASG12C inhibitori hisoblanadi. Hozirgi vaqtda Amgen besh qit'ani qamrab olgan klinik sinov maydonchalari bilan 10 dan ortiq dori kombinatsiyalarini o'rganib, eng katta va eng keng global KRASG12C inhibitörlerini ishlab chiqish dasturini misli ko'rilmagan sur'atda rivojlantirmoqda. Bugungi kunga qadar Lumakras/Lumykras butun dunyo bo'ylab klinik rivojlanish dasturlari va tijorat maqsadlarida foydalanish orqali 3000 dan ortiq bemorlarni davolagan.