Amgen's Lumykras (sotorasib) Pom zoo los ntawm EU: Kev Ua Tau Zoo Hauv Kev Kho Mob Ntawm KRAS G12C Mutant Mob ntsws Cancer!

Amgen (AMGEN) tsis ntev los no tshaj tawm tias European Commission (EC) tau tso cai pom zoo rau lub hom phiaj tshuaj tiv thaiv kab mob Lumykras (sotorasib): cov tshuaj yog thawj-hauv-chav KRASG12C inhibitor rau kev kho mob yav dhau los tau txais cov neeg laus cov neeg laus uas tsis yog- me me mob ntsws cancer (NSCLC) harboring KRAS G12C kev hloov nrog cov kab mob kev loj hlob tom qab tsawg kawg yog ib qho kev kho mob. Kev pom zoo txuas ntxiv rau qhov ntsuas no yuav muaj raws li kev txheeb xyuas thiab kev piav qhia ntawm cov txiaj ntsig kho mob hauv kev kuaj mob uas tau lees paub.

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.

To date, sotorasib has been approved in 35 countries around the world. In China, sotorasib was listed as a "breakthrough therapy" by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) in February 2021. This designation is for the treatment of patients with locally advanced or metastatic NSCLC harboring a KRAS G12C mutation who have received at least one prior systemic therapy.

Notably, Lumakras is the first KRAS-targeted therapy approved after nearly 40 years of research, and the first and only target approved for the treatment of patients with locally advanced or metastatic NSCLC harboring a KRAS G12C mutation to therapy. NSCLC is the most common type of lung cancer, accounting for approximately 84% of the 2.2 million newly diagnosed lung cancer cases worldwide each year. KRAS mutation, the most common driver mutation in NSCLC, is now a "druggable" target. KRAS mutations account for about 25% of NSCLC mutations; among them, KRAS G12C is the most common type of KRAS mutation in NSCLC. About 13% of non-squamous NSCLC patients carry the KRAS G12C mutation.

Kev pom zoo EU yog ua raws li cov txiaj ntsig zoo los ntawm pawg neeg mob ntawm cov neeg mob uas muaj NSCLC qib siab hauv Phase 2 CodeBreaK 100 txoj kev kawm. Txoj kev tshawb no yog qhov kev sim loj tshaj plaws rau hnub tim hauv cov neeg mob nrog KRAS G12C kev hloov pauv. Cov ntaub ntawv los ntawm ib pawg ntawm 124 tus neeg mob nrog KRAS G12C kev hloov pauv-zoo NSCLC uas nws tus kab mob tau nce zuj zus tom qab kev tiv thaiv kab mob thiab / lossis tshuaj siv tshuaj kho mob pom tias Lumakras tau txais txiaj ntsig zoo thiab zam tau zoo.

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%).

Chemical structural formula of sotorasib (AMG510)

Ib qho ntawm thawj cov kab mob oncogenes tau pom, KRAS tau hloov pauv hauv kwv yees li ib feem peb ntawm tib neeg cov qog nqaij hlav thiab yog ib lub hom phiaj zoo tshaj plaws hauv kev txhim kho tshuaj oncology. Txawm li cas los xij, hmoov tsis, txawm tias nws qhov kev cia siab, KRAS yuav luag tsis tuaj yeem kov yeej tau ntev. Qhov no yog vim lub fact tias cov protein yog ib tug featureless, ze li ntawm spherical qauv uas tsis pom tseeb losis tswvyim dabtsi qhov chaw. Nws yog ib qho nyuaj rau synthesize lub hom phiaj khi thiab inhibitory active compounds. Qhov no kuj ua rau KRAS synonymous nrog"undruggable" cov hom phiaj hauv kev tsim kho tshuaj oncology.

Sotorasib (AMG 510) is one of the first small-molecule inhibitors that successfully target KRAS and enter human clinical development. It can target and inhibit the KRAS protein carrying the G12C mutation. Sotorasib specifically and irreversibly inhibits the pro-proliferative activity of G12C mutant KRAS protein by locking it in an inactive GDP-bound state.

Los ntawm kev tsim cov tshuaj sotorasib, Amgen tau ua tiav ib qho nyuaj tshaj plaws hauv kev tshawb fawb mob qog noj ntshav hauv 40 xyoo dhau los. sotorasib yog thawj KRASG12C inhibitor nkag mus rau hauv tsev kho mob. Tam sim no, Amgen tab tom ua qhov loj tshaj plaws thiab dav thoob ntiaj teb KRASG12C inhibitor txoj kev txhim kho ntawm qhov tsis sib xws, tshawb nrhiav ntau dua 10 cov tshuaj sib xyaw ua ke nrog cov chaw kuaj mob hla tsib lub tebchaws. Txog niaj hnub no, Lumakras / Lumykras tau kho ntau dua 3,000 tus neeg mob thoob ntiaj teb los ntawm kev kho mob thiab kev siv lag luam.