Amgen's KRAS Inhibitor AMG 510 (Sotorasib) Granted Breakthrough Therapy Designation by CDE for NSCLC

Source: PharmCube Info

On January 12, the CDE website announced that Amgen’s investigational new drug application for the KRAS G12C inhibitor sotorasib (AMG 510) was proposed by the Center for Drug Evaluation (CDE) for inclusion in the Breakthrough Therapy Designation program. The intended indication in China is for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring KRAS p.G12C mutations who have received at least one prior systemic therapy.

Results from the Phase I/II CodeBreaK 100 clinical trial demonstrated that in patients with KRAS G12C-mutated non-small cell lung cancer (NSCLC) who had experienced disease progression following prior chemotherapy and/or immunotherapy, sotorasib achieved an objective response rate (ORR) of 32.2% and a disease control rate (DCR) of 88.1%, with a median progression-free survival (PFS) of 6.3 months. The study also indicated that monotherapy with sotorasib led to tumor shrinkage in some patients. These findings position sotorasib as a promising new treatment option for NSCLC, with potential for enhanced efficacy when combined with other antineoplastic agents. The results were presented at the 2020 World Conference on Lung Cancer (WCLC), organized by the International Association for the Study of Lung Cancer (IASLC) in January 2021.

Amgen’s development of KRAS G12C mutation inhibitors represents one of the most formidable challenges in human medicine over the past four decades. Sotorasib is the first product to enter clinical development and is currently undergoing extensive clinical studies. The development program spans 10 countries and regions across four continents. In just over two years, the sotorasib clinical program has established a robust clinical dataset encompassing 13 tumor types and more than 600 patients.

Source: PharmaCube NextPharma

KRAS mutations occur in approximately 25% of cancer cases, predominantly in lung cancer, pancreatic cancer, and colorectal cancer, and are associated with a very poor disease prognosis. Among these, the KRAS G12C mutation is one of the most common KRAS mutations, specifically referring to the substitution of glycine by cysteine at position 12 of the KRAS protein. This mutation is present in ~13% of lung adenocarcinomas, ~3% of colorectal cancers, ~2% of uterine cancers, and ~1% of mesotheliomas. Low proportions of KRAS G12C mutations are also observed in pancreatic cancer (<1%), cervical cancer (<1%), bladder cancer (<1%), and gastric cancer (<1%).