Amgen Submits New Drug Application to FDA for Sotorasib (AMG 510), a First-in-Class KRASG12C Inhibitor, for Previously Treated Advanced NSCLC

On December 16, Amgen announced that it had submitted a marketing application to the U.S. Food and Drug Administration (FDA) for sotorasib (AMG 510), a KRAS G12C inhibitor, for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring KRAS G12C mutations in patients who have received at least one prior systemic therapy.

Benefiting from the Breakthrough Therapy designation, sotorasib’s New Drug Application will receive accelerated approval from the FDA, and the FDA will evaluate sotorasib through the Real-Time Oncology Review (RTOR) program. Projects included in the RTOR program may take only a few weeks to gain approval from the completion of data submission.

This marketing application submission is based on the results of the Phase I/II clinical study codenamed CodeBreaK 100. In this study, sotorasib treatment demonstrated durable antitumor activity and positive clinical benefits. Among 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 results position sotorasib as a promising new treatment option for NSCLC, potentially offering enhanced efficacy when combined with other antitumor agents. The findings 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 the past 40 years. 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 comprehensive clinical dataset encompassing 13 tumor types and more than 600 patients.

Source: PharmCube NextPharma

Amgen is ahead of its competitors in bringing KRAS inhibitors to market. Mirati, following closely behind, announced preliminary data on MRTX849 for the treatment of NSCLC in October this year and plans to submit a marketing application in the second half of next year. The timeline suggests that Amgen’s Sotorasib may receive FDA approval around the time Mirati submits its marketing application for MRTX849 next year.

In China, Amgen has submitted two clinical trial applications to the NMPA since March this year, both of which have been approved for clinical trials.

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 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 frequencies of KRAS G12C mutations are also observed in pancreatic cancer (<1%), cervical cancer (<1%), bladder cancer (<1%), and gastric cancer (<1%).