Amgen’s Sotorasib Receives FDA Priority Review for KRAS G12C-Mutated Non-Small Cell Lung Cancer

February 17, 2021 News /BioValleyBIOON/ -- Amgen recently announced that the U.S. Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for the targeted anti-cancer drug sotorasib (AMG 510) and granted it Priority Review. Sotorasib is a KRAS G12C inhibitor indicated for the treatment of patients who have previously received at least one systemic therapy.FDAPatients with locally advanced or metastatic non-small cell lung cancer (NSCLC) confirmed to harbor KRAS G12C mutations by an approved diagnostic test. Under priority review, the Prescription Drug User Fee Act (PDUFA) target date for the sotorasib New Drug Application (NDA) is August 16, 2021, which is four months shorter than the standard review cycle.

In early December 2020,FDAGranted sotorasib Breakthrough Therapy Designation (BTD) and real-timeTumorReview of Qualification for Breakthrough Therapy Designation (RTOR). At the end of January 2021, sotorasib was granted Breakthrough Therapy Designation by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA). This marked Amgen’s first application for Breakthrough Therapy Designation in China, and the first such application since its strategic collaboration with BeiGene.

Amgen to the United States on December 16, 2020FDAThe New Drug Application (NDA) for sotorasib has been submitted. Currently, the agency is evaluating this NDA under the Real-Time Oncology Review (RTOR) pilot program. The RTOR program aims to explore a more efficient review process to ensure early patient access to safe and effective therapies. In December 2020, Amgen submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA). Additionally, in January 2021, Amgen submitted MAAs to Australia, Brazil, Canada, and the United Kingdom.

Sotorasib is the first KRAS G12C inhibitor to enter clinical development, and it now has the potential to become the first targeted therapy approved for treating patients with advanced NSCLC harboring KRAS G12C mutations.. In the United States, approximately 13% of patients with non-small cell lung cancer (NSCLC) harbor the KRAS G12C mutation, facing significant unmet medical needs

The marketing application for sotorasib is based on the positive results from the advanced non-small cell lung cancer (NSCLC) patient cohort in the Phase II CodeBreaK 100 study, involving patients who had previously progressed after chemotherapy and/or immunotherapy. The full results of this study were presented online at the 21st World Conference on Lung Cancer (WCLC) in 2020.Conferencepublished, data showed that: in patients with advanced NSCLC harboring KRAS G12C mutations who had previously progressed on chemotherapy and/or PD-1/PD-L1 immunotherapy, sotorasib demonstrated durable antitumor activity and a favorable benefit-risk profile: the confirmed objective response rate (ORR) was 37.1%, the disease control rate (DCR) was 80.6%, the median duration of response (DOR) was 10 months, and the median progression-free survival (PFS) was 6.8 months. Exploratory analyses showed that across a range ofBiomarkerEncouraging Response to Sotorasib Observed in SubgroupsTumorresponses, including patients with negative or low PD-L1 expression levels and those with STK11 mutations. This co-mutation is associated with poor prognosis in NSCLC patients receiving checkpoint inhibitors and chemotherapy.

Currently, Amgen is conducting a global Phase 3 randomized, active-controlled study (CodeBreaK 200) comparing sotorasib with docetaxel chemotherapy in patients with KRAS G12C-mutated non-small cell lung cancer (NSCLC).

Sotorasib (AMG510) Chemical Structure (Image source: selleck.cn)

KRAS G12C is the most common KRAS mutation in NSCLC. In the United States, approximately 13% of patients with NSCLC adenocarcinoma harbor the KRAS G12C mutation, and about 25,000 new patients are diagnosed annually with KRAS G12C-mutant NSCLC. For patients with KRAS G12C-mutant NSCLC who have failed first-line therapy, treatment options are very limited, resulting in a significant unmet medical need. Current therapies for second-line treatment of KRAS G12C-mutant NSCLC show suboptimal efficacy, with response rates ranging from 9% to 18% and a median progression-free survival (PFS) of only approximately 4 months.

KRAS is one of the first oncogenes discovered, with mutations present in approximately one-quarter of human tumors, making it one of the most well-defined targets in oncology drug development. Unfortunately, despite its promising potential, KRAS has long been considered nearly undruggable due to its featureless, near-spherical structure lacking obvious binding sites, which makes it challenging to develop compounds that can specifically bind and inhibit its activity. Currently, KRAS has become synonymous with “undruggable” targets in the field of cancer drug research and development.

Sotorasib (AMG 510) is one of the first small-molecule inhibitors to successfully target KRAS and enter human clinical development, specifically targeting KRAS proteins harboring the G12C mutation. Sotorasib specifically and irreversibly inhibits the pro-proliferative activity of G12C-mutant KRAS by locking the protein in an inactive GDP-bound state.

By developing sotorasib, Amgen has taken on one of the most formidable challenges in cancer research over the past 40 years. Sotorasib is the first KRAS G12C inhibitor to enter clinical development, and it is currently being studied in CodeBreaK, the most extensive clinical program to date, which is exploring 10 drug combinations across four continents. In just over two years, the CodeBreaK program has also generated the most comprehensive clinical dataset, covering 13TumorA study was conducted on more than 600 patients of this type. (Bioon.com)

Original source:FDA Grants Sotorasib Priority Review Designation For The Treatment Of Patients With KRAS G12C-Mutated Locally Advanced Or Metastatic Non-Small Cell Lung Cancer