Lumakras (Sotorasib) Demonstrates Clinically Meaningful Activity in Heavily Pretreated KRAS G12C-Mutated Advanced Pancreatic Cancer with 84% Disease Control Rate
Feb 16, 2022 01:51
CST Updated
01:51
Amgen
Developer of Treatment Drugs for Serious Diseases
News on February 15, 2022 /BioValleyBIOON/ -- Amgen recently announced the efficacy and safety data of the targeted anticancer drug Lumakras (sotorasib) in treating patients with KRAS G12C-mutated advanced pancreatic cancer from the Phase 1/2 CodeBreaK 100 study. The data showed that Lumakras demonstrated encouraging and clinically meaningful anti-TumorActivity and has a positive benefit-risk profile.
These data come from 38 casesPreviously received multiple treatment regimens (heavily pre-treated)Patients with advanced pancreatic cancer, nearly 80% of patients received Lumakras as a third-line or later treatment. The results showed,The centrally confirmed objective response rate (ORR) was 21%, and the disease control rate (DCR) was 84%.Among 38 patients, 8 achieved partial response (PR) according to blinded independent central review (BICR). Two of the 8 PR patients remain in response. As of the data cutoff date (November 1, 2021), the median follow-up was 16.8 months.The median duration of response (DOR) was 5.7 months, the median progression-free survival (PFS) was 4 months, and the median overall survival (OS) was nearly 7 months.No new safety signals were identified in the study. Treatment-related adverse events (TRAEs) of any grade occurred in 16 patients (42%), with diarrhea (5%) and fatigue (5%) being the most common grade 3 TRAEs. No fatal or treatment-discontinuation TRAEs occurred.
Pancreatic cancer is a highly lethal malignancyTumor. It is the fourth leading cause of cancer-related deaths in American men and women, with a 5-year survival rate of approximately 10%. There is a significant unmet medical need for patients with advanced pancreatic cancer that has progressed after first-line treatment, in the United States.FDAThe approved second-line therapy provides an overall survival of approximately 6 months, with an overall response rate (ORR) of 16%. After the progression of first- and second-line chemotherapy, no therapy has demonstrated a survival benefit. Despite advances in treatment, improvements in pancreatic cancer remain limited.DiagnosisAnd there has been little progress in treatment.
It is estimated thatApproximately 90% of pancreatic cancer patients carry KRAS mutations, with KRAS G12C accounting for about 1-2% of these mutations.. Associate Professor at Duke University School of Medicine, GastrointestinalTumorExpert John Strickler stated: "After decades of research, the survival benefits currently provided to pancreatic cancer patients are limited, indicating an urgent need for new, safe, and effective treatment options. In evaluating the efficacy and safety of KRASG12C inhibitors in heavily pre-treated advanced pancreatic cancer...Big DataIn the centralized analysis, Lumakras achieved a 21% centrally confirmed response rate and an 84% disease control rate. This is clinically meaningful for patients, as there is no established standard therapy once these patients progress to third-line treatment."
Lumakras is a KRASG12C inhibitor that received U.S. FDA approval in May 2021 for the treatment of patients who have previously received at least one systemic therapy.FDAApproved testing methods confirm the presence of KRAS G12C mutations in adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC).
Notably, Lumakras is the first KRAS-targeted therapy approved after nearly 40 years of research, and it is the first and only targeted therapy approved for treating patients with locally advanced or metastatic NSCLC carrying the KRAS G12C mutation. Globally, there are new cases each year.Diagnosis2.2 million lung cancer cases, with NSCLC accounting for approximately 84%. KRAS mutations account for about 25% of NSCLC mutations; among these, KRAS G12C is one of the most common driver mutations in NSCLC and has now become a "druggable" target. In the United States, approximately 13% of non-squamous NSCLC patients carry the KRAS G12C mutation.
Lumakras's active pharmaceutical ingredient is sotorasib, which is the first KRAS G12C inhibitor to enter clinical development. In early December 2020, the United StatesFDAGranted sotorasib Breakthrough Therapy Designation (BTD) and Real-TimeTumorStudy Review Qualification (RTOR). At the end of January 2021, sotorasib was granted Breakthrough Therapy Designation by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) in China. This marks Amgen's first application for "Breakthrough Therapy" designation in China and also the first "Breakthrough Therapy" designation application since its strategic collaboration with BeiGene.
Sotorasib (AMG510) Chemical Structure (Source: selleck.cn)
KRAS is one of the first oncogenes discovered, with mutations present in approximately 1/4 of human tumors, making it one of the most well-defined targets in the field of oncology drug development. Unfortunately, despite its promising potential, KRAS has long been considered nearly impossible to target. This is because the protein has a featureless, nearly spherical structure with no obvious binding sites, making it extremely challenging to synthesize a compound that can specifically bind to and inhibit its activity. This has also made KRAS a...TumorA synonym for "undruggable" targets in the field of 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 inhibiting KRAS proteins with the G12C mutation. Sotorasib specifically and irreversibly inhibits the pro-proliferative activity of the G12C mutant KRAS protein by locking it 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 KRASG12C inhibitor to enter clinical trials and is currently part of an extensive clinical program called CodeBreaK, exploring more than 10 drug combinations across five continents globally. To date, over 4,000 patients worldwide have received treatment with Lumakras (known as Lumykras in Europe) through clinical development programs or commercial applications. (Bioon.com)