Amgen has announced that it investigational unique cancer drug AMG 510 that targets tumours caused by mutations in the KRAS gene has progressed into the second phase of clinical trials.
According to Amgen, AMG 510 is the first unique cancer drug to reach clinical trials that inhibits a mutant KRAS protein. The firm noted that this feature was only possible because of promising safety and efficacy results in preliminary human studies and excellent results in animal studies.
— Amgen Oncology (@AmgenOncology) December 21, 2019
The particular mutant inhibited by AMG 510 (KRASG12C), is present in approximately 13percent of lung adenocarcinomas, 3percent of colorectal cancers, and 2percent of other solid tumours.
David M. Reese, MD, executive vice president of Research and Development at Amgen, expressed his joy at the development of the unique cancer drug.
We are pleased to share how our team of scientists at Amgen were the first to exploit the previously hidden groove on the protein surface to finally identify a potential drug against this essential oncogenic protein.
How unique cancer drug works?
According to reports, the unique cancer drug, AMG 510 can induce tumour-cell killing as both a monotherapy and also with other therapies, has an impact on the immune system that may render tumour cells particularly sensitive to immunotherapy.
KRAS, identified over 30 years ago as a proto-oncogene, is one of the most frequently mutated oncogenes in human cancer.
Amgen researchers first identified the novel histidine 95 (H95) groove located on an inactive KRASG12C protein.
Through extensive compound screening and structure-based design, AMG 510 emerged as the top investigational candidate from the optimisation of a series of H95 groove-binding molecules.
It is designed to irreversibly bind to KRASG12C protein and permanently lock it in an inactive state, leading to inhibition of tumour cell growth in KRASG12C driven tumours.
In preclinical experiments, AMG 510 demonstrated favourable potency and selectivity, and induced regression in mice bearing KRASG12C mutated tumours.
FDA grants fast track to AMG 510
The US Food and Drug Administration (FDA) has earlier granted a fast track designation to the unique cancer drug AMG 510, for the treatment of patients with previously treated metastatic non-small cell lung cancer (NSCLC) harbouring a KRASG12C mutation.
Additional data from the ongoing Phase 1 clinical trial evaluating AMG 510 was recently presented at the 2019 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer and at the European Society for Medical Oncology 2019 Congress.
The findings covered 34 patients with NSCLC treated with AMG 510, including 19 who were treated in the dose-escalation phase with doses starting at 180 mg and 15 who were treated in the expansion phase at the determined phase II dose of 960 mg once daily.
No dose-limiting toxicities were observed among the patients with NSCLC, and although four patients discontinued treatment, none were due to adverse events. Twenty-seven patients remained on medication at the time of data cutoff.
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