Amgen (AMGN) announced new data from its ongoing Phase I clinical trial evaluating AMG 510 in patients with previously treated KRAS G12C-mutated solid tumors. AMG 510 is a first-in-class investigational oral therapy designed to selectively and irreversibly target the KRAS (G12C) protein. The additional follow-up in a larger group of patients with non-small cell lung cancer (NSCLC) continued to show anti-tumor activity with no dose-limiting toxicities.
TrialSite News follows up with brief Question and Answer summary that is part of TrialWatch.
What is AMG 510?
AMG 510 attaches to the mutant KRAS protein and prevents it from signaling to other cells, thereby slowing or stopping cancer growth. It is taken orally (e.g. by mouth). AMG is the first KRASG12C to reach the clinical stage. Thus far it has evidenced anti-tumor activity when administered as a monotherapy in patients with locally-advanced or metastatic KRAS. G12C AMG510 seeks to crack the KRAS code by exploiting a previously hidden groove on the protein surface. AMG 510 is designed to lock KRAS protein into an inactive state. Amgen believes that AMG 510 represents big potential as both a monotherapy and in combination with other targeted immune therapies.
What is KRAS?
KRAS has been a target of active exploration in cancer research as it was identified as one of the first oncogenes over 30 years ago. The subject of more than three decades of research, the RAS gene family are the most frequently mutated oncogenes in human cancers. Within this family, KRAS is the most prevalent variant and is particularly common in solid tumors. A specific mutation known as KRAS G12C accounts for approximately 13% of non-small cell lung cancers, 3-5% of colorectal cancers and one to two percent of numerous other solid tumors. Approximately 30,000 patients are diagnosed each year in the United States with KRAS G12C-driven cancers.KRASG12C has been considered “undruggable” due to a lack of traditional small molecule binding pockets on the protein. Amgen is exploring the potential of KRASG12C inhibition across a broad variety of tumor types.
What is this Phase I Study?
The Phase I first in human, open-label, multicenter study enrolled patients with KRAS G12C mutant solid tumors. Eligible patients were heavily pretreated with at least two or more prior lines of treatment, consistent with their tumor type and stage of the disease. The primary endpoint is safety, and key secondary endpoints include pharmacokinetics, objective response rate (assessed every six weeks), duration of response and progression-free survival. Patients were enrolled in four dose cohorts: 180 mg, 360 mg, 720 mg, and 960 mg, taken orally once a day.
What are the Results Thus Far?
Initial data from the Phase I study were presented at the 55th Annual Meeting of the American Society of Clinical Oncology (ASCO) earlier this year. The additional follow-up in a larger group of patients being presented at WCLC includes a subset of 34 NSCLC patients enrolled, with 23 of the patients being evaluable for efficacy. 13 of the evaluable patients received the target dose of 960 mg once daily, of which seven (54%) achieved a partial response at one or more time points and six (46%) achieved stable disease, for a disease control rate of 100%.
Of the 34 NSCLC patients enrolled, there have been no observed dose-limiting toxicities and no adverse events leading to discontinuation. 27 of these patients remain on treatment. Of the 34 patients, only 9 (26.5%) reported treatment-related adverse events (TRAEs) of grade 1 or 2. Three patients reported grade 3 TRAEs (anemia and diarrhea). There were no grade 4 or higher TRAEs.
Lead Investigator Comment: Washington University School of Medicine
Ramaswamy Govindan, MD, Principal Investigator, and Professor Washington University School of Medicine St. Louis reports “There is a need for targeted treatments for specific driver mutations of cancer that do not have an approved therapy.” Dr. Govindan continued “These data continue to show encouraging anti-tumor activity with AMG, underscoring the potential to close the treatment gap for non-small cell lung cancer patients with previously treated KRAS G12C-mutated NSCLC.”
Call to Action: Are you monitoring KRAS G12C mutated NSCLC (lung cancer)? It would be wise to monitor the progress of this study.