To support the commercialization of the blood-based companion diagnostic test Guardant360 companion diagnostic for AMG 510, Guardant Health, Inc, will collaborate with Amgen, developer of AMG 510, and pursue an FDA Pre-Market Approval as a companion diagnostic for AMG 510 in patients with metastatic non–small cell lung cancer with a KRAS G12C mutation, according to a press release.
To support the commercialization of the blood-based companion diagnostic (CDx) test Guardant360 CDx for AMG 510, Guardant Health, Inc, will collaborate with Amgen, developer of AMG 510, and pursue an FDA Pre-Market Approval as a CDx for AMG 510 in patients with metastatic nonsmall cell lung cancer (NSCLC) with aKRASG12C mutation, according to a press release.1
In addition to the FDA Pre-Market Approval Guardant360 CDx, Guardant Health plans to pursue regulatory clearance through the Japan Pharmaceutical and Medical Device Agency and European Medicines Agency as a companion diagnostic for the agent.
Patients are currently being enrolled in a phase II clinical trial of the KRAS G12C inhibitor. Investigational AMG 510 is a first-in-class drug that selectively and irreversibly targets the KRAS G12C protein.KRASG12C mutations are present in about 13% of all patients with NSCLC, and the treatment options for these particular patients remain limited.
“The potential of AMG 510 to specifically targetKRASG12C, a mutation that was once thought to be undruggable, represents a major therapeutic advancement in advanced NSCLC,” Sanket Agrawal, general manager of the KRAS program at Amgen, said. “Amgen is committed to driving broad accessibility to biomarker testing. Collaborating with Guardant Health to develop their Guardant360 blood test as a companion diagnostic will help ensure that all eligible NSCLC patients receive biomarker testing.”
In September 2019,AMG 510 was granted a Fast Track Designation from the FDAfor the treatment of patients with the KRASG12C-mutation with metastatic NSCLC. The designation was based on updated data from the phase I trial, which was presented at the IASLC World Conference on Lung Cancer (WCLC).2
Nineteen patients were treated in the dose-escalation phase starting doses at 180 mg of AMG 510, and 15 patients were treated in the expansion phase which used the determined recommended phase II dose of 960 mg once daily. The agent induced a promising disease control rate of 96% in these patients with NSCLC who harbor theKRASG12C mutation.
The objective response rate (ORR) was 48% in the 23 evaluable patients who had completed the first 6-week CT scan or had early progressive disease. Eleven patients had achieved partial responses (PRs), and 11 reached stable disease (SD).
Out of the 13 patients who received the phase II dose, 7 achieved a PR (54%), and 6 patients had SD (46%). The ORR in this patient cohort was 54% with a disease control rate of 100%.
The data suggest a favorable safety profile, and there were no dose-limiting toxicities observed with AMG 510. No patients discontinued treatment due to adverse events (AEs). However, 4 patients discontinued treatment on study.
Grade 1/2 treatment-related AEs (TRAEs) were observed in 26.5% of patients, while 8.8% of patients experienced grade 3 events of anemia and diarrhea. No TRAEs of grade 4 or greater were reported in these data.
“In a recent head-to-head study of liquid versus tissue testing, Guardant demonstrated that patients with advanced NSCLC are not consistently receiving adequate genotyping results from tissue,” AmirAli Talasaz, PhD, president at Guardant Health, said. “We believe that the development of Guardant360 CDx will lead to consistently delivered guideline-complete genotyping results along with other important genomic information to patients and their providers through blood, which will ultimately increase the number of patients who are identified as eligible for targeted therapies, including AMG 510, and thus improve access to these potentially life-changing treatments.”