The FDA has approved Guardant360, a liquid biopsy companion diagnostic for tumor mutation profiling or comprehensive genomic profiling to identify patients with locally advanced or metastatic non-small cell lung cancer who have a KRAS G12C mutation and may benefit from sotorasib.
The FDA has approved Guardant360, a liquid biopsy companion diagnostic (CDx) for tumor mutation profiling or comprehensive genomic profiling to identify patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who have a KRAS G12C mutation and may benefit from sotorasib (Lumakras), according to a press release by Guardant Health Inc.
Sotorasib is an FDA-approved KRAS G12C+ inhibitor meant to treat locally advanced or metastatic NSCLC who have received at least 1 prior line of systemic therapy. Clinical guidelines suggest comprehensive genomic profiling at diagnosis for all patients with advanced NSCLC in order to determine if the patient has an actionable mutation, which occurs in 13% of patients.
"The approval of Lumakras represents a significant medical advancement for patients with advanced non-small cell lung cancer who harbor the KRAS G12C mutation because it is the first and only targeted therapy now available to them," said Darryl Sleep, MD, Amgen chief medical officer and senior vice president of Medical Affairs, in a press release. "However, patients can only benefit from targeted therapies, or personalized treatments, if they are tested for biomarkers. Today’s FDA approval of Guardant360 CDx, offers an important development in biomarker testing by providing a high-quality, blood-based testing option for patients."
Approval for the diagnostic tool is based on the results of the CodeBreaK 100 phase 2 clinical trial (NCT03600883), which has an estimated enrollment of 733 patients. The study primary outcome of the study was the number of patients with treatment-emergent adverse events (TEAEs) up to 24 months, the number of subjects with grade 3 or higher TEAE up to 24 months, the number of patients with adverse events (AEs), the number of patients with clinically significant changes in vital signs, the number of patients with clinically significant changes in physical examination results, the number of patients with clinically significant changes in electrocardiograms, the number of patients with clinically significant changes in laboratory values, objective response rate (ORR), duration of response (DoR), disease control, progression-free survival (PFS), duration of stable disease, and time to response. Secondary outcomes included plasma concentration, are under the plasma concentration-time curve, overall survival (OS), and changes from baseline in physical function.
During the phase 2 portion of the study, patients received sotorasib at the recommended phase 2 dose. A second cohort was enrolled in a dose-comparison study to evaluate safety and efficacy.
In order to participate, patients must be 18 years old or older and have pathologically documented, locally advanced or metastatic KRAS G12C+ NSCLC identified through molecular testing. Patients with active brain metastases from non-brain tumors, myocardial infraction within 6 months of study day 1, or gastrointestinal tract disease that prevents the patient from taking oral medication are not eligible to participate.
The study found that patients who’s KRAS mutation was identified using Guardant360 did just as well as those identified using a traditional tissue-based biopsy. Guardant360 can deliver results from a blood draw within 7 days.
This ground-breaking new therapy from Amgen, Lumakras, underscores the importance of incorporating comprehensive genomic profiling in routine clinical practice to ensure all patients are evaluated for KRAS G12C and the growing list of other actionable mutations that can be treated with targeted therapies shown to significantly improve clinical outcomes," said Helmy Eltoukhy, chief executive officer of, in a press release. "By offering an FDA-approved companion diagnostic that can quickly deliver comprehensive results from a simple blood test, clinicians can have greater confidence using the test, and patients benefit from less invasive testing and shorter wait times to see whether they are eligible for a targeted therapy such as Lumakras."