NEW YORK – Mirati Therapeutics on Monday said the US Food and Drug Administration has granted accelerated approval to Krazati (adagrasib) as a treatment for patients with locally advanced or metastatic non-small cell lung cancer who have received at least one systemic therapy and who have KRAS G12C-mutated tumors.
Simultaneously, the agency approved Agilent's Resolution ctDx FIRST liquid biopsy test and Qiagen's tissue-based therascreen KRAS RGQ PCR kit to identify patients with KRAS G12C mutations who may benefit from treatment with Krazati. "With tissue and blood modalities for companion diagnostics, patients have more flexibility, and clinicians have greater options for biomarker testing," Mirati said in a statement. "These solutions help to personalize a patient's treatment path."
Krazati is the second KRAS inhibitor to garner market approval for advanced, previously treated NSCLC in the US following the FDA approval of Amgen's KRAS inhibitor Lumakras (sotorasib) last year. At the time, the agency also approved Qiagen's Therascreen KRAS RGQ PCR kit and Guardant Health's liquid biopsy Guardant360 CDx to identify best responders.
The FDA approved Mirati's drug based on data from a Phase II cohort of the KRYSTAL-1 trial, which involved 116 patients with KRAS G12C-mutated advanced NSCLC who had previously gotten platinum-based treatment and an immune checkpoint inhibitor. The overall response rate was 43 percent and 80 percent achieved disease control. Median duration of response was 8.5 months.
A pooled analysis involving 132 patients from the above Phase II cohort and another Phase I/Ib NSCLC cohort from KRYSTAL-1 yielded similar response and disease control rates. Median duration of response was more than year, and median overall survival was 14.1 months, according to the pooled analysis.
Safety data on 366 patients in KRYSTAL-1 and KRYSTAL-12 showed adverse events such as nausea, diarrhea, vomiting, fatigue, and musculoskeletal pain are common; 13 percent of patients discontinued Krazati treatment due to the toxicities they experienced.
Having garnered accelerated approval from the FDA means that Mirati will have to demonstrate Krazati's safety and efficacy in confirmatory trials. Meanwhile, the San Diego-based drugmaker said it is launching a program called Mirati & Me, through which patients, caregivers, and the oncology community can get educational, financial, and emotional support services.