Mirati Wins FDA Accelerated Approval For Lung Cancer Mutation

The USFDA has granted accelerated approval to Mirati Therapeutics’ Krazati (adagrasib), a targeted treatment for patients with advanced or metastatic non-small cell lung cancer (NSCLC) with a KRASG12C mutation. 

Krazati will be used as a second-line treatment for patients who have undergone a prior systemic therapy. The approval was based on a Phase 2 study called Krystal-1 where the drug met primary endpoints in overall response rate (ORR) and duration of response (DOR). 

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Overall Response Rate Of 43%

Krazati is optimized to sustain inhibition of the mutated KRASG12C protein, which regenerates every 24-48 hours. The drug penetrates the blood-brain barrier, which is important as brain metastases often occur in NSCLC and lead to poor prognosis. 

In Krystal-1, Krazati showed an ORR of 43%, and led to disease control in 80% of patients. The median DOR was 8.5 months. 

According to a pooled efficacy analysis of 132 patients from a Phase 1/1b NSCLC study and NSCLC cohorts from Krystal-1, Krazati showed an ORR of 44%, a disease control rate of 81%, and a median DOR of 12.5 months. The median overall survival was calculated at 14.1 months. In both trials, Krazati was given twice daily as a 600 mg oral capsule. 

On the safety side, a pooled analysis of 366 patients from Krystal-1 and a Phase 3 called Krystal-12 showed that the most common side effects of the drug were nausea, diarrhea, vomiting, and fatigue among others. Serious adverse events observed included gastrointestinal bleeding and colitis. 13% of patients had to discontinue due to an adverse reaction. 

Expanding Krazati’s Reach

Krazati received Breakthrough Therapy Designation in the US for its now approved indication in 2021. Further approvals of the drug depend on whether it shows clinical benefits in confirmatory trials. Outside the US, Mirati has filed for marketing approval for Krazati in the EU.  

The company has partnered with Agilent and Qiagen to develop blood- and tissue-based companion diagnostics for Krazati, giving clinicians and patients more options for biomarker testing. Mirati is launching Mirati & Me, a program aimed to facilitate drug coverage and financial, educational, and emotional support services. 

Author

Joy Lin

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