The US Food and Drug Administration (FDA) has granted accelerated approval for Mirati Therapeutics’ Krazati (adagrasib) for treatment of mutated locally advanced or metastatic non-small cell lung cancer in adults. This accelerated approval has been based on data received from Phase II registration enabling cohort of the KRYSTAL-1 clinical trial of 600mg oral dose taken twice a day. This Mirati drug has got approval as a second line treatment for non-small cell lung cancer characterized by a subset of KRAS mutations called KRAS G12C. Krazati is designed to bind to mutant form of KRAS G12C protein and stop it from sending the in controlled signs that are responsible for driving cancer. The FDA decision is based on the results of an open-label Phase 2 study that tested the drug in 116 patients. These patients have previously been treated with chemotherapy and a type of immunotherapy called checkpoint inhibitor.
Krazati is the second to hit the market that blocks a specific mutation in a protein, KRAS. Another KRAS inhibitor, Lumakras, is already available to treat patients with advanced lung cancer as a second-line therapy. Though researchers knew the protein had ties to cancer but couldn’t figure out how to get an antibody a toehold on it. In the time period of two years, FDA has granted accelerated approval to two KRAS blockers.
In this study, the main aim was to assess the number and size of tumors as well as the duration of response. The results showed 43% of objective response rate and median duration of response of 12.5 months. The common adverse reactions reported in the Krazati study were nausea, fatigue, vomiting, liver toxicity etc. One key differentiating feature of the Mirati drug is its ability to penetrative into the brain. This indication is approved under accelerated approval based on overall response rate and duration of response.
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