Krazati Approved for KRAS^G12C-Mutated Locally Advanced or Metastatic NSCLC

The Food and Drug Administration (FDA) has granted accelerated approval to Krazati (adagrasib) for the treatment of adults with KRAS^G12C-mutation locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA approved test, who have received at least 1 prior systemic therapy.

Krazati is a highly selective and potent oral small molecule inhibitor of KRAS^G12C. The accelerated approval was based on data from the open-label registration-enabling cohort of the phase 2 KRYSTAL-1 study (ClinicalTrials.gov Identifier: NCT03785249), which evaluated adagrasib in 112 adults with NSCLC harboring the KRAS^G12C mutation following prior systemic therapy. Patients received adagrasib 600mg orally twice a day until disease progression or unacceptable toxicity.

After a median follow-up of 9 months, results showed an objective response rate of 43% (95% CI, 34-53) and a disease control rate of 80% (95% CI, 71-87) in the intent-to-treat population, based on central independent review. The median duration of response (DOR) was 8.5 months (95% CI, 6.2-13.8) with 58% of patients having a DOR lasting at least 6 months. 

The most common adverse reactions reported with adagrasib were diarrhea, nausea, fatigue, vomiting, musculoskeletal pain, hepatotoxicity, renal impairment, dyspnea, edema, decreased appetite, cough, pneumonia, dizziness, constipation, abdominal pain, and QTc interval prolongation. Laboratory abnormalities included decreased lymphocytes, increased aspartate aminotransferase, decreased sodium, decreased hemoglobin, increased creatinine, decreased albumin, increased alanine aminotransferase, increased lipase, decreased platelets, decreased magnesium, and decreased potassium.

Krazati is supplied as 200mg tablets in 120- and 180-count bottles. The product is expected to be available immediately.

The FDA has also approved the Qiagen therascreen KRAS RGQ PCR kit (tissue) and the Agilent Resolution ctDx FIRST Assay (plasma) as companion diagnostics for Krazati. The tumor tissue should be tested if no mutation is detected in a plasma specimen.

References

1. FDA grants accelerated approval to adagrasib for KRAS G12C-mutated NSCLC. News release. US Food and Drug Administration. December 12, 2022. Accessed December 13, 2022. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-adagrasib-kras-g12c-mutated-nsclc.
2. Mirati Therapeutics announces US FDA accelerated approval of Krazati™ (adagrasib) as a targeted treatment option for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a KRAS^G12C mutation. News release. Mirati Therapeutics. December 12, 2022. Accessed December 13, 2022. https://www.multivu.com/players/English/8999051-mirati-therapeutics-fda-accelerated-approval-of-krazati-adagrasib/.
3. Krazati. Package insert. Mirati Therapeutics, Inc.; 2022. Accessed December 13, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/216340s000lbl.pdf.

This article originally appeared on MPR