FDA Brief: Accelerated Approval Granted for Adagrasib in KRAS G12C–Mutated Lung Cancer

By: JNCCN 360 Staff
Posted: Thursday, December 15, 2022

On December 12, the U.S. Food and Drug Administration (FDA) granted accelerated approval to the RAS GTPase family inhibitor adagrasib (Krazati) for the treatment of adults with KRAS G12C–mutated locally advanced or metastatic non–small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy. The FDA also approved the QIAGEN therascreen KRAS RGQ PCR kit (tissue) and the Agilent Resolution ctDx FIRST Assay (plasma) as companion diagnostics for adagrasib. If no mutation is detected in a plasma specimen, the tumor tissue should be tested.

Approval was based on KRYSTAL-1, a multicenter, single-arm, open-label clinical trial (ClinicalTrials.gov identifier NCT03785249), which included patients with locally advanced or metastatic NSCLC with KRAS G12C mutations. Efficacy was evaluated in 112 patients whose disease had progressed on or after platinum-based chemotherapy and an immune checkpoint inhibitor, given either concurrently or sequentially. Patients received adagrasib at 600 mg orally twice daily until disease progression or unacceptable toxicity.

The main efficacy outcome measures were confirmed objective response rate, according to Response Evaluation Criteria in Solid Tumors version 1.1, as evaluated by blinded independent central review, and duration of response. The objective response rate was 43% (95% confidence interval [CI] = 34%–53%), and the median duration of response was 8.5 months (95% CI = 6.2–13.8 months).

The most common adverse reactions (≥ 20%) were diarrhea, nausea, fatigue, vomiting, musculoskeletal pain, hepatotoxicity, renal impairment, dyspnea, edema, decreased appetite, cough, pneumonia, dizziness, constipation, abdominal pain, and QTc interval prolongation. The most common laboratory abnormalities (≥ 25%) were 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.

The recommended adagrasib tablet dose is 600 mg orally twice daily until disease progression or unacceptable toxicity. For full prescribing information, visit adagrasib.

U.S. Food and Drug Administration

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