August 2021: The FDA granted accelerated approval to sotorasib (LumakrasTM, Amgen, Inc.), a RAS GTPase family inhibitor, for adult patients with KRAS G12C mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) who have received at least one prior systemic therapy, as determined by an FDA-approved test.
As companion diagnostics for Lumakras, the FDA has approved the QIAGEN therascreen® KRAS RGQ PCR kit (tissue) and the Guardant360® CDx (plasma). The tumour tissue should be evaluated if no mutation is found in the plasma sample.
The approval was based on CodeBreaK 100, a multicenter, single-arm, open label clinical study (NCT03600883) that included patients with KRAS G12C mutations who had locally progressed or metastatic NSCLC. The efficacy of the drug was tested in 124 patients whose disease had progressed on or after at least one previous systemic therapy. Sotorasib 960 mg orally once a day was given to patients until disease progression or intolerable toxicity.
The primary effectiveness outcomes were the objective response rate (ORR) according to RECIST 1.1, as determined by a blinded independent central review, and response length. With a median response time of 10 months (range 1.3+, 11.1), the ORR was 36 percent (95 percent CI: 28 percent, 45 percent).
Diarrhea, musculoskeletal pain, nausea, exhaustion, hepatotoxicity, and cough were the most prevalent side effects (20%). Decreased lymphocytes, decreased haemoglobin, increased aspartate aminotransferase, increased alanine aminotransferase, decreased calcium, increased alkaline phosphatase, increased urine protein, and decreased sodium were the most prevalent laboratory abnormalities (25 percent).
Sotorasib is taken once a day, with or without food, at a dose of 960 mg.
The 960 mg dose was approved based on available clinical evidence as well as pharmacokinetic and pharmacodynamic simulations that supported the amount. The FDA is demanding a postmarketing trial as part of the evaluation for this accelerated approval to see if a lower dose will have a similar therapeutic effect.
Referință: https://www.fda.gov/
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