FDA Grants Accelerated Approval To Sotorasib For KRAS G12C Mutated NSCLC

In May of 2021 the Food and Drug Administration granted an expedited approval for sotorasib(Lumakras(TM), Amgen, Inc.), one of the RAS GTPase inhibitors for patients of adult age with KRAS G12Cmutated locally advanced or metastatic non-small-cell lung cancer (NSCLC) as identified by an FDA approved test, and who have had at least one prior treatment.

The fda sotorasib has also approved the QIAGEN therascreen(r) KRAS the RGQ PCR kit (tissue) as well as the Guardant360(r) CDx (plasma) as diagnostic companions for Lumakras. If there is no mutation in a plasma sample, the tumor's tissues should be examined.

Approval was based upon CodeBreaK 100, a multicenter single-arm, open-label study (NCT03600883) that involved patients suffering from metastatic or locally advanced NSCLC that had KRAS G12C mutations. 

The most important efficacy outcome measures included objective responder rate (ORR) as per the RECIST 1.1 which was evaluated using a blinded central review independent of the study and duration of the response. In the study, ORR was 36 percent (95 percent CI: 28 percent, 45 percent) and a median period of about 10 months (range 1.3+ 11.1).

The most frequent adverse reactions (greater than 20 20%) included the following: diarrhea, musculoskeletal pain fatigue, nausea, and cough. 

Hepatotoxicity is the most common cause. The most frequent abnormalities in the laboratory (greater than 25 percent) were decreased lymphocytes diminished hemoglobin levels, an increase in aspartate aminotransferase levels, an increase in Alanine aminotransferase, and decreased calcium, increased alkaline-phosphatase as well as increased urine protein and reduced sodium.