The Food and Drug Administration (FDA) has granted accelerated approval to Lumakras (sotorasib) 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 1 prior systemic therapy.
Sotorasib, an inhibitor of the RAS GTPase family, works by forming an irreversible, covalent bond with KRAS G12C that locks the protein in an inactive state and prevents downstream signaling without affecting wild-type KRAS. The approval was based on data from the single-arm, open-label, multicenter phase 1/2 CodeBreak 100 trial (ClinicalTrials.gov Identifier: NCT03600883), which evaluated the efficacy and safety of sotorasib in 124 patients with locally advanced or metastatic KRAS G12C-mutated NSCLC with disease progression after receiving an immune checkpoint inhibitor and/or platinum-based chemotherapy.
All patients received sotorasib 960mg orally once daily until disease progression or unacceptable toxicity. The main outcome measures were objective response rate (ORR) and duration of response (DOR), according to RECIST v1.1.
Findings demonstrated an ORR (the proportion of patients with at least a 30% decrease in tumor) of 36% (95% CI, 28-45), with 2% of patients achieving complete response and 35% having partial response. Additionally, 81% (95% CI, 73-87) of patients achieved disease control, defined as the proportion of patients who achieved complete response, partial response and stable disease for more than 3 months. The median DOR was 10 months; 58% of responders had a response duration of 6 months or more.
As for safety, the most common adverse reactions reported were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, cough, and laboratory abnormalities. Treatment with sotorasib can also cause interstitial lung disease/pneumonitis.
“Sotorasib represents a major advancement in oncology and changes the treatment paradigm for patients with KRAS G12C-mutated non-small cell lung cancer,” said Bob T. Li, MD, PhD, MPH, principal investigator at Memorial Sloan Kettering Cancer Center. “Patients with non-small cell lung cancer who have progressed beyond first-line treatment face a poor prognosis and have limited treatment options available to them. Sotorasib delivers a new option for these patients, and it is the first KRAS-targeted therapy to be approved after nearly 4 decades of research.”
Lumakras is supplied as 120mg tablets in cartons containing 2 bottles of 120 tablets or 1 bottle of 240 tablets.
Along with this approval, the FDA has also approved the QIAGEN therascreen KRAS RGQ PCR kit (QIAGEN GmbH) and the Guardant360 CDx (Guardant Health, Inc) as companion diagnostics for Lumakras. Patients should be selected for treatment with Lumakras based on the presence of KRAS G12C mutation in tumor or plasma specimens.
- FDA approves first targeted therapy for lung cancer mutation previously considered resistant to drug therapy. [press release]. Silver Spring, MD: US Food and Drug Administration; May 28, 2021.
- FDA approves Lumakras™ (sotorasib), the first and only targeted treatment for patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer. [press release]. Thousand Oaks, CA: Amgen; May 28, 2021.
- Lumakras [package insert]. Thousand Oaks, CA: Amgen; 2021.