The US FDA approved sotorasib (Lumakras, Amgen Inc) as the first treatment for adult patients with non-small cell lung cancer whose tumors have a specific type of genetic mutation called KRAS G12C and who have received at least one prior systemic therapy, according to an agency news announcement.
The FDA said sotorasib is the first approved targeted therapy for tumors with any KRAS mutation, which accounts for approximately 25% of mutations in non-small cell lung cancers. KRAS is a type of mutation in a group of genes that help regulate cell growth and division. KRAS G12C mutations represent about 13% of mutations in non-small cell lung cancers.
Researchers evaluated the efficacy of Lumakras in a study of 124 patients with locally advanced or metastatic KRAS G12C-mutated non-small cell lung cancer with disease progression after receiving an immune checkpoint inhibitor and/or platinum-based chemotherapy. The major outcomes measured were objective response rate (proportion of patients whose tumor is destroyed or reduced) and duration of response. The objective response rate was 36% and 58% of those patients had a duration of response of six months or longer.
The approved 960 milligram dose is based on available clinical data, as well as pharmacokinetic and pharmacodynamic modeling that support the approved dose. As part of the evaluation for this accelerated approval, the agency is requiring a postmarketing trial to investigate whether a lower dose will have a similar clinical effect.
“KRAS mutations have long been considered resistant to drug therapy, representing a true unmet need for patients with certain types of cancer,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “Today’s approval represents a significant step towards a future where more patients will have a personalized treatment approach.”
The most common side effects of Lumakras include diarrhea, musculoskeletal pain, nausea, fatigue, liver damage and cough. Lumakras should be withheld if patients develop symptoms of interstitial lung disease and permanently discontinued if interstitial lung disease is confirmed. Health care professionals should monitor a patient’s liver function tests prior to starting and when taking Lumakras. If a patient develops liver damage, Lumakras should be withheld, dose reduced or permanently discontinued. Patients should avoid taking acid-reducing agents, drugs that induce or are substrates for certain enzymes in the liver and drugs that are substrates of the P-glycoprotein while taking Lumakras.
Related Approvals
Along with Lumakras, the FDA also approved the Qiagen therascreen KRAS RGQ PCR kit and the Guardant360 CDx as companion diagnostics for Lumakras. The Qiagen GmbH test analyzes tumor tissue and the Guardant Health Inc test analyzes plasma specimens to determine if Lumakras is an appropriate treatment for patients. If no mutation is detected in a plasma specimen, the patient’s tumor should be tested, the FDA says.
