FDA Approves First Targeted Non-Small Cell Lung Cancer Therapy

FDA recently approved Amgen’s Lumakras, the first treatment for adult patients with non-small cell lung cancer whose tumors have a specific type of genetic mutation and who have received at least one prior systemic therapy.

Lumakras was approved specifically for tumors with KRAS G12C, a type of mutation in a group of genes that help regulate cell growth and division, an FDA spokesperson said. This is the first approved targeted therapy for tumors with any type of KRAS mutation. 

KRAS accounts for nearly 25 percent of mutations in non-small cell lung cancers and KRAS G12C mutations represent about 13 percent of mutations in non-small cell lung cancers.  

“KRAS mutations have long been considered resistant to drug therapy, representing a true unmet need for patients with certain types of cancer,” 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, said in the announcement.

“Today’s approval represents a significant step towards a future where more patients will have a personalized treatment approach,” Pazdur continued. 

FDA approved a 960-milligram dose of Lumakras based on available clinical data, as well as pharmacokinetic and pharmacodynamic modeling that support the approved dose.

Specifically, the agency based its approval off 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 or platinum-based chemotherapy.

Researchers looked at objective response rate, which was the proportion of patients whose tumor was destroyed or reduced, as well as duration of response.

The objective response rate was 36 percent, and 58 percent of those patients had duration response of six months or longer. 

The most common side effects of Lumakras include musculoskeletal pain, nausea, fatigue, and cough. FDA highlighted that Lumakras should be withheld if patients develop symptoms of interstitial lung disease and permanently discontinued if clinicians confirm interstitial lung disease. 

Additionally, 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.

Lumakras was approved using FDA’s accelerated approval pathway. 

The accelerated approval pathway allows the agency to approve drugs for serious conditions where there is unmet medical need and a drug is shown to have effects that are likely to provide clinical benefit to patients.

Lumakras also received orphan drug designation, which helps encourage the development of drugs for rare diseases.

"The FDA approval of LUMAKRAS is a breakthrough moment for patients with KRAS G12C-mutated non-small cell lung cancer because there is now a targeted therapy for this common, but previously elusive, mutation," David M. Reese, MD, executive vice president of research and development at Amgen, said in an announcement following the approval.  

"The LUMAKRAS development program was a race against cancer for Amgen's scientists and clinical trial investigators who together have now successfully delivered this new medicine to patients in less than three years—from first patient dosed to U.S. regulatory approval,” Reese continued. 

Non-small cell lung cancer accounts for nearly 84 percent of the 2.2 million new lung cancer diagnoses each year worldwide, including about 236,000 new cases in the US.

According to Amgen, KRAS G12C is one of the most prevalent driver mutations in non-small cell lung cancer, with 13 percent of patients with non-squamous non-small cell lung cancer in the US having KRAS G12C mutation. 

In May 2021, FDA approved Roche’s first-line treatment, Tecentriq, for adult patients with metastatic non-small cell lung cancer, as well as Janssen’s Rybrevant as the first targeted therapy for patients with subset of non-small cell lung cancer.