FDA Approves Tabrecta, the First Targeted Drug for Patients with Non-Small Cell Lung Cancer and MET exon 14

The Food and Drug Administration (FDA) has approved the targeted drug Tabrecta (capmatinib) to treat adults with metastatic non-small cell lung cancer (NSCLC) that has the MET exon 14 skipping gene mutation.

Tabrecta is the first therapy approved by the FDA specifically to treat NSCLC with mutations that lead to epithelial-mesenchymal transition (EMT), which is MET exon 14 skipping.

Tabrecta is approved for patients who are new to treatment and also those who have received previous therapies, regardless of prior treatment type.

Along with the drug approval, the FDA gave the green light to a companion diagnostic, the FoundationOne CDx assay, which can identify these mutations in patients.

In epithelial—mesenchymal transition (EMT), the cells that line an organ lose their polarity and ability to adhere to other cells, giving them the ability to invade tissues and organs. MET exon 14 skipping means that a segment of RNA that should prompt the production of a specific protein stops sending those messages.

The spread of cancer consists of a sequential series of events and MET exon 14 skipping is recognized as a critical event in this process, the FDA stated in a press release about the approval. Mutations leading to MET exon 14 skipping are found in 3% to 4% of patients with lung cancer, the agency stated.

“Lung cancer is increasingly being divided into multiple subsets of molecularly defined populations with drugs being developed to target these specific groups,” said Dr. Richard Pazdur, 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, in the release.

Taken orally, Tabrecta works by blocking a key protein that drives metastatic NSCLC in these patients. The FDA approved it based on the results of a clinical trial involving patients with NSCLC who had mutations leading to MET exon 14 skipping; their tumors did not express the proteins EGFR or ALK.

The evaluated study population included 28 patients who had never undergone treatment for NSCLC and 69 previously treated patients. The overall response rate (ORR; the percentage of participants who experienced a prespecified amount of tumor shrinkage) for the 28 participants was 68%, with 4% having a complete response and 64% having a partial response.

The ORR for the 69 participants was 41%, with all having a partial response. Of the responding participants who had never undergone treatment for NSCLC, 47% had a duration of response lasting 12 months or longer compared with 32.1% of the responding participants who had been previously treated.

Common side effects for patients taking Tabrecta included swelling of the legs, nausea, fatigue, vomiting, shortness of breath and decreased appetite.

Tabrecta may cause serious side effects including scarring or inflammation of the lungs. It may also cause damage to liver cells or harm a developing fetus or newborn baby. Patients may be more sensitive to sunlight when they take Tabrecta and should take precautions to cover their skin and use sunscreen.

Tabrecta was approved under the FDA’s accelerated approval, breakthrough designation and priority review programs, which provide for a quicker review of drugs that treat serious or life-threatening diseases and represent a meaningful advantage over existing treatments.

Continued approval for this indication may be contingent upon verification of these results in confirmatory clinical trials.

Check back for what you need to know regarding this approval.