The FDA approved the kinase inhibitor capmatinib (Tabrecta, Novartis) for the treatment of adults with metastatic non-small cell lung cancer (NSCLC) with mutations that lead to mesenchymal–epithelial transition exon 14 skipping (METex14).

The FDA also approved the FoundationOne CDx assay as a companion diagnostic to aid in the detection of mutations that lead to METex14 in tumor tissue.

“Non-small cell lung cancer is a complex disease, with many different possible mutations that may encourage the cancer’s growth,” said Juergen Wolf, MD, from University Hospital Cologne’s Centre for Integrated Oncology, in Germany, and lead investigator of the GEOMETRY study, which supported capmatinib’s approval. “MET exon 14 skipping is a known oncogenic driver,” Dr. Wolf noted. “With today’s decision by the FDA, we can now test for and treat this challenging form of lung cancer with a targeted therapy, offering new hope for patients with NSCLC harboring this type of mutation.”

Mutations leading to METex14 are found in 3% to 4% of patients with lung cancer.

During the mono-1 phase 2, multicenter, nonrandomized, open-label, multicohort GEOMETRY trial, Dr. Wolf and his co-investigators evaluated 97 adults with metastatic NSCLC who had mutations that lead to METex14. Patients received 400 mg of the kinase inhibitor capmatinib orally twice daily until disease progression or unacceptable toxicity. The major efficacy outcome measure was overall response rate (ORR) by blinded independent review committee assessment per RECIST (Response Evaluation Criteria In Solid Tumors) v1.1. An additional efficacy outcome measure was duration of response (DOR). The efficacy population included 28 patients who had never undergone treatment for NSCLC and 69 previously treated patients. 

The ORR for the 28 patients who had not received previous treatment was 68% (95% CI, 48%-84%), with 4% having a complete response and 64% having a partial response. The ORR for the 69 previously treated patients was 41% (95% CI, 29%-53%), with all having a partial response. In capmatinib-treated patients the median DOR was 12.6 months (95% CI, 5.5-25.3 months) in treatment-naive patients (19 responders) and 9.7 months (95% CI, 5.5-13.0 months) in previously treated patients (28 responders). DOR lasted 12 months or longer in 47% treatment-naive patients and 32% of those who had been treated.

The most common treatment-related adverse events (AEs)—occurring in at least 20% of patients—were peripheral edema, nausea, fatigue, vomiting, dyspnea and decreased appetite. 

Capmatinib also can cause serious AEs, including interstitial lung disease and pneumonitis. Capmatinib should be permanently discontinued in patients with these AEs. 

In addition, capmatinib can cause hepatotoxicity, and health care professionals should monitor a patient’s liver function before they start capmatinib and while they are on treatment. If a patient experiences hepatotoxicity, the dose of capmatinib should be reduced or the drug should be temporarily or permanently discontinued. 

Based on a clear positive signal for phototoxicity in laboratory studies in cells, patients taking capmatinib may be more sensitive to sunlight and should be advised to cover their skin and use sunscreen and not to tan while taking capmatinib.

Capmatinib can cause harm to a developing fetus or newborn baby. Health care professionals should advise pregnant women of this risk and should advise women of reproductive potential, and males with female partners of reproductive potential, to use contraception during treatment with capmatinib and for one week after the last dose.

For more information, view the full prescribing information for capmatinib. 

—Clinical Oncology News Staff

Based on press releases from the FDA and Novartis.