On August 10, 2022, capmatinib was granted regular approval for patients with metastatic non–small cell lung cancer (NSCLC) with tumors having a mutation leading to mesenchymal-epithelial transition (MET) exon 14 skipping, as detected by a U.S. Food and Drug Administration–approved test.1 Capmatinib was granted accelerated approval in this indication in May 2020.
Supporting Efficacy Data
Conversion to regular approval was based on data from increased enrollment and longer follow-up in the multicenter GEOMETRY mono-1 trial (ClinicalTrials.gov identifier NCT02414139); initial findings in the trial supported accelerated approval. In the current analysis, 160 patients—including 100 previously treated and 60 treatment-naive patients—received capmatinib at 400 mg twice daily until disease progression or unacceptable toxicity.
Capmatinib has warnings/precautions for interstitial lung disease/pneumonitis, hepatotoxicity, pancreatic toxicity, risk of photosensitivity, and embryofetal toxicity.
Objective response on blinded independent review committee assessment was observed in 41 (68%, 95% confidence interval [CI] = 55%–80%) of 60 treatment-naive patients (5% complete response) and 44 (44%, 95% CI = 34%–54%) of 100 previously treated patients (all partial responses). Median durations of response were 16.6 months (95% CI = 8.4–22.1 months) and 9.7 months (95% CI = 5.6–13 months), respectively, with 49% and 36% of responses lasting ≥ 12 months.
How It Is Used
The recommended capmatinib dose is 400 mg orally twice daily. Product labeling provides instructions on dosage modification, including dose reduction, for adverse reactions including interstitial lung disease/pneumonitis, elevated liver enzymes, increased lipase or amylase, and pancreatitis. Concomitant use with strong and moderate CYP3A inducers (eg, clarithromycin, fluconazole) should be avoided.
Safety data are from 373 patients receiving capmatinib in the GEOMETRY mono-1 trial. The most common adverse events of any grade (≥ 20%) were edema, nausea, musculoskeletal pain, fatigue, vomiting, dyspnea, cough, and decreased appetite. The most common grade 3 or 4 laboratory abnormalities were decreased lymphocytes (14%), increased alanine aminotransferase (9%), and increased lipase (9%). Serious adverse events occurred in 53% of patients, most commonly dyspnea, pneumonia, pleural effusion, musculoskeletal pain, general physical health deterioration, interstitial lung disease/pneumonitis, and vomiting.
Capmatinib has warnings/precautions for interstitial lung disease/pneumonitis, hepatotoxicity, pancreatic toxicity, risk of photosensitivity, and embryofetal toxicity. Patients should be advised not to breastfeed while receiving capmatinib.
1. Tabrecta (capmatinib) tablets prescribing information, Novartis, August 2022. Available at www.accessdata.fda.gov/drugsatfda_docs/-label/2022/213591s004lbl.pdf. Accessed August 20, 2022.