On February 15, 2024, tepotinib (Tepmetko)-—a kinase inhibitor directed against MET, including variants with exon 14 skipping—was granted regular approval for patients with metastatic non–small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition (MET) exon 14–skipping alterations.1
Tepotinib was previously granted accelerated approval for this indication in February 2021 based on initial overall response rate and duration of response in the VISION trial (ClinicalTrials.gov identifier NCT02864992). The conversion to regular approval was based on findings in an additional 161 patients (n = 313) and an added 28 months of follow-up to assess duration of response in the trial.
Supporting Efficacy Data
Patients received tepotinib at 450 mg once daily until disease progression or unacceptable toxicity. On blinded independent review committee assessment, an objective response was observed in 57% (95% confidence interval [CI] = 49%–65%) of 164 treatment-naive patients, with 40% of responders having a response at 12 months or more. Among 149 previously treated patents, an objective response was observed in 45% (95% CI = 37%–53%), with 36% of responders having a response at 12 months or more.
How It Is Used
The recommended tepotinib dose is 450 mg orally once daily until disease progression or unacceptable toxicity. Product labeling provides instructions on dosage modification, including dose reduction, for adverse reactions including interstitial lung disease/pneumonitis, increased alanine and aspartate aminotransferase, increased lipase or amylase, and pancreatitis.
Safety Profile
Among the 313 patients in VISION, the most common adverse events of any grade were edema (81%), nausea (31%), fatigue (30%), musculoskeletal pain (30%), diarrhea (29%), dyspnea (24%), decreased appetite (21%), and rash (21%). The most common grade 3 or 4 adverse events included edema (16%), pleural effusion (4.2%), pneumonia (3.8%), and musculoskeletal pain (3.2%). The most common grade 3 or 4 laboratory abnormalities were decreased lymphocytes (15%), decreased albumin (9%), decreased sodium (9%), and increased gamma-glutamyltransferase (6%).
OF NOTE
Tepotinib has warnings/precautions for interstitial lung disease/pneumonitis, hepatotoxicity, pancreatic toxicity, and embryofetal toxicity.
KEY POINTS
- Tepotinib was granted regular approval for patients with NSCLC harboring MET exon 14–skipping alterations.
- The recommended tepotinib dose is 450 mg orally once daily until disease progression or unacceptable toxicity.
Serious adverse events occurred in 51% of patients, most commonly pleural effusion (6%), pneumonia (6%), edema (5%), general health deterioration (3.8%), dyspnea (3.5%), musculoskeletal pain (2.9%), and pulmonary embolism (2.2%). Adverse events led to discontinuation of treatment in 25% of patients, most commonly edema (8%), pleural effusion (1.6%), and general health deterioration (1.6%). Adverse events led to death in 1.9% of patients, including pneumonitis (0.3%), hepatic failure (0.3%), dyspnea from fluid overload (0.3%), pneumonia (0.3%), sepsis (0.3%), and death of unknown cause (0.3%).
Tepotinib has warnings/precautions for interstitial lung disease/pneumonitis, hepatotoxicity, pancreatic toxicity, and embryofetal toxicity. Patients should be advised not to breastfeed while receiving tepotinib.
REFERENCE
1. Tepmetko (tepotinib) tablets, for oral use, prescribing information, EMD Serono, Inc, February 2024. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/214096s003lbl.pdf. Accessed March 28, 2024.
