Tepmetko Associated With Frequent Side Effects for Some With NSCLC

Among patients with MET exon 14-altered non-small cell lung cancer (NSCLC), treatment with Tepmetko (tepotinib) was associated with a high frequency of side effects, although the safety profile is considered manageable, according to a pooled safety analysis of cohorts A and C of the phase 2 VISION trial.

Notably, these findings were consistent with prior reports from the trial. In the pooled safety analysis of cohorts A and C (313 patients), any-grade side effects occurred in 99% of patients, and grade 3 (severe) or higher side effects were reported in 68.4% of patients. Treatment-related side effects were observed in 91.7% of patients, including grade 3 or higher in 36.1% of patients. Any-grade serious side effects and serious treatment-related side effects occurred in 54.6% and 16% of patients, respectively. Side effects led to dose reductions in 33.2%, treatment interruptions in 43.8% and permanent discontinuation in 15.7% of patients. These rates of treatment-related side effects were 33.2%, 43.8% and 15.7%, respectively. Additionally, 13.7% of patients experienced a side effect that led to death, three of which were treatment related.

The most common treatment-related side effects included peripheral edema (any-grade, 67.7%; grade 3 or higher, 11.8%), hypoalbuminemia (25.2%; 3.8%), nausea (23.3%; 0.6%), diarrhea (22.7%; 0.3%), increased blood creatinine levels (22.0%; 1.3%), alanine aminotransferase (ALT) level elevation (14.1%; 2.2%), decreased appetite (11.5%; 0.3%), aspartate aminotransferase level elevation (11.2%; 1.9%) and amylase level increase (10.5%; 1.9%).

In total, 37.4% of patients required at least one dose reduction. The most common any-grade treatment-related side effect leading to dose reduction, treatment interruption and treatment discontinuation was peripheral edema (15.3%, 18.8%, and 6.1% of patients, respectively). Other treatment-related side effects leading to dose reductions were generalized edema (3.2%), edema (2.2%), pleural effusion (1.6%), increased blood creatinine levels (2.6%), hypoalbuminemia (1.3%), fatigue (1.0%), asthenia (1.0%) and localized edema (1.0%). Other treatment-related side effects leading to treatment interruptions included increased blood creatinine levels (5.8%), generalized edema (4.8%), edema (3.5%), pleural effusion (3.2%), increased ALT levels (2.6%), localized edema (2.2%) and nausea (2.2%). Other treatment-related side effects leading to treatment discontinuation included edema (1.3%), generalized edema (1.0%), pleural effusion (1.0%), interstitial lung disease (1.0%) and pneumonitis (1.0%).

Additionally, health-related quality of life (HRQOL) patient-reported outcome (PRO) scores remained stable with Tepmetko use. Investigators observed no meaningful change in European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) or EuroQol 5-Dimension 5-Level (EQ-5D-5L) scores up to 228 weeks. At the end of treatment, among patients evaluated for HRQOL, the mean change from baseline for the EORTC QLQ-C30 global health status (GHS) was –7.1 and the mean change for the EuroQol visual analogue scales (EQ-VAS) was –10; positive values signified improvement. The mean changes from baseline in the EORTC QLQ-lung cancer (LC13) symptom scores for cough, dyspnea and chest pain, respectively, were –6.1, 7.1 and –2.3; negative values signified improvement. Furthermore, the median time to deterioration of the EORTC QLQ-LC13 symptom scores for cough, chest pain, and dyspnea were 36.5 months, 30.4 months and 5.5 months, respectively.

“Throughout the VISION trial, patients completed questionnaires evaluating their QOL before and while receiving [Tepmetko],” Dr. Enriqueta Felip, lead study author and head of the Thoracic Cancer Unit at Hospital Universitari de la Vall d'Hebron in Barcelona, Spain, and coauthors explained in the conclusion of the poster presentation. “Overall, patients reported that health and QOL remained stable while receiving [Tepmetko]. Specific scores relating to symptoms experienced by patients with lung cancer were improved during treatment for symptoms such as cough and chest pain and remained stable for shortness of breath.”

What Was the Design of the VISION Trial of Tepmetko in Patients With MET-Altered NSCLC?

The VISION trial was a single-arm study evaluating Tepmetko in patients with advanced NSCLC harboring MET exon 14 skipping alterations.The study evaluated Tepmetko at a dose of 500 mg orally once daily and comprised three cohorts.

Eligible patients were at least 18 years of age, had histologically or cytologically confirmed NSCLC with MET exon 14 skipping alterations detected by liquid biopsy and/or tissue biopsy, measurable disease and an ECOG performance status of 0 or 1. Prior immunotherapy was permitted.

Patients were excluded if their tumors harbored EGFR mutations or ALK rearrangements, if they had received more than two prior lines of systemic therapy, or if they had prior exposure to MET or HGF inhibitors.

What Were the Baseline Patient Demographics in the VISION NSCLC Trial?

The median age of patients with MET exon 14 skipping NSCLC was 72 years. In total, 50.8% of patients were female, 73.8% of patients had an ECOG performance status of 1 and 47.6% of patients had received prior treatment.

At study entry, 47.6% of patients had received at least one prior systemic therapy. The median treatment duration was 7.5 months and 19 patients remained on Tepmetko for at least 48 months.

References

1. Felip E, Ferrara R, Veillon R, et al. Safety and patient-reported outcomes with tepotinib in patients with METex14 skipping NSCLC: ≥3 years follow-up of VISION. Presented at: 2025 IASLC World Conference on Lung Cancer; September 6-10, 2025; Barcelona, Spain. Poster P3.12.40.
2. Tepotinib phase II in NSCLC harboring MET alterations (VISION). ClinicalTrials.gov. Updated August 14, 2025. Accessed September 9, 2025. https://www.clinicaltrials.gov/study/NCT02864992

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