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Tepotinib Treatment in Patients With MET Exon 14-Skipping Non-Small Cell Lung Cancer: Long-term Follow-up of the
Julien Mazieres1, Paul K Paik2,3, Marina C Garassino4,5
1CHU de Toulouse, Université Paul Sabatier, Toulouse, France.
Importance:
MET inhibitors have recently demonstrated clinical activity in patients with MET exon 14 (METex14)-skipping non-small cell lung cancer (NSCLC); however, data with longer follow-up and in larger populations are needed to further optimize therapeutic approaches.
Objective:
To assess the long-term efficacy and safety of tepotinib, a potent and highly selective MET inhibitor, in patients with METex14-skipping NSCLC in the VISION study.
Design, Setting, And Participants:
The VISION phase 2 nonrandomized clinical trial was a multicohort, open-label, multicenter study that enrolled patients with METex14-skipping advanced/metastatic NSCLC (cohorts A and C) from September 2016 to May 2021. Cohort C (>18 months' follow-up) was an independent cohort, designed to confirm findings from cohort A (>35 months' follow-up). Data cutoff was November 20, 2022.
Intervention:
Patients received tepotinib, 500 mg (450 mg active moiety), once daily.
Main Outcomes And Measures:
The primary end point was objective response by independent review committee (RECIST v1.1). Secondary end points included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.
Results:
Cohorts A and C included 313 patients (50.8% female, 33.9% Asian; median [range] age, 72 [41-94] years). The objective response rate (ORR) was 51.4% (95% CI, 45.8%-57.1%) with a median (m)DOR of 18.0 (95% CI, 12.4-46.4) months. In cohort C (n = 161), an ORR of 55.9% (95% CI, 47.9%-63.7%) with an mDOR of 20.8 (95% CI, 12.6-not estimable [NE]) months was reported across treatment lines, comparable to cohort A (n = 152). In treatment-naive patients (cohorts A and C; n = 164), ORR was 57.3% (95% CI, 49.4%-65.0%) and mDOR was 46.4 (95% CI, 13.8-NE) months. In previously treated patients (n = 149), ORR was 45.0% (95% CI, 36.8%-53.3%) and mDOR was 12.6 (95% CI, 9.5-18.5) months. Peripheral edema, the most common treatment-related adverse event, occurred in 210 patients (67.1%) (35 [11.2%] experienced grade ≥3 events).
Conclusions And Relevance:
The findings from cohort C in this nonrandomized clinical trial supported the results from original cohort A. Overall, the long-term outcomes of VISION demonstrated robust and durable clinical activity following treatment with tepotinib, particularly in the treatment-naive setting, in the largest known clinical trial of patients with METex14-skipping NSCLC, supporting the global approvals of tepotinib and enabling clinicians to implement this therapeutic approach for such patients.
Trial Registration:
ClinicalTrials.gov Identifier: NCT02864992.
Insights
Tepotinib demonstrated significant long-term efficacy and safety in patients with MET exon 14-skipping non-small cell lung cancer (NSCLC). This study supports tepotinib as a valuable treatment option for this patient population.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- MET inhibitors show clinical activity in MET exon 14 (METex14)-skipping non-small cell lung cancer (NSCLC).
- Longer follow-up and larger population data are needed to optimize therapeutic strategies for METex14-skipping NSCLC.
Purpose of the Study:
- To evaluate the long-term efficacy and safety of tepotinib, a MET inhibitor, in patients with METex14-skipping NSCLC within the VISION study.
- To confirm findings from earlier cohorts with extended follow-up.
Main Methods:
- Phase 2, nonrandomized, open-label, multicenter clinical trial (VISION study).
- Enrolled patients with METex14-skipping advanced/metastatic NSCLC (Cohorts A and C).
- Patients received tepotinib 500 mg once daily; data cutoff November 20, 2022.
Main Results:
- Overall response rate (ORR) was 51.4% (95% CI, 45.8%-57.1%) with a median duration of response (mDOR) of 18.0 months.
- Cohort C (n=161) showed an ORR of 55.9% and mDOR of 20.8 months, comparable to Cohort A.
- Treatment-naive patients had higher ORR (57.3%) and longer mDOR (46.4 months) compared to previously treated patients.
Conclusions:
- Long-term outcomes from the VISION study confirm robust and durable clinical activity of tepotinib in METex14-skipping NSCLC.
- Tepotinib demonstrates particular efficacy in treatment-naive patients.
- These findings support global approvals and clinical implementation of tepotinib for this indication.
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