Tepotinib Continues to Show Positive Outcomes in METex14-Skipping NSCLC


In the VISION trial, tepotinib led to clinically meaningful results in treatment-naïve and pretreated patients with METex14-skipping non–small cell lung cancer, supporting the use of MET inhibitors for this patient population.

human anatomy and smoky lungs© vitanovski - stock.adobe.com

human anatomy and smoky lungs© vitanovski - stock.adobe.com

Long-term data from the phase 2 VISION trial (NCT02864992) showed robust and durable clinical activity after treatment with tepotinib (Tepmetko) in patients with locally advanced or metastatic MET exon 14 (METex14)-skipping non–small cell lung cancer (NSCLC), particularly in the treatment-naïve setting.1

Findings from cohort C of the nonrandomized trial, which included 161 patients, showed that at a median follow-up of 18 months, the objective response rate (ORR) was 55.9% and median duration of response (mDOR) was 20.8 months across treatment lines. These data support previous results from cohort A (n = 152) of the trial.

Across both cohorts A and C, ORR was 57.3% (95% CI, 49.4%-65.0%) with an mDOR of 46.4 months (95% CI, 13.8-not evaluable) in the 164 treatment-naive patients evaluated. Among patients who were previously treated (n = 149), the ORR observed was 45.0% (95% CI, 36.8%-53.3%) and mDOR was 12.6 (95% CI, 9.5-18.5) months.

"These data are particularly meaningful for patients with MET exon 14-skipping-positive NSCLC, who tend to be older and who are not, as a result, well-represented in the pivotal phase 3 studies that have cemented chemotherapy and immunotherapy as standards of care. Indeed, overall survival for our older patients can be as short as 8-10 months, as reported in recent prospective studies, and so a median OS of 20 months is encouraging to see, particularly as it’s maintained on longer follow-up," Paul K. Paik, MD, clinical director, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, told Targeted OncologyTM.

The nonrandomized, multicohort, open-label, multicenter VISION study sought to assess the safety and efficacy of the potent and highly selective MET inhibitor tepotinib for the treatment of patients with METex14-skipping NSCLC. Cohort C of the study was an independent cohort which was designed to confirm the findings from cohort A of the study.

Patients were eligible for inclusion in the study if they were 18 years of age or older with measurable disease, an ECOG performance status of 0 or 1, histologically or cytologically confirmed advanced NSCLC, and were treatment naïve in the first line or pretreated patients with no more than 2 lines of prior therapy.2 Patients were required to have MET alterations, especially METex14-skipping alterations.

In cohorts A and C, 313 patients were included and baseline characteristics were broadly consistent between cohorts.1 A total of 50.8% of patients were female, 33.9% were Asian, and the median age among those enrolled was 72 years (range, 41-94). A total of 47.6% of patients had a smoking history, 73.8% had an ECOG performance status of 1, and 80.5% had adenocarcinoma.

The data cutoff was November 20, 2022. In the study, patients received tepotinib at a dose of 500 mg (450 mg active moiety) once a day. The primary end point assessed was ORR by independent review committee, and secondary end points included DOR, progression-free survival (PFS), overall survival (OS), and safety.

Additional study findings showed that with a median follow-up of 32.6 (range, 0.3-71.9) months across both cohorts, the ORR was 51.4% (95% CI, 45.8%-57.1%) with a mDOR of 18.0 (95% CI, 12.4-46.4) months. The median PFS was 11.2 (95% CI, 9.5-13.8) months, and the median OS was 19.6 (95% CI, 16.2-22.9) months.

For safety, treatment-related AEs (TRAEs) occurred in 287 (91.7%) patients in cohorts A and C. Grade 3 or higher TRAEs were observed in 109 (34.8%) patients. A total of 105 patients (33.5%) doses reduced and 46 (14.7%) discontinued treatment due to TRAEs.

The most common TRAE seen in 67.1% of patients was peripheral edema. Thirty-five (11.2%) patients had grade 3 or higher peripheral edema. Other TRAEs seen in over 20% of patients were hypoalbuminemia (23.6%), nausea (23.3%), diarrhea (22.4%), and blood creatinine level increase (22.0%). These TRAEs were mostly grades 1 to 2.

Overall, this study is the largest known clinical trial of patients with METex14-skipping NSCLC. Data supports the global approvals of tepotinib and the use of this agent for the treatment of this patient population.

"The next steps are and should be focused on a few different fronts. First, we need to better understand resistance mechanisms in order to improve the efficacy of existing approaches and extend the number of lines of therapies available to our patients with MET exon 14-skipping-positive NSCLC. Second, we need to better understand the unique side effect profile associated with MET inhibitors, particularly peripheral edema, so that we can further improve the quality of life of our patients while on treatment. Third, we need to explore other ways of targeting MET to expand upon the arsenal of drugs available for our patients," added Paik.

  1. Mazieres J, Paik PK, Garassino MC, et al. Tepotinib treatment in patients with MET exon 14-skipping non-small cell lung cancer: long-term follow-up of the VISION phase 2 nonrandomized clinical trial [published correction appears in JAMA Oncol. 2023 Jul 20;:]. JAMA Oncol. 2023;9(9):1260-1266. doi:10.1001/jamaoncol.2023.1962
  2. Tepotinib phase II in NSCLC harboring MET alterations (VISION). ClinicalTrials.gov. Updated June 9, 2023. Accessed October 19, 2023. https://tinyurl.com/bdd7ydsb
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