FDA Approves Tepotinib for METex14-Altered Metastatic NSCLC

Feb 3, 2021

February 3, 2021- The FDA has granted an accelerated approval to tepotinib for adult patients with metastatic non–small cell lung cancer harboring MET exon 14 skipping alterations.

The FDA has granted an accelerated approval to tepotinib (Tepmetko) for the treatment of adult patients with metastatic non–small cell lung cancer harboring MET exon 14 skipping alterations.1

The regulatory decision was based on data from in the phase 2 VISION trial (NCT02864992), which showed that the MET inhibitor induced an objective response rate (ORR) of 43% (95% CI, 32%-56%) among 69 treatment-naïve patients per blinded independent review committee (IRC) using RECIST v1.1 criteria.2

Moreover, the median duration of response (DOR) with the agent was 10.8 months (95% CI, 6.9–estimable). Among the 83 previously treated patients included in the trial, the ORR was also 43% (95% CI, 33%-55%); in this subgroup, with a median DOR was 11.1 months (95% CI, 9.5-18.5).

In the multicenter, non-randomized, open-label, multicohort, phase 2 trial, patients with METex14 skipping mutations were enrolled to cohort A, those with MET amplification were assigned to cohort B, and those with METex14 skipping mutations are currently being recruited to cohort C for a confirmatory analysis of the findings from cohort A.3

To be eligible for enrollment to cohort A, patients had to have locally advanced or metastatic disease that harbored a METex14 skipping mutation; this must have been confirmed with a liquid or tissue biopsy. Patients could not have received more than 2 previous lines of treatment. Notably, those with brain metastases were allowed to participate as long as they were not symptomatic.

In the trial, participants were administered oral tepotinib at a dose of 500 mg, once daily, given in 21-day cycles. Treatment continued until either intolerable toxicity or disease progression.

The primary end point of the trial was ORR per IRC; this was examined across 3 patient cohorts: liquid biopsy– and/or tissue biopsy–assessed tumors (n = 33), liquid biopsy–assessed tumors (n = 66), and tissue biopsy–assessed tumors (n = 60). Secondary objectives of the trial comprised investigator-assessed ORR, DOR, progression-free survival (PFS), and safety.

As of January 2020, 152 patients had received tepotinib, 99 of whom were determined to be efficacy evaluable. At the time of data cutoff, 60 of 152 patients in the safety population and 22 of the 99 in the efficacy population continued to receive study treatment.

Patients on the trial had a median age of 74 years, the majority (75%) were white, and more than half (54%) were male. Seventy-seven percent of patients had an ECOG performance status of 1. Moreover, half of the participants had a smoking history, and 43%, 34%, and 23% of patients received 0, 1, or at least 2 previous lines of treatment, respectively, for advanced or metastatic disease.

Earlier data presented during the 2020 ASCO Virtual Scientific Meeting demonstrated that responses to tepotinib were comparable between the liquid- and tissue-biopsy cohorts. In the liquid-biopsy cohort, the ORR per IRC was 48.5% versus 50.0% in the tissue-biopsy cohort. In the combined biopsy cohort, the ORR with tepotinib was highest, at 55.6%. Here, the median DOR was 14.0 months and the disease control rate (DCR) was 72.7%.

Per investigator assessment, the ORRs in the liquid- and tissue-biopsy cohorts were 56.1% and 61.7%, respectively. In the liquid-biopsy cohort, the median DOR by IRC was 9.9 months versus 14.0 months by investigator assessment; the DCRs were 65.2% and 69.7%, respectively. In the tissue-biopsy cohort, the median DOR by IRC was 15.7 months versus 16.4 months by investigator assessment; the DCRs were 68.3% and 78.3%, respectively.

Tumor shrinkage was reported in 89% of patients who received treatment with tepotinib.

In the combined biopsy cohort, the median PFS with tepotinib was 8.5 months (95% CI, 6.7-11.0) per IRC; it was 8.6 months (95% CI, 6.7-11.2) per investigator assessment. The median PFS in those who were just given a liquid biopsy was 8.5 months versus 11.0 months in those who just received tissue biopsy.

The median OS in the combined biopsy cohort was 17.1 months (95% CI, 12.0-26.8). In the liquid-biopsy cohort, the median OS was 15.8 months, while it was 22.3 months in the tissue-biopsy cohort.

In 11 patients who had brain metastases at baseline, outcomes with tepotinib proved to be comparable to that of the overall study population. In these patients, the ORR per IRC was 54.5% (95% CI, 23.4%-83.3%), the median DOR was 9.5 months (95% CI, 6.6-NE), and the median PFS was 10.9 months (95% CI, 8.0-NE).

Regarding safety, the most frequently reported adverse effects with tepotinib included edema, fatigue, nausea, diarrhea, musculoskeletal pain, and dyspnea. The FDA notes that the agent can also lead to interstitial lung disease, hepatotoxicity, and embryo-fetal toxicity.


  1. FDA grants accelerated approval to tepotinib for metastatic non-small cell lung cancer. News release. FDA. February 3, 2021. Accessed February 3, 2021. http://bit.ly/3az71Cj.
  2. Le X, Felip E, Veillon R, et al. Primary efficacy and biomarker analyses from the VISON study of tepotinib in patients (pts) with non-small cell lung cancer (NSCLC) with METex14 skipping. J Clin Oncol. 2020;38(suppl 15):9556. doi:10.1200/JCO.2020.38.15_suppl.9556
  3. Paik PK, Felip E, Veillon R, et al. Tepotinib in non—small cell lung cancer with MET exon 14 skipping mutations. N Eng J Med. Published online May 29, 2020. doi:10.1056/NEJMoa2004407
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