The New England Journal of Medicine

Tepotinib in Non–Small Cell Lung Cancer with MET Exon 14 Skipping Mutations

The VISION trial, which included a large MET exon 14 skipping cohort identified by Guardant360® liquid biopsy, found that tepotinib had durable antitumor activity in advanced NSCLC patients with MET exon 14 skipping mutations. The Overall Response Rate (ORR) was 46 to 50% for liquid versus tissue biopsy subgroups. The findings validate MET exon 14 skipping mutations as critical therapeutic targets and underscore the importance of routine testing for MET alterations.19

Sep 3, 2020


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Baseline cfDNA analysis provided valuable insight into the mutational profiles of patients with MET exon 14 skipping mutations.”

Key Findings19

  • Guardant360 detects guideline-complete alterations in advanced NSCLC patients including MET exon 14 skipping alterations
  • ORR and DCR equivalent in Guardant360 and tissue biopsy groups in the VISION trial MET exon 14 skipping NSCLC cohort

Clinical Summary

Complete genomic profiling with liquid biopsy reliably identifies patients with guideline-recommended targetable alterations including MET exon 14 skipping.

The VISION trial showed that the selective MET inhibitor, tepotinib, had durable clinical activity in patients with NSCLC with MET exon 14 skipping. Results are significant because outcomes with currently available therapies are typically poor in these patients, who are generally older (median age, 74 years).20-22 The relative paucity of data from elderly patients in these studies [using first-line immunotherapy with or without chemotherapy] warrants judicious use of these regimens in this population.23

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Key Findings25

  • 44% of eligible patients were unable to get complete genomic results from tissue biopsy
  • 2x as many patients had targetable alterations detected by Guardant360 and tissue testing (n=82) versus tissue testing alone (n=47)
  • 86% of patients had a response or stable disease based on RECIST criteria

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Key Findings26

  • The demands on tissue specimens from diagnostic stains and PD-L1 testing may leave little remaining for genomic profiling
  • Gaps in genomic biomarker testing can be overcome with new technologies

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Key Findings27

  • Comprehensive ctDNA testing can effectively guide therapy selection
  • Response rates to therapy selected based on Guardant360 results were consistent with those in tissue-based targeted therapy studies

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Key Findings

  • In the NSCLC cohort, 32.2% (19 patients) had a confirmed objective response (complete or partial response) and 88.1% (52 patients) had disease control (objective response or stable disease).
  • The median progression-free survival was 6.3 months.

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Key Findings24

  • Concordance between Guardant360 and tissue testing was greater than 90% for the four biomarkers with FDA-approved therapies
  • Guideline-recommended biomarker testing was completed for 95% of patients with Guardant360 vs. 31% with standard-of-care tissue testing
  • Turnaround time was ~1 week faster with Guardant360 vs. SOC tissue testing

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Key Findings19

  • Guardant360 detects guideline-complete alterations in advanced NSCLC patients, including MET exon 14 skipping alterations
  • ORR and DCR equivalent in Guardant360 and tissue biopsy groups in the VISION trial MET exon 14 skipping NSCLC cohort

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