Tepotinib Achieves 46% Response Rate in MET Exon 14 Skipping NSCLC with Liquid and Tissue Biopsy Concordance
The VISION phase 2 trial demonstrated that tepotinib achieved a 46% response rate in MET exon 14 skipping-mutant NSCLC, with similar efficacy whether the mutation was detected by liquid biopsy (48%) or tissue biopsy (50%). Molecular response measured in circulating free DNA was observed in 67% of patients with matched samples, validating liquid biopsy as both a diagnostic and monitoring tool for this actionable driver alteration.
The original study
Tepotinib in Non-Small-Cell Lung Cancer with
- Authors
- Paik PK, Felip E, Veillon R, Sakai H, Cortot AB, Garassino MC, et al.
- Journal
- The New England journal of medicine
- Type
- Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't
- PMID
- 32469185
Original abstract
BACKGROUND: A splice-site mutation that results in a loss of transcription of exon 14 in the oncogenic driver MET occurs in 3 to 4% of patients with non-small-cell lung cancer (NSCLC). We evaluated the efficacy and safety of tepotinib, a highly selective MET inhibitor, in this patient population. METHODS: In this open-label, phase 2 study, we administered tepotinib (at a dose of 500 mg) once daily in patients with advanced or metastatic NSCLC with a confirmed MET exon 14 skipping mutation. The primary end point was the objective response by independent review among patients who had undergone at least 9 months of follow-up. The response was also analyzed according to whether the presence of a MET exon 14 skipping mutation was detected on liquid biopsy or tissue biopsy. RESULTS: As of January 1, 2020, a total of 152 patients had received tepotinib, and 99 patients had been followed for at least 9 months. The response rate by independent review was 46% (95% confidence interval [CI], 36 to 57), with a median duration of response of 11.1 months (95% CI, 7.2 to could not be estimated) in the combined-biopsy group. The response rate was 48% (95% CI, 36 to 61) among 66 patients in the liquid-biopsy group and 50% (95% CI, 37 to 63) among 60 patients in the tissue-biopsy group; 27 patients had positive results according to both methods. The investigator-assessed response rate was 56% (95% CI, 45 to 66) and was similar regardless of the previous therapy received for advanced or metastatic disease. Adverse events of grade 3 or higher that were considered by investigators to be related to tepotinib therapy were reported in 28% of the patients, including peripheral edema in 7%. Adverse events led to permanent discontinuation of tepotinib in 11% of the patients. A molecular response, as measured in circulating free DNA, was observed in 67% of the patients with matched liquid-biopsy samples at baseline and during treatment. CONCLUSIONS: Among patients with advanced NSCLC with a confirmed MET exon 14 skipping mutation, the use of tepotinib was associated with a partial response in approximately half the patients. Peripheral edema was the main toxic effect of grade 3 or higher. (Funded by Merck [Darmstadt, Germany]; VISION ClinicalTrials.gov number, NCT02864992.).