The open-label, phase 2 VISION study evaluated the efficacy and safety of tepotinib, a highly selective oral MET inhibitor, in patients with advanced NSCLC with MET alterations.
MET exon 14 skipping mutations occur in approximately 3% to 4% of NSCLC cases and correlate with aggressive tumor behavior and poor clinical prognosis.1 Researchers reported the results of the open-label, phase 2 VISION study in patients with MET exon 14 skipping mutations.
The VISION study included 152 patients with advanced or metastatic disease who received tepotinib 500 mg once daily.1 The efficacy population consisted of 99 of the 152 patients with a follow-up of at least 9 months. The primary end point was the objective response by independent review in the efficacy population. Response rates were also analyzed according to whether the presence of MET exon 14 skipping mutation was detected by a liquid biopsy (N = 66) or tissue biopsy (N = 60). Secondary end points were investigator-assessed objective response, duration of response, progression-free survival (PFS), and overall survival (OS).
At a median follow-up of 17.4 months, the objective response rate by independent review was 46% (95% CI, 36-57; all partial responses) and was similar regardless of baseline characteristics and number of lines of previous therapy.1 The median duration of response was 11.1 months (95% CI, 7.2 months–not estimable) in the combined biopsy group, 9.9 months (95% CI, 7.2 months-not estimable) in the liquid biopsy group, and 15.7 months (95% CI, 9.7 months-not estimable) in the tissue biopsy group. The objective response rate was 48% (95% CI, 36-61) and 50% (95% CI, 37-63) in the liquid biopsy group and tissue biopsy group, respectively. The investigator-assessed objective response rate was 56% (95% CI, 45-66) and was similar regardless of the previous therapy received for advanced or metastatic disease.
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.1 Median PFS by independent review was 8.5 months (95% CI, 6.7-11.0 months) in the efficacy population, 8.5 months (95% CI, 5.1=11.0 months) in the liquid biopsy group, and 11.0 months (95% CI, 5.1-17.1 months) in the tissue biopsy group. OS data were not mature (median duration of OS, 17.1 months; 95% CI, 12.0–26.8 months).
Overall, grade 3 or higher treatment-related adverse events were reported in 28% of the patients at a median follow-up of 11.8 months.1 Peripheral edema (7%,) was the most common treatment-related adverse event of grade 3 or higher. Serious treatment-related adverse events were reported in 15% of patients. Treatment-related adverse events led to permanent discontinuation of tepotinib in 11% of patients and dose reduction in 33% of patients. One death, which was due to respiratory failure and dyspnea secondary to interstitial lung disease, was considered related to treatment.
- Paik PK, Felip E, Veillon R, et al. Tepotinib in non-small-cell lung cancer with MET exon 14 skipping mutations. N Engl J Med. 2020;383:931-943.