The objective response rate was 46.5% among the 99 patients followed for 9 or more months, as assessed by independent reviewers. There were no complete responders, according to the reviewers.
However, the response rate according to investigator assessment was 55.6%, including two responses that were judged to be complete.
The median duration of response was 11.1 months according to reviewers and 14 months according to investigators.
“The success of this trial, alongside other studies on the same class of drugs, establishes MET exon 14 as an actionable target for non–small cell lung cancer,” said senior authorassistant professor in the department of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center, Houston.
Dr. Lefrom this trial as part of the American Society of Clinical Oncology virtual scientific program. Results were simultaneously in the New England Journal of Medicine.
The trial, dubbed VISION, already won tepotinibin Japan to treat NSCLC patients with MET exon 14–skipping mutations. The Food and Drug Administration has granted tepotinib breakthrough status, and Merck, the drug’s manufacturer, plans to submit tepotinib for review this year.
The VISION trial enrolled 152 patients with NSCLC – 99 with at least 9 months of follow-up and 53 with shorter follow-up. The patients’ MET exon 14 mutations were confirmed by liquid or tissue biopsy.
The patients’ median age at baseline was 74 years, 54% were men, and almost half had no smoking history. Patients received tepotinib at 500 mg daily until disease progression or intolerable toxicity.
Overall, the VISION results “compare favorably” with those from studies of other MET inhibitors, the investigators wrote.
The 46.5% objective response rate (per independent reviewers) included the 99 patients with follow-up of at least 9 months who were liquid- or tissue-biopsy positive (combined group). The response rate was 48.5% among the 66 patients with positive liquid biopsies and 50% among the 60 patients with positive tissue biopsies.
The median progression-free survival was 8.5 months in the combined group, 8.5 months in the liquid-biopsy group, and 11 months in the tissue-biopsy group. The median overall survival was 17.1 months, 15.8 months, and 22.3 months, respectively.
The 11 patients with brain metastases at baseline had results that were in line with the other patients’ results. Patients with brain metastases had an objective response rate of 54.5%, a median response duration of 9.5 months, and a median progression-free survival of 10.9 months.
Overall, 88.8% of patients reported adverse events related to treatment, including peripheral edema in 63.2%, nausea in 25.7%, and diarrhea in 21.7%.
Grade 3-4 adverse events occurred in 27% of patients. Peripheral edema was the most common of these events, reported in 7.2% of patients.
“Proactive monitoring for peripheral edema is recommended and can be managed with temporary discontinuation of tepotinib or dose reduction,” the investigators wrote.
The death of a 79-year-old patient with respiratory failure and dyspnea, secondary to interstitial lung disease, was the only death considered to be treatment related.
The study was funded by Merck. Dr. Le and other investigators disclosed relationships, including employment, with the company.
SOURCE: Le X et al. ASCO 2020, .