FDA Grants Priority Review to Tepotinib for the Treatment of NSCLC with METex14 Skipping Mutations


The new drug application was based on results from the pivotal ongoing, single-arm, phase 2 VISION study evaluating tepotinib monotherapy in patients with advanced NSCLC with METex14 skipping alterations.

The FDA has accepted and granted priority review to the new drug application (NDA) for once-daily, orally-dosed tepotinib for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to mesenchymal-epithelial transition exon 14 (METex14) skipping, as detected by an FDA-approved test, according to Merck KGaA, the developer of the agent.1

The NDA was based on results from the pivotal ongoing, single-arm, phase 2 VISION study, which is evaluating tepotinib as monotherapy in patients with advanced NSCLC with METex14 skipping alterations prospectively assessed by liquid and/or tissue biopsy.

METex14 skipping alterations drive a particularly aggressive form of NSCLC in a patient population that is generally elderly, facing poor clinical prognosis and in urgent need of new therapeutic options,” Luciano Rossetti, global head of Research & Development for the Biopharma business of Merck KGaA in Darmstadt, Germany, said in a press release. “With this acceptance and review under the [Real-Time Oncology Review] program, we look forward to working with FDA and to making this precision medicine available to patients in the US as soon as possible.”

Data from the primary analysis of the VISION study were published in The New England Journal of Medicine and presented during the 2020 American Society of Clinical Oncology Virtual Scientific Program.2

Patients enrolled in the study are administered 500 mg of tepotinib once daily.2 The primary end point is objective response by independent review among patients who had previously undergone at least 9 months of follow-up. In addition, response is being analyzed according to whether the presence of a MET exon 14 skipping mutation was detected on liquid biopsy or tissue biopsy.

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% CI, 36-57), with a median duration of response of 11.1 months (95% CI, 7.2 to could not be estimated) in the combined-biopsy group. Moreover, the response rate was 48% (95% CI, 36-61) among 66 patients in the liquid-biopsy group and 50% (95% CI, 37-63) 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, 45-66) and was found to be similar regardless of the previous therapy received for advanced or metastatic disease.

Grade 3 or higher adverse events (AEs) deemed to be related to tepotinib therapy were observed in 28% of the study cohort, including peripheral edema in 7%. Notably, AEs led to permanent discontinuation of tepotinib in 11% of patients. Further, 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.

In September 2019, tepotinib was granted breakthrough therapy designation by the FDA for the treatment of patients with metastatic NSCLC harboring METex14 skipping alterations who progressed following platinum-based cancer therapy. Tepotinib also became the first oral MET inhibitor indicated for the treatment of advanced NSCLC harboring MET gene alterations to receive a regulatory approval globally in March 2020, with the Japanese Ministry of Health, Labour and Welfare (MHLW) granting approval for the treatment of patients with unresectable, advanced, or recurrent NSCLC with METex14 skipping alterations.


1. FDA Accepts Filing of New Drug Application for Tepotinib for the Treatment of Patients with Metastatic NSCLC with METex14 Skipping Alterations [news release]. Darmstadt, Germany. Published August 25, 2020. Accessed August 25, 2020. https://www.emdgroup.com/en/news/tepotinib-file-acceptance-fda.html

2. Paik PK, Felip E, Veillon R, et al. Tepotinib in Non-Small-Cell Lung Cancer with MET Exon 14 Skipping Mutations. The New England Journal of Medicine. doi: 10.1056/NEJMoa2004407.

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