FDA Accepts Filing of New Drug Application for Tepotinib for the Treatment of Patients with Metastatic NSCLC with METex14 Skipping Alterations

Merck KGaA, Darmstadt, Germany, today announced that the US Food and Drug Administration (FDA) has accepted and granted Priority Review to the new drug application (NDA) for once-daily, orally-dosed tepotinib*

25 Aug 2020 | Darmstadt, Germany
  • Tepotinib granted Priority Review and is being evaluated under FDA Real-Time Oncology Review (RTOR) pilot program
  • Tepotinib is a highly targeted inhibitor of c-MET that is administered as a once-daily oral tablet
  • Data show robust, consistent and durable clinical response across different lines of therapy, including in patients with brain metastases, and as assessed by liquid biopsy or tissue biopsy

Merck KGaA, Darmstadt, Germany, a leading science and technology company, today announced that the US Food and Drug Administration (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. Tepotinib was granted Priority Review and is being reviewed by the FDA under its Real-Time Oncology Review (RTOR) pilot program, which is intended to create a more efficient review process to bring safe and effective treatments to patients as early as possible.1 Priority Review is intended to accelerate evaluation of applications for drugs that could offer improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications.2 Tepotinib was granted Breakthrough Therapy Designation by the FDA in September 2019 for the treatment of patients with metastatic NSCLC harboring METex14 skipping alterations who progressed following platinum-based cancer therapy.

The application is based on results from the pivotal ongoing, single-arm Phase II VISION study (NCT02864992) evaluating tepotinib as monotherapy in patients with advanced NSCLC with MET exon 14 (METex14) skipping alterations prospectively assessed by liquid and/or tissue biopsy. Results demonstrate consistent response rate and durable anti-tumor activity across lines of treatment including in patients with brain metastases and in patients assessed by both liquid biopsy (LBx) and tissue biopsy (TBx). Data from the primary analysis of the VISION study were published in The New England Journal of Medicine (NEJM) on May 29, 2020 and presented during the American Society of Clinical Oncology (ASCO) ASCO20 Virtual Scientific Program.3

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,” said Luciano Rossetti, Global Head of Research & Development for the Biopharma business of Merck KGaA, Darmstadt, Germany. “With this acceptance and review under the RTOR program, we look forward to working with FDA and to making this precision medicine available to patients in the U.S. as soon as possible.”

In the US in 2020, there were approximately 228,000 new cases of lung cancer and more than 135,000 deaths from lung cancer.4 Alterations of the MET signaling pathway are found in various cancer types, including 3% to 5% of NSCLC cases, and correlate with aggressive tumor behavior and poor clinical prognosis.5-7 Patients with NSCLC harboring METex14 skipping tend to be older than those with NSCLC harboring other alterations.8 In the Phase II VISION study, the patient population is generally characterized as elderly, with a median age of 74.0 years, and as having poor clinical prognosis typical of NSCLC with METex14 skipping alterations.

In March 2020, tepotinib became the first oral MET inhibitor indicated for the treatment of advanced NSCLC harboring MET gene alterations to receive a regulatory approval globally, with the Japanese Ministry of Health, Labour and Welfare (MHLW) approval for the treatment of patients with unresectable, advanced or recurrent NSCLC with METex14 skipping alterations.

*Tepotinib is currently under clinical investigation and not yet approved in any markets outside of Japan.



  1. US Food and Drug Administration. Real-Time Oncology Review Pilot Program. https://www.fda.gov/about-fda/oncology-center-excellence/real-time-oncology-review-pilot-program. Accessed August 2020.
  2. US Food and Drug Administration. Priority Review.  https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review. Accessed August 2020.
  3. Paik PK et al. Tepotinib in non–small-cell lung cancer with MET exon 14 skipping mutations. N Engl J Med 2020 May 29; [e-pub]. (https://doi.org/10.1056/NEJMoa2004407)
  4. American Cancer Society. Key Statistics for Lung Cancer. American Cancer Society. Atlanta, Ga. 2020. Accessed at https://www.cancer.org/cancer/lung-cancer/about/key-statistics.html. 1 July 2020.
  5. Reungwetwattana T, et al. Lung Cancer 2017;103:27-37.
  6. Mo HN, et al. Chronic Dis Transl Med 2017;3(3):148-153.
  7. Lutterbach B, et al. Cancer Res 2007;67:2081-8.
  8. Schrock AB et al. J Thorac Oncol 2016;11(9):1493-1502.
  9. Global Burden of Disease Cancer Collaboration. JAMA Oncol. 2019;5:1749–1768
  10. Bladt F, et al. Clin Cancer Res 2013;19:2941-2951.


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