Today, Merck KGaA announced that the U.S. FDA has granted Breakthrough Therapy Designation to its MET inhibitor tepotinib for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping mutations whose disease has progressed following platinum-based chemotherapy. Prior to this, tepotinib had already received Fast Track designation in Japan.

Lung cancer is the most common cancer and one of the leading causes of cancer-related deaths worldwide. Each year, 2 million people are diagnosed with lung cancer, and 1.7 million die from it. Among patients with non-small cell lung cancer (NSCLC), approximately 3%–5% exhibit MET gene amplification or exon 14 mutations. Currently, there are no approved targeted therapies for MET mutations, and the prognosis for these patients remains poor.

Tepotinib is a highly selective oral MET inhibitor developed by Merck KGaA, demonstrating antitumor activity in patients with non-small cell lung cancer (NSCLC) characterized by MET overexpression or amplification. In addition to its application in clinical trials for the treatment of patients with NSCLC, tepotinib is also being evaluated in Phase 2 clinical trials for the treatment of patients with hepatocellular carcinoma.

▲Molecular structure of tepotinib (Image source: PubChem)

This breakthrough therapy designation is based on the ongoing Phase 2 clinical study named VISION. A total of 73 patients with metastatic non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping mutations, confirmed by either tissue biopsy (TBx) or liquid biopsy (LBx), were enrolled in the trial. The trial data indicate that tepotinib may improve treatment options for these patients. For patients confirmed by LBx, the overall response rate (ORR) assessed by the Independent Review Committee (IRC) was 50%, while the investigator-assessed ORR was 55.3%. For patients confirmed by TBx, the corresponding figures were 45.1% and 54.9%, respectively. In terms of median duration of response (DOR), the IRC-assessed values for patients confirmed by LBx and TBx were 12.4 months and 15.7 months, respectively. The investigator-assessed DOR for these two patient groups was 17.1 months and 14.3 months, respectively.

“Tepotinib has demonstrated highly encouraging overall response rates and durable efficacy in patients with metastatic non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping mutations, as confirmed by tissue biopsy (TBx) or liquid biopsy (LBx),” said Dr. Luciano Rossetti, Head of Global Biopharma R&D at Merck KGaA. “This breakthrough therapy designation further underscores the therapeutic potential of tepotinib. We look forward to making this medication available to eligible NSCLC patients who may benefit from it as soon as possible.”

References:

[1] Merck KGaA, Darmstadt, Germany, Announces FDA Breakthrough Therapy Designation for Investigational Therapy Tepotinib in Patients with Metastatic NSCLC with METex14 Skipping Alterations, Retrieved September 11, 2019, from https://www.prnewswire.com/news-releases/merck-kgaa-darmstadt-germany-announces-fda-breakthrough-therapy-designation-for-investigational-therapy-tepotinib-in-patients-with-metastatic-nsclc-with-metex14-skipping-alterations-300915825.html

[2] Merck KGaA official website, Retrieved from https://www.emdgroup.com/en/research/biopharma-pipeline.html

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