Merck, a leading science and technology company, announced today important milestones for two combination studies of the investigational therapy tepotinib* in locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation and select MET dysregulations. These include progression-free survival (PFS) and overall survival (OS) data from the Phase Ib/II INSIGHT study of tepotinib plus the EGFR inhibitor gefitinib, and an update that the Phase II INSIGHT 2 study of tepotinib plus tyrosine kinase inhibitor (TKI) osimertinib is now open for enrollment. Tepotinib, discovered in-house at Merck, is an investigational oral MET inhibitor that underscores Merck's strategic focus on delivering innovative precision medicines to patients with cancer.

"The consistency of results across the clinical development program for tepotinib continues to highlight the potential for this investigational therapy in targeting select NSCLC mutations and alterations that are associated with aggressive tumor behavior and poor clinical prognosis," said Luciano Rossetti, Global Head of Research & Development for the Biopharma business of Merck. "We are committed to progressing tepotinib as part of our precision medicine strategy and our work to deliver new therapeutic options for people living with difficult-to-treat cancers, including NSCLC."

Additionally, Merck today announced it is now enrolling patients in the Phase II INSIGHT 2 study investigating tepotinib in combination with the TKI osimertinib in patients with EGFR-mutated, MET-amplified, locally advanced or metastatic NSCLC with acquired resistance to prior EGFR TKI therapy. The decision to initiate the INSIGHT 2 study is based on the encouraging findings seen in the Phase Ib/II INSIGHT study. Early data from this study presented at the 2019 American Association for Cancer Research Annual Meeting demonstrated clinical anti-tumor activity for the combination of tepotinib plus gefitinib compared with chemotherapy in patients with EGFR-mutant locally advanced or metastatic NSCLC with MET gene amplification who had disease progression after receiving an EGFR TKI, based on both investigator assessment and independent review committee assessment. Related grade ≥3 treatment-emergent adverse events (TEAEs) were reported in 6 (50.0%) patients treated with tepotinib plus gefitinib and 5 (71.4%) patients receiving chemotherapy. The most common related TEAEs in the tepotinib plus gefitinib arm were diarrhea (50.0%) and amylase increased (41.7%) and in the chemotherapy arm were anemia (57.1%), white blood cell count decreased (57.1%), neutrophil count decreased (57.1%) and nausea (42.9%). No new safety signals were observed.1 These data also indicate that MET amplification may be a biomarker predictive of response to tepotinib.

Tepotinib is also being investigated in the ongoing Phase II VISION study, evaluating tepotinib in advanced or metastatic NSCLC patients harboring MET alterations (MET exon 14 skipping alterations and MET amplifications) as monotherapy. Results from this study were presented in an oral presentation at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting.2 In March 2018, tepotinib's potential was recognized by the Japanese Ministry of Health, Labour and Welfare (MHLW), which granted SAKIGAKE 'fast-track' designation for tepotinib in advanced NSCLC harboring MET exon 14 skipping alterations.

About Non-Small Cell Lung Cancer 
With 2 million cases diagnosed annually, lung cancer (including trachea, bronchus and lung) is the most common type of cancer worldwide, and the leading cause of cancer-related death, with 1.7 million mortality cases worldwide.3Alterations of the MET signaling pathway, including MET exon 14 skipping alterations and MET amplifications, occur in 3-5% of NSCLC cases.4-6

About Tepotinib
Tepotinib, discovered in-house at Merck, is an investigational oral MET inhibitor that is designed to inhibit the oncogenic MET receptor signaling caused by MET (gene) alterations, including both MET exon 14 skipping alterations and MET amplifications, or MET protein overexpression. It has been designed to have a highly selective mechanism of action, with the potential to improve outcomes in aggressive tumors that have a poor prognosis and harbor these specific alterations.

Tepotinib is currently being investigated in NSCLC and Merck is actively assessing the potential of investigating tepotinib in combination with novel therapies and in other tumor indications.