Updated Results for Investigational Therapy Tepotinib Presented at WCLC 2019

Results include progression-free survival and overall survival data from Phase Ib/II INSIGHT study

Phase II INSIGHT 2studynow open for enrollment forpatients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation and select MET dysregulations

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DARMSTADT,Germany,Sept. 9,2019 -- 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,andan update thatthe 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 resultsacross the clinical development program fortepotinib 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."

Data were presented on September 8 at the 2019 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer (#WCLC19),including 18-month follow-up data from the Phase Ib/II INSIGHT study evaluating tepotinib in combination with the EGFR inhibitor gefitinib compared with standard chemotherapy in patients with EGFR-mutant locally advanced or metastatic NSCLC with MET protein overexpression or MET gene amplification who had disease progression after receiving an EGFR TKI. These results include updated PFS data as well as the first OS data for patients in both the MET overexpression and MET amplification cohorts of this study. These data will be submitted for future publication in a medical journal.

Additionally,Merck today announcedit is now enrolling patientsin 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.2In 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.

For more information on these studies,visit ClinicalTrials.gov and search identifierNCT01982955 for the Phase Ib/II INSIGHT study,NCT03940703 for the Phase II INSIGHT 2 study or NCT02864992 for the Phase II VISION study.

*Tepotinib is the recommended International Nonproprietary Name (INN) for the MET kinase inhibitor (MSC2156119J). Tepotinib is currently under clinical investigation and not approved for any use anywhere in the world.

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.3 Alterations 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,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.

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About Merck

Merck,operates across healthcare,life science and performance materials. Around 52,000 employees work to make a positive difference to millions of people's lives every day by creating more joyful and sustainable ways to live. From advancing gene editing technologies and discovering unique ways to treat the most challenging diseases to enabling the intelligence of devices – the company is everywhere. In 2018,Merck generated sales of € 14.8 billion in 66 countries.

Scientific exploration and responsible entrepreneurship have been key to Merck's technological and scientific advances. This is how Merck has thrived since its founding in 1668. The founding family remains the majority owner of the publicly listed company. Merck holds the global rights to the Merck name and brand. The only exceptions are the United States and Canada,where the business sectors of Merck operate as EMD Serono in healthcare,MilliporeSigma in life science,and EMD Performance Materials.

References

Yang J,et al. AACR 2019 abstract CT193; NCT01982955.

Paik P,et al. J Clin Oncol 2019;37: (suppl; abstr 9005).

Bray F,et al. CA Cancer J Clin. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 2018;68(6):394–424. https://doi.org/10.3322/caac.21492 PMID:30207593

Reungwetwattana T,et al. Lung Cancer 2017;103:27-37.

Mo HN,et al. Chronic Dis Transl Med 2017; 3(3):148-153.

Lutterbach B,et al. Cancer Res 2007;67:2081–8.

Contact:

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