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Data from an ongoing Phase II tepotinib study show anti-tumor clinical activity in patients with advanced non-small cell lung cancer harboring MET exon 14 skipping mutations
Patients with advanced lung cancer harboring MET exon 14 mutations currently have a poor prognosis and limited treatment options
Safety data are consistent with data previously reported, with no new safety signals identified
ASCO Abstract #
Tepotinib (c-Met kinase inhibitor): 9082, 9016; M7824 (TGF-ß trap/antiPD-L1): 3007, 9017, 2566; M2698 (dual p70S6k/Akt inhibitor): 2584; M6620 (ATR inhibitor): 2549; M3814 (DNA-PK): 2518
Darmstadt, Germany, June 3, 2018 – Merck KGaA, Darmstadt, Germany, a leading science and technology company which operates its healthcare business in the U.S. and Canada as EMD Serono, today announced that the investigational, targeted therapy tepotinib* has shown clinical activity in an ongoing Phase II study of patients with advanced non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping mutations. Data from the VISION trial will be presented during the American Society of Clinical Oncology (ASCO) 2018 Annual Meeting in Chicago, June 1-5, 2018.
“Patients living with advanced non-small cell lung cancer harboring MET exon 14 skipping mutations have limited treatment options available to them and typically face poor clinical outcomes,” said investigator Enriqueta Felip, M.D., Medical Oncologist, Vall d’Hebron Institute of Oncology (VHIO). “More than half of the patients in the Phase II VISION study had an investigator-assessed confirmed response, demonstrating the potential of tepotinib and the need to further evaluate this precision medicine option.”
Initial data from the Phase II VISION study of tepotinib in patients living with advanced NSCLC harboring MET exon 14 skipping mutations will be presented today at ASCO during the “Lung Cancer—Non-Small Cell Metastatic” poster discussion session, 11:30 a.m. – 12:45 p.m. CDT. Treatment with tepotinib led to a confirmed complete response (CR) or confirmed partial response (PR) in 53.6% (15/28) and stable disease (SD) in 17.9% (5/28) of patients based on investigator assessment. Based on independent assessment of updated data from 28 patients (patients with at least 2 post-baseline assessments or who discontinued for any reason), 42.9% (12/28) had a PR and 21.4% (6/28) had SD.
In this ongoing study, the safety data are consistent with that observed in previous studies; no new safety signals have been identified to date. A total of 26 out of 38 patients with data available experienced treatment-related adverse events (TRAEs), most commonly Grade 1/2 peripheral edema (13 patients) and diarrhea (10 patients). Seven patients reported Grade 3 TRAEs, including asymptomatic amylase increase (2 patients) and one instance each of: asthenia, generalized edema, aspartate aminotransferase increase, gamma-glutamyl transferase increase, lipase increase, hyperkalemia, dizziness and pneumonia. Four patients experienced serious TRAEs, with one instance of pneumonia, generalized edema, asthenia and dizziness, and interstitial lung disease. The VISION study is continuing to enroll patients harboring MET exon 14 skipping mutations from Europe, United States and
“These data support our plans to continue with the clinical development of tepotinib in this particularly aggressive, advanced lung cancer. Patients with this form of nonsmall cell lung cancer currently have a poor prognosis and limited treatment options,” said Luciano Rossetti, M.D., Executive Vice President, Global Head of Research & Development at the biopharma business of Merck KGaA, Darmstadt, Germany. “Tepotinib is an important late-stage investigational therapy and a key part of our strategic focus on innovative precision medicines.”
Tepotinib, discovered in-house at Merck KGaA, Darmstadt, Germany, is an investigational inhibitor of the c-Met receptor tyrosine kinase. Alterations of the c-Met signaling pathway are found in various cancer types and correlate with aggressive tumor behavior and poor clinical prognosis. Tepotinib has been designed with the potential to improve outcomes in aggressive tumors that have a poor prognosis and harbor these specific mutations. In March, the Japanese Ministry of Health, Labour and Welfare granted SAKIGAKE ’fast-track’ designation to tepotinib in patients with NSCLC harboring MET exon 14 skipping mutations.
Tepotinib Poster Session
Title: Can duration of response be used as a surrogate endpoint for overall survival in advanced nonsmall cell lung cancer?
Lead Author: Boris M Pfeiffer
Abstract #: 9082
Presentation Date / Time (CDT): Sun, Jun 03, 8:00 a.m. - 11:30 a.m.
Location: Hall A
Tepotinib Poster Discussion
Title: Tepotinib in patients with advanced nonsmall cell lung cancer (NSCLC) harboring MET exon 14-skipping mutations: Phase II trial.
Lead Author: Enriqueta Felip, M.D.
Abstract #: 9016
Presentation Date / Time (CDT): Sun, Jun 03, 11:30 a.m. - 12:45 p.m.
Location: Arie Crown Theater
In addition to tepotinib, Merck KGaA, Darmstadt, Germany, is sharing data from across its oncology and immuno-oncology pipeline at ASCO 2018, including investigational immunotherapy M7824 and updates from its DNA Damage Response portfolio. Merck KGaA, Darmstadt, Germany, is committed to exploring an array of targets and taking creative scientific approaches to developing novel therapies for hard-to-treat cancers.
*Tepotinib is the recommended International Nonproprietary Name (INN) for the c-Met kinase inhibitor (MSC 2156119J). Tepotinib is currently under clinical investigation and not approved for any use anywhere in the world.
About Non-Small Cell Lung Cancer
Globally, lung cancer is the most common cause of cancer-related deaths in men and the second most common in women,1 responsible for more deaths than colon, breast and prostate cancer combined.2 NSCLC is the most common type of lung cancer, accounting for 80 to 85% of all lung cancers.3 MET exon 14 skipping mutations occur in 3-4% of lung cancers.5,6 The five-year survival rate for people diagnosed with lung cancer that has spread (metastasized) to other areas of the body is 1%.4
Tepotinib is an investigational, small-molecule inhibitor of the c-Met receptor tyrosine kinase discovered in-house at Merck KGaA, Darmstadt, Germany. Alterations of the c-Met signaling pathway are found in various cancer types and correlate with aggressive tumor behavior and poor clinical prognosis. Tepotinib is currently being investigated in a Phase II study in NSCLC.
SAKIGAKE designation is granted by the Japanese Ministry of Health, Labour and Welfare, promoting research and development in Japan and aiming at early practical application for innovative pharmaceutical products, medical devices and regenerative medicines. SAKIGAKE designation can reduce a drug’s review period down from 12 months to a target of 6 months. The system’s objective is to designate drugs that have the potential of prominent effectiveness against serious and life-threatening diseases in order to make them available to patients in Japan ahead of the rest of the world.
About Merck KGaA, Darmstadt, Germany
Merck KGaA, Darmstadt, Germany, is a leading science and technology company in healthcare, lifescience and performance materials. Almost 53,000 employees work to further develop technologies that improve and enhance life – from biopharmaceutical therapies to treat cancer or multiple sclerosis, cutting-edge systems for scientific research and production, to liquid crystals for smartphones and LCD televisions. In 2017, Merck KGaA, Darmstadt, Germany, generated sales of € 15.3 billion in 66 countries.
Founded in 1668, Merck KGaA, Darmstadt, Germany, is the world's oldest pharmaceutical and chemical company. The founding family remains the majority owner of the publicly listed corporate group. Merck KGaA, Darmstadt, Germany, holds the global rights to the “Merck” name and brand. The only exceptions are the United States and Canada, where the company operates as EMD Serono, MilliporeSigma and EMD Performance Materials.
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1. American Cancer Society (2015) Global facts & figures third edition. Available from: www.cancer.org/acs/groups/content/@research/documents/document/acspc-044738.pdf. Accessed February 2018
2. American Cancer Society (2017) Key statistics for lung cancer. Available from: https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/key-statistics.html. Accessed February 2018.
3. American Cancer Society (2016) What is non-small cell lung cancer? Available from: https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/what-is-non-small-cell-lungcancer.html. Accessed February 2018.
4. Cancer.net. Lung cancer – non-small cell: statistics. Available from: http://www.cancer.net/cancer-types/lung-cancer-non-small-cell/statistics. Accessed February 2018.
5. Lutterbach B et al. Lung cancer cell lines harboring MET gene amplification are dependent on Met for growth and survival. Cancer Res. (2007) 67(5):2081-8.