Merck KGaA, Darmstadt, Germany Presents Update on Tepotinib in Advanced Lung Cancer at ASCO 2018

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Jun 03, 2018, 08:30 ET

DARMSTADT, Germany, June 3, 2018 /PRNewswire/ --

Not intended for UK-based media

ASCO Abstract #
Tepotinib (c-Met kinase inhibitor): 9082, 9016; M7824 (TGF-ß trap/anti-PD-L1): 3007, 9017, 2566; M2698 (dual p70S6k/Akt inhibitor): 2584; M6620 (ATR inhibitor): 2549; M3814 (DNA-PK):2518

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

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 Japan.

"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 non-small 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.

   
                                              Presentation Date
    Title             Lead Author Abstract #  / Time (CDT)         Location

    Tepotinib
    Poster Sessions
    Can duration of
    response be used
    as a surrogate
    endpoint for
    overall survival
    in advanced
    non-small cell    Boris M                 Sun, Jun 03, 8:00
    lung cancer?      Pfeiffer    9082        a.m. - 11:30 a.m.    Hall A
    Poster Discussion
    Tepotinib in
    patients with
    advanced
    non-small cell
    lung cancer
    (NSCLC) harboring
    MET exon
    14-skipping
     mutations: Phase  Enriqueta               Sun, Jun 03, 11:30  
    II trial.         Felip, M.D. 9016        a.m. - 12:45 p.m.    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^]

About Tepotinib

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.

About SAKIGAKE

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.

All Merck KGaA, Darmstadt, Germany, press releases are distributed by e-mail at the same time they become available on the EMD Group Website. In case you are a resident of the USA or Canada please go to http://www.emdgroup.com/subscribe to register again for your online subscription of this service as our newly introduced geo-targeting requires new links in the email. You may later change your selection or discontinue this service.

About Merck KGaA, Darmstadt, Germany

Merck KGaA, Darmstadt, Germany, is a leading science and technology company in healthcare, life science 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.

References

American Cancer Society (2015) Global facts & figures third edition. Available from: http://www.cancer.org/acs/groups/content/@research/documents/document/acspc-044738.pdf. Accessed February 2018
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.
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-lung-cancer.html. Accessed February 2018.
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.
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.
Wong MCS, et al. Incidence and mortality of lung cancer: global trends and association with socioeconomic status. Sci. Rep. (2017) 7:143000: doi: 10.1038/s41598-017-14513-7.