Merck Presents Updated Results for Investigational Therapy Tepotinib Demonstrating Durable Clinical Response in Patients with Advanced NSCLC with METex14 Skipping Mutations

ASCO Abstract #

Tepotinib (MET kinase inhibitor): 9005

Not intended for UK- , Canada- or US-based media

Darmstadt, Germany (ots/PRNewswire) -

- Alterations of the MET signaling pathway are present in 3-5% of
non-small cell lung cancer patients and correlate with poor
prognosis
- New interim data from Phase II VISION study (all lines of
treatment) show tepotinib induced objective responses, as assessed
by independent review, in 50.0% of patients identified by liquid
biopsy (LBx) and 45.1% of patients identified by tissue biopsy
(TBx)
- Median duration of response was 12.4 months for LBx-identified
patients and 15.7 months for TBx-identified patients
- Safety results for tepotinib are consistent with those reported in
previous studies; most treatment-related adverse events (TRAEs)
were Grade 1 and 2, and no Grade 4 or 5 TRAEs were observed

Merck, a leading science and technology company, today presented
updated results from the potentially registrational Phase II VISION
study, showing durable anti-tumor clinical activity for the
investigational targeted therapy tepotinib* across different lines of
treatment in advanced non-small cell lung cancer (NSCLC) patients
harboring MET exon 14 skipping mutations detected by liquid biopsy
(LBx) or tissue biopsy (TBx). Data were shared in an oral
presentation today at the 2019 American Society of Clinical Oncology
(ASCO) Annual Meeting in Chicago, IL, US.

"Tepotinib has been designed to potentially improve outcomes in
aggressive tumors that have a poor prognosis and harbor these
specific alterations," said Luciano Rossetti, Global Head of Research
& Development for the Biopharma business of Merck. "Tepotinib is an
important part of our strategic focus on precision medicine, and both
the proportion of patients responding and the duration of anti-tumor
clinical activity demonstrate the potential of this investigational
therapy."

Discovered in-house at Merck, tepotinib is an investigational,
highly potent and selective1 oral MET kinase inhibitor that is
designed to inhibit the oncogenic signaling caused by MET (gene)
alterations, including both MET exon 14 skipping mutations and MET
amplifications, or MET protein overexpression. Alterations of the MET
signaling pathway are found in various cancer types, including 3-5%
of NSCLC cases, and correlate with aggressive tumor behavior and poor
clinical prognosis.2-4

"Patients with this NSCLC molecular subtype lack treatment options
that have the potential to significantly improve clinical outcomes,"
said Paul K. Paik, M.D., primary study investigator and Clinical
Director, Thoracic Oncology Service, Memorial Sloan Kettering Cancer
Center. "It is noteworthy to see data that are consistent with
tepotinib's previously reported efficacy findings in this patient
population, and that also provide valuable new insight into its
durable clinical activity across various treatment lines."

Results from the ongoing Phase II VISION study in 73
efficacy-evaluable patients with NSCLC with MET exon 14 skipping
mutations identified by LBx or TBx demonstrate overall objective
response rate (ORR) of 50.0% for LBx-identified patients as assessed
by Independent Review Committee (IRC), and 55.3% as assessed by
investigators. The ORR for TBx-identified patients was 45.1% and
54.9%, respectively. The overall median duration of response (DOR)
was 12.4 months and 17.1 months among LBx-identified patients, as
assessed by IRC and investigators, respectively, while among
TBx-identified patients, 15.7 and 14.3 months were observed,
respectively.

Most treatment-related adverse events (TRAEs) were Grade 1 and 2.
No Grade 4 or 5 TRAEs were observed. Any grade TRAEs reported by
>=10% of 87 patients evaluable for safety were peripheral edema
(48.3%), nausea (23.0%) diarrhea (20.7%) and increased blood
creatinine (12.6%). Other relevant TRAEs of any grade include
increased lipase (4.6%), fatigue (3.4%) and vomiting (3.4%). TRAEs
led to permanent discontinuation in four patients (two patients due
to peripheral edema, one due to interstitial lung disease, one due to
diarrhea and nausea).

The use of both liquid and tissue biopsies to identify patients
for the VISION trial is intended to support improved patient
selection and is consistent with the company's focus on
patient-centric drug development.

Tepotinib is currently being investigated in NSCLC in two
different settings: in NSCLC harboring MET alterations (MET exon 14
skipping mutations and MET amplifications) as monotherapy, as well as
in combination with the tyrosine kinase inhibitor (TKI) osimertinib
in epidermal growth factor receptor (EGFR) mutated MET amplified
NSCLC having acquired resistance to prior EGFR TKI. Additional
information on these clinical trials can be found at
ClinicalTrials.gov using the identifiers NCT02864992 and NCT03940703,
respectively. Merck is also actively assessing the potential of
investigating tepotinib in combination with novel therapies for other
tumor indications.

*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.

Notes to Editors

Tepotinib oral session:

Title Lead Abstract Presentation Location
Author # Date / Time
(CDT)
Tepotinib
Oral
Session
Phase II P.K. 9005 Mon, Jun 3, Hall B1
study of Paik 8:00 AM -
tepotinib 11:00 AM
in NSCLC (9:24 AM -
patients 9:36 AM
with MET lecture
ex14 time)
mutations

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.5 Alterations of the MET signaling
pathway, including MET exon 14 skipping mutations and MET
amplifications, occur in 3-5% of NSCLC cases.2-4

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 mutations 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.

All Merck press releases are distributed by e-mail at the same
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About Merck

Merck, a leading science and technology company, 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 - Merck is everywhere. In 2018, Merck generated sales of
EUR 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

1. Bladt, F et al. Clin Cancer Res 2013;19:2941-2951.
2. Reungwetwattana T, et al. Lung Cancer 2017;103:27-37.
3. Mo HN, et al. Chronic Dis Transl Med 2017; 3(3):148-153.
4. Lutterbach B, et al. Cancer Res 2007;67:2081-8.
5. 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

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