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

PR79057

DARMSTADT, Germany , June 4, 2019 /PRNewswire=KYODO JBN/ --

ASCO Abstract #

Tepotinib (MET kinase inhibitor): 9005

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

*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 greater or equal to 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: Tepotinib Oral Session: Phase II study of tepotinib in NSCLC patients

with METex14 mutations

Lead Author:  P.K. Paik

Abstract #: 9005

Presentation Date / Time (CDT): Mon, Jun 3, 8:00 AM ¡§C 11:00 AM (9:24 AM ¡§C

9:36 AM lecture time)

Location: Hall B1

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 time they become

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register online, change your selection or discontinue this service.

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 ¡§C Merck is everywhere. In 2018, Merck generated

sales of Euro 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¡§C8.

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¡§C424. https://doi.org/10.3322/caac.21492 PMID:30207593

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Source: Merck