New Data at ESMO 2019 for Merck Highlight Focused Clinical Development and Commitment to Patient Care

PR80668

DARMSTADT, Germany, Sept.. 23, 2019, /PRNewswire=KYODO JBN/--

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Key ESMO Abstracts #

BAVENCIO(R)(avelumab): 1451; 3152; 4174; 4256; 4823; 5113,

ERBITUX(R)(cetuximab): 1212, 2589, 4455, Tepotinib (MET kinase inhibitor):

3930; 5373; 5455, M6620 (ATR inhibitor): 1547, Combinations: 4062; 4934.

- New subgroup analyses for first-line treatment of advanced renal cell

  carcinoma with BAVENCIO(R)*  (avelumab) in combination with axitinib

- Three-year overall survival data for patients treated first-line with

  ERBITUX(R)(cetuximab) plus FOLFOX-4 in metastatic colorectal cancer

- Data across several therapeutic agents showcase progress of early- to

  late-stage pipeline, including tepotinib†, and novel combinations

Merck, a leading science and technology company, today announced that new data

representing several key therapeutic agents from its diverse oncology pipeline

will be presented at the 2019 European Society for Medical Oncology (ESMO)

Congress, September 27–October 1, in Barcelona, Spain.

Spanning multiple tumor types, data being presented include new evidence

supporting approved treatments BAVENCIO(R)* (avelumab) and ERBITUX(R)

(cetuximab), and new research from Merck's early pipeline including novel

combinations and the investigational targeted therapy tepotinib†, recently

granted Breakthrough Therapy Designation (BTD) by the US Food and Drug

Administration (FDA) in patients with metastatic non-small cell lung cancer

(NSCLC) harboring MET exon 14 skipping alterations who progressed following

platinum-based cancer therapy. In March 2018, tepotinib's potential was also

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.

"Our presence at ESMO underscores our commitment to research and development in

highly focused areas within immuno-oncology, precision medicine and DNA damage

response," said Luciano Rossetti, Global Head of Research & Development for the

Biopharma business of Merck. "We believe that by applying cutting-edge science

in our clinical programs we are getting closer to making a difference in

patient outcomes."

New data for BAVENCIO(R) will include two poster discussions from the Phase III

JAVELIN Renal 101 study evaluating efficacy of first-line treatment with

avelumab in combination with axitinib compared with sunitinib in two clinically

relevant subgroups of patients with advanced renal cell carcinoma (RCC): those

with sarcomatoid histology and those who did not undergo upfront cytoreductive

nephrectomy. Results from JAVELIN Renal 101 supported the recent US FDA

approval and the positive opinion from the Committee for Medicinal Products for

Human Use (CHMP) of the European Medicines Agency (EMA) for BAVENCIO(R)plus

axitinib for first-line treatment of adult patients with advanced RCC.

BAVENCIO(R)data further reinforce the impact of primary tumor location on

three-year overall survival among patients from China with RAS wild-type

metastatic colorectal cancer (mCRC) treated with first-line FOLFOX-4 with or

without cetuximab from the Phase III TAILOR trial. Additionally, a pooled

analysis of patient-level data explores the effect on overall survival of

cetuximab in combination with chemotherapy dosed once every two weeks, compared

with once-weekly dosing, for first-line treatment in patients with RAS

wild-type mCRC. These two sets of results underscore the clinical benefit of

cetuximab and add to the growing body of evidence supporting its role in

combination with chemotherapy in first-line RAS wild-type mCRC.

New research will be presented from across the company's earlier pipeline,

including a pooled analysis of safety data across Phase I and II studies in

advanced solid tumors for the investigational oral MET inhibitor tepotinib.

A number of investigator-sponsored studies (ISS) and collaborative research

studies (CRS) exploring Merck's pipeline will also be presented at this year's

congress, including a late-breaking oral presentation on results from a

randomized Phase II study of M6620‡, an investigational ataxia telangiectasia

and rad3-related (ATR) kinase inhibitor from the company's comprehensive DNA

Damage Response (DDR) portfolio, in combination with gemcitabine compared with

gemcitabine alone in platinum-resistant high-grade serous ovarian cancer. The

study is sponsored by the National Cancer Institute (NCI) under its Cooperative

Research and Development Agreement with Merck for M6620, and these results are

the first-ever randomized data to be presented for an ATR inhibitor.

*The combination of BAVENCIO(R)and axitinib is approved for the first-line

treatment of advanced RCC only in the United States and Argentina. There is no

guarantee that avelumab in combination with axitinib will be approved for RCC

by any other health authority worldwide.

†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.

‡M6620 is currently under clinical investigation and not approved for any use

anywhere in the world.

Notes to Editors

Key Merck, ISS and CRS abstracts scheduled for presentation are listed below.

Title

Lead Author

Abstract #

Presentation

Date / Time

(CEST)

Location

BAVENCIO(R)(avelumab)

Poster Discussions

Efficacy and biomarker analysis of the sarcomatoid subgroup from the phase 3

JAVELIN Renal 101 trial of first-line avelumab plus axitinib (A + Ax) vs

sunitinib (S) for advanced renal cell carcinoma (aRCC)

TK. Choueiri

4823

Sunday,

September 29,

2019, 3:00–4:15

PM

(3:15 PM lecture

time)

Hall 2 – Pamplona Auditorium

Poster Board No. 910PD

Primary renal tumour shrinkage in patients (pts) who did not undergo

cytoreductive nephrectomy (CN): subgroup analysis from the phase 3 JAVELIN

Renal 101 trial of first-line avelumab plus axitinib (A + Ax) vs sunitinib (S)

for advanced renal cell carcinoma (aRCC)

L. Albiges

4174

Sunday, September 29, 2019, 3:00–3:15 PM

(3:15 PM lecture time)

Hall 2 – Pamplona Auditorium

Poster Board No. 908PD

Poster Sessions

Long-term avelumab treatment in patients with advanced non-small cell lung

cancer (NSCLC): post-hoc analysis from JAVELIN Solid Tumor

B. Hrinczenko

4256

Saturday, September 28, 2019, 12:00–1:00 PM

Hall 4 - Poster Area

Poster Board No. 1493P

Assessing the impact of subsequent immunotherapy treatment on overall survival:

a post-hoc analysis of the phase 3 JAVELIN Lung 200 study, 2L avelumab vs

docetaxel in patients with platinum-treated NSCLC

F. Barlesi

5113

Saturday, September 28, 2019, 12:00–1:00 PM

Hall 4 – Poster Area

Poster Board No. 1492P

Randomized phase 3 trial of avelumab + axitinib vs sunitinib as first-line

treatment for advanced renal cell carcinoma: JAVELIN Renal 101 Japanese

subgroup analysis

M. Uemura

1451

Monday, September 30, 2019, 12:00–1:00 PM

Hall 4 – Poster Area

Poster Board No. 956P

Health-related quality of life in patients with metastatic Merkel cell

carcinoma receiving second-line or later avelumab treatment: 36-month follow-up

data

SP. D'Angelo

3152

Monday, September 30, 2019, 12:00–1:00 PM

Hall 4 –

Poster Area

Poster Board No. 1320P

ERBITUX(R)(cetuximab)

Poster Session

Impact of primary tumor side on 3-year survival outcomes of first-line (1L)

FOLFOX-4 ± cetuximab in patients with RAS wild-type (wt) metastatic colorectal

cancer (mCRC) in the phase 3 TAILOR trial

S. Qin

4455

Sunday, September 29, 2019,

12:00–1:00 PM

Hall 4 – Poster Area

Poster Board No. 591P

The cost of adverse event management in patients with RAS wild-type metastatic

colorectal cancer treated with first-line cetuximab and panitumumab: an Italian

healthcare payer perspective

K. Patterson

1212

Sunday, September 29, 2019, 12:00–1:00 PM

Hall 4 – Poster Area

Poster Board No. 596P

Non-inferiority on overall survival of every- 2-weeks vs weekly schedule of

cetuximab for the first-line treatment of RAS wild-type metastatic colorectal

cancer

S. Kasper

2589

Sunday, September 29, 2019, 12:00–1:00 PM

Hall 4 – Poster Area

Poster Board No. 584P

Tepotinib

Poster Session

Safety Profile of Tepotinib in Patients with Advanced Solid Tumors: Pooled

Analysis of Phase I and II Data

T. Decaens

3930

Saturday, September 28, 2019, 12:00–1:00 PM

Hall 4 –Poster Area

Poster Board No. 479P

Drug-drug interaction profile of tepotinib with CYP3A and P-gp substrates

J. Heuer

5373

Saturday, September 28, 2019, 12:00–1:00 PM

Hall 4 – Poster Area

Poster Board No. 480P

Bioavailability of tepotinib: impact of omeprazole and food

J. Heuer

5455

Saturday, September 28, 2019, 12:00–1:00 PM

Hall 4 – Poster Area

Poster Board No. 481P

Combinations

M6620 Oral Session

Randomized Phase 2 Study of ATR inhibitor M6620 in Combination with Gemcitabine

versus Gemcitabine alone in Platinum Resistant High Grade Serous Ovarian Cancer

(HGSOC)

(NCT02595892)

PA. Konstantinopoulos

1547

LBA60

Friday,

September 27, 2019, 4:45–5:00 PM

Hall 2 –

Pamplona Auditorium

Poster Session

Phase 1b, open-label, dose-escalation study of M9241 (NHS-IL12) plus avelumab

in patients (pts) with advanced solid tumors

J. Strauss

4062

Monday, September 30, 2019, 12:00–1:00 PM

Hall 4 – Poster Area

Poster Board No. 1264P

Avelumab-cetuximab-radiotherapy versus standards of care in locally advanced

squamous cell carcinoma of head and neck: safety phase of randomized trial

GORTEC 2017-01 (REACH)

Y. Tao

4934

Saturday, September 28, 2019, 8:45–9:45 AM

(9:05 AM lecture time)

Hall 5 - Bilbao Auditorium

Poster Board No. 1118PD

About ERBITUX(R)(avelumab)

ERBITUX(R)is a human anti-programmed death ligand-1 (PD-L1) antibody.

ERBITUX(R) has been shown in preclinical models to engage both the adaptive and

innate immune functions. By blocking the interaction of PD-L1 with PD-1

receptors, BAVENCIO(R) has been shown to release the suppression of the T

cell-mediated antitumor immune response in preclinical models.1-3

BAVENCIO(R) has also been shown to induce NK cell-mediated direct tumor cell

lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.3-5 In

November 2014, Merck and Pfizer announced a strategic alliance to co-develop

and co-commercialize BAVENCIO(R).

BAVENCIO(R)Approved Indications

In September 2017, the European Commission granted conditional marketing

authorization for BAVENCIO(R)as a monotherapy for the treatment of adult

patients with metastatic Merkel cell carcinoma (mMCC). BAVENCIO(R)is currently

approved for patients with MCC in more than 45 countries globally, with the

majority of these approvals in a broad indication that is not limited to a

specific line of treatment.

In the US, BAVENCIO(R)(avelumab) in combination with axitinib is indicated for

the first-line treatment of patients with advanced renal cell carcinoma (RCC).

Additionally, the US FDA granted accelerated approval for BAVENCIO(R)for the

treatment of (i) adults and pediatric patients 12 years and older with

metastatic Merkel cell carcinoma (mMCC) and (ii) patients with locally advanced

or metastatic urothelial carcinoma (mUC) who have disease progression during or

following platinum-containing chemotherapy, or have disease progression within

12 months of neoadjuvant or adjuvant treatment with platinum-containing

chemotherapy. These indications are approved under accelerated approval based

on tumor response rate and duration of response. Continued approval for these

indications may be contingent upon verification and description of clinical

benefit in confirmatory trials.

BAVENCIO(R)Safety Profile from the EU Summary of Product Characteristics (SmPC)

The special warnings and precautions for use for BAVENCIO(R)include

infusion-related reactions and immune-related adverse reactions (such as

pneumonitis, hepatitis, colitis, endocrinopathies, nephritis and renal

dysfunction, and other adverse reactions).

The SmPC list of the most common adverse reactions in patients with solid

tumors includes fatigue, nausea, diarrhea, decreased appetite, constipation,

infusion-related reactions, and weight loss and vomiting.

BAVENCIO(R) Important Safety Information from the US FDA-Approved Label

The warnings and precautions for avelumab (BAVENCIO(R)) include immune-mediated

adverse reactions (such as pneumonitis and hepatitis, colitis,

endocrinopathies, nephritis and renal dysfunction and other adverse reactions,

infusion-related reactions, hepatotoxicity, major adverse cardiovascular events

(MACE) [which can be severe and have included fatal cases], and embryo-fetal

toxicity.

Common adverse reactions (reported in at least 20% of patients) in patients

treated with BAVENCI(R)include fatigue, musculoskeletal pain, diarrhea, nausea,

infusion-related reaction, peripheral edema, decreased appetite/hypophagia,

urinary tract infection and rash. Common adverse reactions (reported in at

least 20% of patients) in patients receiving BAVENCIO(R) in combination with

axitinib include diarrhea, fatigue, hypertension, musculoskeletal pain, nausea,

mucositis, palmar-plantar erythrodysesthesia, dysphonia, decreased appetite,

hypothyroidism, rash, hepatotoxicity, cough, dyspnea, abdominal pain and

headache. Grade 3-4 clinical chemistry and hematology laboratory value

abnormalities reported in at least 10% of patients across studies include

hyponatremia, lymphopenia, increased gamma-glutamyltransferase, blood

triglycerides increased and lipase increased.

Axitinib Important Safety Information from the US FDA Approved Label

In the study of advanced RCC after failure of one prior systemic therapy, the

warnings and precautions for axitinib include hypertension, including

hypertensive crisis, arterial and venous thrombotic events, hemorrhagic events,

cardiac failure, gastrointestinal perforation and fistula, hypothyroidism,

wound healing complications, reversible posterior leukoencephalopathy syndrome

(RPLS), proteinuria, liver enzyme elevation, hepatic impairment, and fetal harm

during pregnancy.

Common adverse events (reported in at least 20% of patients) in patients

receiving axitinib were diarrhea, hypertension, fatigue, decreased appetite,

nausea, dysphonia, hand-foot syndrome, weight decreased, vomiting, asthenia,

and constipation.

About ERBITUX(R)(cetuximab)

ERBITUX(R)is an IgG1 monoclonal antibody targeting the epidermal growth factor

receptor (EGFR). As a monoclonal antibody, the mode of action of ERBITUX(R) is

distinct from standard non-selective chemotherapy treatments in that it

specifically targets and binds to the EGFR. This binding inhibits the

activation of the receptor and the subsequent signal-transduction pathway,

which results in reducing both the invasion of normal tissues by tumor cells

and the spread of tumors to new sites. It is also believed to inhibit the

ability of tumor cells to repair the damage caused by chemotherapy and

radiotherapy and to inhibit the formation of new blood vessels inside tumors,

which appears to lead to an overall suppression of tumor growth. Based on in

vitro evidence, ERBITUX(R) also targets cytotoxic immune effector cells towards

EGFR expressing tumor cells (antibody dependent cell-mediated cytotoxicity,

ADCC).

Very commonly reported side effects with ERBITUX(R) include acne-like skin

rash, mild to moderate infusion-related reactions and hypomagnesemia.

ERBITUX(R)has already obtained market authorization in over 100 countries

worldwide for the treatment of RAS wild-type metastatic colorectal cancer and

for the treatment of squamous cell carcinoma of the head and neck (SCCHN).

Merck licensed the right to market ERBITUX(R),a registered trademark of ImClone

LLC, outside the U.S. and Canada from ImClone LLC, a wholly-owned subsidiary of

Eli Lilly and Company, in 1998.

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.

References

1.   Dolan DE and Gupta S. Cancer Control 2014;21:231–7.

2.   Dahan R, et al. Cancer Cell 2015;28:285–95.

3.   Boyerinas B, et al. Cancer Immunol Res 2015;3:1148–57.

4.   Kohrt HE, et al. Immunotherapy 2012;4:511–27.

5.   Hamilton G and Rath B. Expert Opin Biol Ther 2017;17:515–23.

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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 – the company 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.

Contact: Annemarie.Eckhardt@merckgroup.com   

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SOURCE: Merck KGaA