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

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Key ESMO Abstracts #

BAVENCIO® (avelumab): 1451; 3152; 4174; 4256; 4823; 5113, ERBITUX®
(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®* (avelumab) in combination with
axitinib
- Three-year overall survival data for patients treated first-line
with ERBITUX® (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

Darmstadt, Germany (ots/PRNewswire) - 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®* (avelumab) and
ERBITUX® (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® 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® plus axitinib for first-line
treatment of adult patients with advanced RCC.

ERBITUX® 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® 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 Location
# Date / Time
(CEST)
BAVENCIO® (avelumab)
Poster Discussions
Efficacy and biomarker analysis TK. Choueiri 4823 Sunday, Hall 2 -
of the sarcomatoid subgroup September Pamplona
from the phase 3 JAVELIN Renal 29, 2019, AuditoriumPoster
101 trial of first-line 3:00-4:15 Board No. 910PD
avelumab plus axitinib (A + Ax) PM(3:15 PM
vs sunitinib (S) for advanced lecture
renal cell carcinoma (aRCC) time)
Primary renal tumour shrinkage L. Albiges 4174 Sunday, Hall 2 -
in patients (pts) who did not September Pamplona
undergo cytoreductive 29, 2019, AuditoriumPoster
nephrectomy (CN): subgroup 3:00-3:15 Board No. 908PD
analysis from the phase 3 PM(3:15 PM
JAVELIN Renal 101 trial of lecture
first-line avelumab plus time)
axitinib (A + Ax) vs sunitinib
(S) for advanced renal cell
carcinoma (aRCC)
Poster Sessions
Long-term avelumab treatment in B. Hrinczenko 4256 Saturday, Hall 4 - Poster
patients with advanced September AreaPoster Board
non-small cell lung cancer 28, 2019, No. 1493P
(NSCLC): post-hoc analysis from 12:00-1:00
JAVELIN Solid Tumor PM
Assessing the impact of F. Barlesi 5113 Saturday, Hall 4 - Poster
subsequent immunotherapy September AreaPoster Board
treatment on overall survival: 28, 2019, No. 1492P
a post-hoc analysis of the 12:00-1:00
phase 3 JAVELIN Lung 200 study, PM
2L avelumab vs docetaxel in
patients with platinum-treated
NSCLC
Randomized phase 3 trial of M. Uemura 1451 Monday, Hall 4 - Poster
avelumab + axitinib vs September AreaPoster Board
sunitinib as first-line 30, 2019, No. 956P
treatment for advanced renal 12:00-1:00
cell carcinoma: JAVELIN Renal PM
101 Japanese subgroup analysis
Health-related quality of life SP. D'Angelo 3152 Monday, Hall 4 - Poster
in patients with metastatic September AreaPoster Board
Merkel cell carcinoma receiving 30, 2019, No. 1320P
second-line or later avelumab 12:00-1:00
treatment: 36-month follow-up PM
data
ERBITUX® (cetuximab)
Poster Session
Impact of primary tumor side on S. Qin 4455 Sunday, Hall 4 - Poster
3-year survival outcomes of September Area Poster
first-line (1L) FOLFOX-4 ± 29, 2019, Board No. 591P
cetuximab in patients with RAS 12:00-1:00
wild-type (wt) metastatic PM
colorectal cancer (mCRC) in the
phase 3 TAILOR trial
The cost of adverse event K. Patterson 1212 Sunday, Hall 4 - Poster
management in patients with RAS September AreaPoster Board
wild-type metastatic colorectal 29, 2019, No. 596P
cancer treated with first-line 12:00-1:00
cetuximab and panitumumab: an PM
Italian healthcare payer
perspective
Non-inferiority on overall S. Kasper 2589 Sunday, Hall 4 - Poster
survival of every- 2-weeks vs September AreaPoster Board
weekly schedule of cetuximab 29, 2019, No. 584P
for the first-line treatment of 12:00-1:00
RAS wild-type metastatic PM
colorectal cancer
Tepotinib
Poster Session
Safety Profile of Tepotinib in T. Decaens 3930 Saturday, Hall 4 -Poster
Patients with Advanced Solid September Area Poster
Tumors: Pooled Analysis of 28, 2019, Board No. 479P
Phase I and II Data 12:00-1:00
PM
Drug-drug interaction profile J. Heuer 5373 Saturday, Hall 4 - Poster
of tepotinib with CYP3A and September AreaPoster Board
P-gp substrates 28, 2019, No. 480P
12:00-1:00
PM
Bioavailability of tepotinib: J. Heuer 5455 Saturday, Hall 4 - Poster
impact of omeprazole and food September AreaPoster Board
28, 2019, No. 481P
12:00-1:00
PM
Combinations
M6620 Oral Session
Randomized Phase 2 Study of ATR PA. 1547LBA60 Friday, Hall 2 -Pamplona
inhibitor M6620 in Combination Konstantinopoulos September Auditorium
with Gemcitabine versus 27, 2019,
Gemcitabine alone in Platinum 4:45-5:00 PM
Resistant High Grade Serous
Ovarian Cancer
(HGSOC)(NCT02595892)
Poster Session
Phase 1b, open-label, J. Strauss 4062 Monday, Hall 4 - Poster
dose-escalation study of M9241 September AreaPoster Board
(NHS-IL12) plus avelumab in 30, 2019, No. 1264P
patients (pts) with advanced 12:00-1:00
solid tumors PM
Avelumab-cetuximab-radiotherapy Y. Tao 4934 Saturday, Hall 5 - Bilbao
versus standards of care in September Auditorium
locally advanced squamous cell 28, 2019, Poster Board No.
carcinoma of head and neck: 8:45-9:45 1118PD
safety phase of randomized AM(9:05 AM
trial GORTEC 2017-01 (REACH) lecture
time)

About BAVENCIO® (avelumab)

BAVENCIO® is a human anti-programmed death ligand-1 (PD-L1)
antibody. BAVENCIO® 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® has been shown to
release the suppression of the T cell-mediated antitumor immune
response in preclinical models.1-3 BAVENCIO® 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®.

BAVENCIO® Approved Indications

In September 2017, the European Commission granted conditional
marketing authorization for BAVENCIO® as a monotherapy for the
treatment of adult patients with metastatic Merkel cell carcinoma
(mMCC). BAVENCIO® 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® (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® 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® Safety Profile from the EU Summary of Product
Characteristics (SmPC)

The special warnings and precautions for use for BAVENCIO® 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® Important Safety Information from the US FDA-Approved
Label

The warnings and precautions for avelumab (BAVENCIO®) 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 BAVENCIO® 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® 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® (cetuximab)

ERBITUX® is an IgG1 monoclonal antibody targeting the epidermal
growth factor receptor (EGFR). As a monoclonal antibody, the mode of
action of ERBITUX® 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® also targets cytotoxic
immune effector cells towards EGFR expressing tumor cells (antibody
dependent cell-mediated cytotoxicity, ADCC).

Very commonly reported side effects with ERBITUX® include
acne-like skin rash, mild to moderate infusion-related reactions and
hypomagnesemia.

ERBITUX® 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®, 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

Phone: +49 6151 72 26560

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