Merck Announces First Presentation of Data on the Investigational Use of KEYTRUDA® (pembrolizumab) in Patients with Advanced Gastric Cancer at ESMO 2014


September 28, 2014 2:15 am ET

KEYTRUDA® monotherapy achieved 31 percent overall response rate in patients with PD-L1 positive, advanced gastric cancer

Phase 2 study to be initiated in first quarter of 2015 (KEYNOTE-059)

WHITEHOUSE STATION, N.J.–(BUSINESS WIRE)–Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced the first presentation of data on the investigational
use of KEYTRUDA® (pembrolizumab) – the company’s anti-PD-1
therapy – in PD-L1 positive, advanced gastric cancer. The early findings
presented showed an overall response rate (confirmed and unconfirmed) of
31 percent with KEYTRUDA as monotherapy, as measured by investigator
assessed, RECIST v1.1 (n= 12/39: 95% CI, 17-47). Similar overall
response rates were observed in Asian patients (a population with a high
incidence of gastric cancer) and non-Asian patients. At the time of
analysis, response durations ranged from 8+ to 20+ weeks with 11 of 12
responders continuing on therapy.

These data, from a cohort of the ongoing Phase 1b KEYNOTE-012 study,
were presented today, as part of a late-breaking oral session, by Dr.
Kei Muro, Aichi Cancer Center Hospital, Nagoya, Japan, at the European
Society for Medical Oncology (ESMO) 2014 Congress in Madrid, Spain
(ABSTRACT #LBA15). Data investigating the use of KEYTRUDA monotherapy in
five tumor types will be presented at ESMO 2014.

KEYTRUDA is indicated in the United States at a dose of 2 mg/kg every
three weeks for the treatment of patients with unresectable or
metastatic melanoma and disease progression following ipilimumab and, if
BRAF V600 mutation positive, a BRAF inhibitor. This indication is
approved under accelerated approval based on tumor response rate and
durability of response. An improvement in survival or disease-related
symptoms has not yet been established. Continued approval for this
indication may be contingent upon verification and description of
clinical benefit in the confirmatory trials.

“Merck is advancing the development of KEYTRUDA across different tumor
types and lines of therapy,” said Dr. Alise Reicin, vice president,
oncology, Merck Research Laboratories. “We are encouraged by the signals
of anti-tumor activity in advanced gastric cancer, and are eager to move
ahead with the Phase 2 study to better understand the potential of
KEYTRUDA in advanced gastric cancer.”

Early findings for investigational use of KEYTRUDA in advanced
gastric cancer

Data from a cohort of the ongoing Phase 1b KEYNOTE-012 study evaluated
KEYTRUDA monotherapy at 10 mg/kg every two weeks in patients with
advanced gastric cancer whose tumors were determined to be positive for
PD-L1 expression (n=39). As measured by Merck’s proprietary
immunohistochemistry (IHC) clinical trial assay, tumors were classified
as PD-L1 positive based on greater than or equal to one percent of tumor
cells demonstrating expression of the PD-L1 marker, or any positive
staining with the same reagent in tumor stroma. Enrollment was designed
to include an equal number of Asian and non-Asian patients. The majority
of patients had received two or more prior lines of therapy.

Antitumor activity by Response Evaluation Criteria in Solid Tumors
(RECIST) v1.1*


n = 39


n = 20


n = 19

Overall Response Rate (ORR), % (95% CI) 31 (17-47) 30 (12-54) 31 (12-56)
Disease Control Rate (DCR), % (95% CI) 43 (28-60) 35 (15-59) 52 (29-75)
Best overall response, n (%)
  • Complete response
0 0 0
  • Partial response
12 (31) 6 (30) 6 (32)
  • Stable disease
5 (13) 1 (5) 4 (21)
  • Progressive disease
21 (54) 12 (60) 9 (47)
  • No assessment
1 (2) 1 (5) 0

*Analysis cut-off date: August 6, 2014

Using a prototype assay for PD-L1 assessment, there was evidence of a
preliminary relationship between PD-L1 expression and ORR (P = 0.071)

In the study, tumor shrinkage was demonstrated in 41 percent of
evaluable patients who had measurable disease with one post baseline
scan, per RECIST v1.1 criteria.

Adverse events were consistent with previously reported safety data for
KEYTRUDA. The most common investigator-assessed, treatment-related
adverse events (occurring in greater than five percent) included
hypothyroidism (12.8%) and fatigue (12.8%). Grade 3-5
investigator-assessed, treatment-related adverse events occurred in a
total of three patients, with one patient each in peripheral sensory
neuropathy (Grade 3), hypoxia (Grade 5) and pneumonitis (Grade 4). No
infusion-related reactions were observed and no patients discontinued
KEYTRUDA due to a treatment-related adverse reaction. One
treatment-related death due to hypoxia, as assessed by the investigator,
was reported.

About the KEYNOTE-012 study

KEYNOTE-012 is an ongoing multi-center, non-randomized Phase 1b trial
evaluating the safety, tolerability, and anti-tumor activity of KEYTRUDA
monotherapy in patients with advanced triple negative breast cancer
(TNBC), advanced head and neck cancer, advanced urothelial (bladder)
cancer, or advanced gastric cancer. The primary endpoints of the study
include overall safety, tolerability and anti-tumor activity (as
measured by RECIST v1.1) in PD-L1 positive tumors; secondary endpoints
include progression-free survival (PFS), overall survival (OS) and
duration of response.

Presentation of additional findings investigating the use of KEYTRUDA
in advanced non-small cell lung cancer (NSCLC)

Also presented today, were updated findings in patients with
treatment-naïve or previously treated advanced non-small cell lung
cancer (NSCLC) across cohorts from the ongoing Phase 1b KEYNOTE-001
study (Abstract #LBA43). Data presented in a late-breaking oral session
showed anti-tumor activity [overall response rate (ORR)] with KEYTRUDA
in both treatment-naïve and previously treated patients with advanced
NSCLC (n=236) of 26 and 20 percent, respectively, across all doses and
schedules assessed as measured by independent central review, RECIST
v1.1. Analysis by dose (2 mg/kg every three weeks, 10 mg/kg every three
weeks, and 10 mg/kg every two weeks) showed comparable ORR across dosing
schedules (33 percent, 21 percent, and 21 percent, respectively).

About KEYTRUDA (pembrolizumab)

KEYTRUDA (pembrolizumab) is a humanized monoclonal antibody that blocks
the interaction between PD-1 and its ligands, PD-L1 and PD-L2. By
binding to the PD-1 receptor and blocking the interaction with the
receptor ligands, KEYTRUDA releases the PD-1 pathway-mediated inhibition
of the immune response, including the anti-tumor immune response.

Selected Important Safety Information for KEYTRUDA

Pneumonitis occurred in 12 (2.9%) of 411 patients with advanced melanoma
receiving KEYTRUDA (the approved indication in the United States),
including Grade 2 or 3 cases in 8 (1.9%) and 1 (0.2%) patients,
respectively. Monitor patients for signs and symptoms of pneumonitis.
Evaluate suspected pneumonitis with radiographic imaging. Administer
corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA
for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4

Colitis (including microscopic colitis) occurred in 4 (1%) of 411
patients, including Grade 2 or 3 cases in 1 (0.2%) and 2 (0.5%) patients
respectively, receiving KEYTRUDA. Monitor patients for signs and
symptoms of colitis. Administer corticosteroids for Grade 2 or greater
colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue
KEYTRUDA for Grade 4 colitis.

Hepatitis (including autoimmune hepatitis) occurred in 2 (0.5%) of 411
patients, including a Grade 4 case in 1 (0.2%) patient, receiving
KEYTRUDA. Monitor patients for changes in liver function. Administer
corticosteroids for Grade 2 or greater hepatitis and, based on severity
of liver enzyme elevations, withhold or discontinue KEYTRUDA.

Hypophysitis occurred in 2 (0.5%) of 411 patients, including a Grade 2
case in 1 and a Grade 4 case in 1 (0.2% each) patient, receiving
KEYTRUDA. Monitor for signs and symptoms of hypophysitis. Administer
corticosteroids for Grade 2 or greater hypophysitis. Withhold KEYTRUDA
for Grade 2; withhold or discontinue for Grade 3; and permanently
discontinue KEYTRUDA for Grade 4 hypophysitis.

Nephritis occurred in 3 (0.7%) patients receiving KEYTRUDA, consisting
of one case of Grade 2 autoimmune nephritis (0.2%) and two cases of
interstitial nephritis with renal failure (0.5%), one Grade 3 and one
Grade 4. Monitor patients for changes in renal function. Administer
corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for
Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis.

Hyperthyroidism occurred in 5 (1.2%) of 411 patients, including Grade 2
or 3 cases in 2 (0.5%) and 1 (0.2%) patients respectively, receiving
KEYTRUDA. Hypothyroidism occurred in 34 (8.3%) of 411 patients,
including a Grade 3 case in 1 (0.2%) patient, receiving KEYTRUDA.
Thyroid disorders can occur at any time during treatment. Monitor
patients for changes in thyroid function (at the start of treatment,
periodically during treatment, and as indicated based on clinical
evaluation) and for clinical signs and symptoms of thyroid disorders.
Administer corticosteroids for Grade 3 or greater hyperthyroidism.
Withhold KEYTRUDA for Grade 3; permanently discontinue KEYTRUDA for
Grade 4 hyperthyroidism. Isolated hypothyroidism may be managed with
replacement therapy without treatment interruption and without

The following clinically significant, immune-mediated adverse reactions
occurred in less than 1% of patients treated with KEYTRUDA: exfoliative
dermatitis, uveitis, arthritis, myositis, pancreatitis, hemolytic
anemia, partial seizures arising in a patient with inflammatory foci in
brain parenchyma, adrenal insufficiency, myasthenic syndrome, optic
neuritis, and rhabdomyolysis.

Based on its mechanism of action, KEYTRUDA may cause fetal harm when
administered to a pregnant woman. If used during pregnancy, or if the
patient becomes pregnant during treatment, apprise the patient of
potential hazard to a fetus. Advise females of reproductive potential to
use highly effective contraception during treatment and for 4 months
after the last dose of KEYTRUDA.

For the treatment of advanced melanoma, KEYTRUDA was discontinued for
adverse reactions in 6% of 89 patients who received the recommended dose
of 2 mg/kg and 9% of 411 patients across all doses studied. Serious
adverse reactions occurred in 36% of patients receiving KEYTRUDA
(pembrolizumab). The most frequent serious adverse drug reactions
reported in 2% or more of patients were renal failure, dyspnea,
pneumonia, and cellulitis.

The most common adverse reactions (reported in ≥20% of patients) were
fatigue (47%), cough (30%), nausea (30%), pruritus (30%), rash (29%),
decreased appetite (26%), constipation (21%), arthralgia (20%), and
diarrhea (20%).

The recommended dose of KEYTRUDA is 2 mg/kg administered as an
intravenous infusion over 30 minutes every three weeks until disease
progression or unacceptable toxicity. No formal pharmacokinetic drug
interaction studies have been conducted with KEYTRUDA. It is not known
whether KEYTRUDA is excreted in human milk. Because many drugs are
excreted in human milk, instruct women to discontinue nursing during
treatment with KEYTRUDA. Safety and effectiveness of KEYTRUDA have not
been established in pediatric patients.

About gastric cancer

Gastric cancer, also called stomach cancer, is a type of cancer that
begins in the stomach.1 Most gastric cancers are
adenocarcinomas, which develop from the cells of the innermost lining
(mucosa) of the stomach.1 Among others, risk factors for
gastric cancer include gender, age, ethnicity, geography and bacterial
infection with Helicobacter pylori.1 More than 70
percent of gastric cancer cases occur in developing countries, with half
of all cases occurring in Eastern Asia (predominately China).2
Worldwide, gastric cancer is the fifth most common type of cancer and
the third leading cause of cancer death.2

Our focus on cancer

Our goal is to translate breakthrough science into biomedical
innovations to help people with cancer worldwide. For Merck Oncology,
helping people fight cancer is our passion, supporting accessibility to
our cancer medicines is our commitment, and pursuing research in
immuno-oncology is our focus to potentially bring new hope to people
with cancer. For more information about our oncology clinical trials,

About Merck

Today’s Merck is a global healthcare leader working to help the world be
well. Merck is known as MSD outside the United States and Canada.
Through our prescription medicines, vaccines, biologic therapies, and
consumer care and animal health products, we work with customers and
operate in more than 140 countries to deliver innovative health
solutions. We also demonstrate our commitment to increasing access to
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Forward-Looking Statement

This news release includes “forward-looking statements” within the
meaning of the safe harbor provisions of the United States Private
Securities Litigation Reform Act of 1995. These statements are based
upon the current beliefs and expectations of Merck’s management and are
subject to significant risks and uncertainties. There can be no
guarantees with respect to pipeline products that the products will
receive the necessary regulatory approvals or that they will prove to be
commercially successful. If underlying assumptions prove inaccurate or
risks or uncertainties materialize, actual results may differ materially
from those set forth in the forward-looking statements.

Risks and uncertainties include, but are not limited to, general
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interest rate and currency exchange rate fluctuations; the impact of
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United States and internationally; global trends toward healthcare cost
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by competitors; challenges inherent in new product development,
including obtaining regulatory approval; Merck’s ability to accurately
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dependence on the effectiveness of Merck’s patents and other protections
for innovative products; and the exposure to litigation, including
patent litigation, and/or regulatory actions.

Merck undertakes no obligation to publicly update any forward-looking
statement, whether as a result of new information, future events or
otherwise. Additional factors that could cause results to differ
materially from those described in the forward-looking statements can be
found in Merck’s 2013 Annual Report on Form 10-K and the company’s other
filings with the Securities and Exchange Commission (SEC) available at
the SEC’s Internet site (

Please see Prescribing Information for KEYTRUDA (pembrolizumab) at
and the Medication Guide for KEYTRUDA at

KEYTRUDA® is a registered trademark of Merck
Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

1 American Cancer Society. Stomach Cancer.
Accesses September 17, 2014.

2 World Health Organization. Globocan 2012 Stomach Cancer:
Estimated Incidence, Mortality and Prevalence Worldwide in 2012.
Accessed September 17, 2014.

Ian McConnell, 973-901-5722
Claire Mulhearn, 908-423-7425
Joseph Romanelli, 908-423-5185
Justin Holko, 908-423-5088

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