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


September 29, 2014 4:00 am ET

KEYTRUDA® monotherapy achieved 24 percent overall response rate in patients with PD-L1 positive, advanced bladder (urothelial) cancer

Planned Phase 3 study in advanced bladder cancer to be initiated by the end of 2014

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 urothelial cancer (also known as
bladder cancer). The early findings presented showed a confirmed overall
response rate of 24 percent with KEYTRUDA as monotherapy, as measured by
RECIST v1.1, central review (n= 7/29: 95% CI, 10.3-43.5) including a
complete response rate of 10 percent (3/29). At the time of analysis,
response durations ranged from 16+ to 40+ weeks with six of the seven
responders continuing on therapy. In the ongoing study, 64 percent
(61/95) of patients screened had tumors that were determined to be
positive for PD-L1 expression.

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.
Elizabeth R. Plimack, Fox Chase Cancer Center, Philadelphia, at the
European Society for Medical Oncology (ESMO) 2014 Congress in Madrid,
Spain (ABSTRACT #LBA23).

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.

“Although at this stage the dataset is small, we are encouraged by the
response rate, complete response rate, and the durability of the
response in patients suffering from advanced bladder cancer,” said Dr.
Alise Reicin, vice president, oncology, Merck Research Laboratories. “As
communicated previously, based on these data Merck will initiate a Phase
3 study this year to better understand the potential of KEYTRUDA in
advanced bladder cancer.”

Early findings for investigational use of KEYTRUDA in advanced
bladder 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 bladder cancer whose tumors were determined to be positive for
PD-L1 expression (n=29). 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. The majority of patients
had received one or more prior lines of therapy.

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

  Patients Evaluable for Response (n=29)
          n       Percentage       95% CI
Overall Response Rate (ORR)           7       24.1       10.3 – 43.5
Best overall response
  • Complete response
          3       10.3       2.2 – 27.4
  • Partial response
          4       13.8       3.9 – 31.7
  • Stable disease
          4       13.8       3.9 – 31.7
  • Progressive disease
          14       48.3       29.4 – 67.5
  • No assessment
          4       13.8       3.9 – 31.7

*Analysis cut-off date: August 6, 2014

At six months, 58 percent of patients were alive and median overall
survival was 9.3 months (95% CI, 3.6-NR). Additionally, tumor shrinkage
was achieved in 64 percent of evaluable patients with one post-baseline
treatment scan. Analysis of the relationship between PD-L1 expression
and clinical outcomes is ongoing.

Adverse events were consistent with previously reported safety data for
KEYTRUDA. The most common investigator-assessed, treatment-related
adverse events (occurring in greater than or equal to two patients)
included fatigue (18%), peripheral edema (12%), and nausea (9%). Grade
3-5 investigator-assessed, treatment-related adverse events occurred in
a total of four patients. One infusion-related reaction was observed and
one patient discontinued KEYTRUDA due to a treatment-related adverse
reaction. There were no treatment-related deaths.

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.

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. 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 Bladder (Urothelial Tract) Cancer

Bladder cancer is the most common form of urothelial cancer, a cancer
that forms in the layer of tissue (also called the urothelium) that
lines the urethra, bladder, ureters, prostate and renal pelvis.1
Among others, risk factors for bladder cancer include smoking, exposure
to certain industrial chemicals in the workplace, race, ethnicity, age,
and gender.2 The incidence of bladder cancer is elevated in
North America, Europe, North Africa, the Middle East, Australia and New
Zealand.3 In 2012, there were an estimated 430,000 new cases
of bladder cancer and 165,000 bladder cancer deaths worldwide.3

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
healthcare through far-reaching policies, programs and partnerships. For
more information, visit
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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
industry conditions and competition; general economic factors, including
interest rate and currency exchange rate fluctuations; the impact of
pharmaceutical industry regulation and healthcare legislation in the
United States and internationally; global trends toward healthcare cost
containment; technological advances, new products and patents attained
by competitors; challenges inherent in new product development,
including obtaining regulatory approval; Merck’s ability to accurately
predict future market conditions; manufacturing difficulties or delays;
financial instability of international economies and sovereign risk;
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 National Cancer Institute. General Information About
Bladder and Other Urothelial Cancers.
Accessed September 23, 2014.

2 American Cancer Society. What are the risk factors
for bladder cancer?
Accessed September 23, 2014.

3 WHO. 5.10 Bladder Cancer. In: Stewart BW, Wild CP,
eds. World Cancer Report 2014. Lyon, France: WHO Press;
2014: 681-695.


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

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