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June 1, 2015 7:00 am ET

New Data Presented at ASCO in Multiple, Difficult-to-Treat Cancers, including Small Cell Lung, Esophageal and Ovarian Cancers

Registrational Studies for KEYTRUDA Ongoing in Eight Different Tumor Types

KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE: MRK), known as MSD outside the United States and Canada,
today announced the first-time presentation of findings investigating
the use of KEYTRUDA^® (pembrolizumab), the company’s anti-PD-1
therapy, in multiple, difficult-to-treat cancers, including advanced
small cell lung cancer (SCLC), esophageal cancer and ovarian cancer from
the KEYNOTE-028 Phase 1b study. These data, which were presented at the
51^st Annual Meeting of the American Society of Clinical
Oncology (ASCO) in Chicago, May 29 – June 2, 2015, build upon Merck’s
broad and fast-growing immuno-oncology clinical development program for
KEYTRUDA.

“The breadth and depth of the data being shared at ASCO reinforces the
potential for the broad clinical activity that we have seen with
KEYTRUDA in multiple types of cancer,” said Dr. Roy Baynes, senior vice
president and head of global clinical development, Merck Research
Laboratories. “Our goal is to help people with cancer and these data are
furthering our understanding of which patients may be more likely to
benefit from our anti-PD-1 therapy.”

As of ASCO, data presented has demonstrated anti-tumor activity with
KEYTRUDA in 13 different tumor types. Registrational trials are planned
or ongoing in eight different tumor types, as monotherapy and in
combination with other therapies. KEYTRUDA was the first anti-PD-1
therapy approved in the United States and is currently indicated at a
dose of 2 mg/kg administered 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. Please see below for complete indication and selected
safety information for KEYTRUDA.

About the KEYNOTE-028 Phase 1b Study

KEYNOTE-028 is an ongoing multi-cohort, non-randomized Phase 1b basket
trial evaluating the safety, tolerability, and anti-tumor activity of
KEYTRUDA monotherapy (10 mg/kg dosed every two weeks) in more than 450
patients across 20 different types of cancer. The study evaluated
patients with PD-L1 positive advanced solid tumors that have not
responded to current therapy or for which current therapy is not
appropriate.

Early Findings from Advanced Small Cell Lung Cancer Cohort (Abstract
#7502)

These early findings from 20 heavily pre-treated patients with advanced
SCLC, presented on Saturday, May 30 by Dr. Patrick Ott, Dana-Farber
Cancer Institute, demonstrated an overall response rate (ORR) (confirmed
and unconfirmed) of 35 percent (n=7/20) (95% CI, 15-59) (per RECIST
v1.1). At the time of the analysis, six of seven responses were ongoing.
The median follow-up duration for evaluable patients was 21 weeks
(range, 2-48). Adverse events were consistent with previously reported
safety data for KEYTRUDA. Treatment-related adverse events (occurring in
two or more patients) were observed in 14 patients. Grade 3-4
investigator-assessed, treatment-related adverse events were asthenia
(n=1) and blood bilirubin increased (n=1). Some patients experienced
adverse events of special interest, including autoimmune thyroiditis
(n=1, Grade 2) and colitis (n=1, Grade 5). There was one
treatment-related death (colitis).

Early Findings from Advanced Esophageal Cancer Cohort (Abstract #4010)

These early findings from 23 heavily pre-treated patients with advanced
esophageal cancer, presented in a clinical science symposium on Sunday,
May 31 by Dr. Toshihiko Doi, National Cancer Center Hospital East,
Kashiwa, Japan, demonstrated an ORR (confirmed and unconfirmed) of 30.4
percent of patients (n=7/23) (95% CI, 13.2-52.9) (per RECIST v1.1). In
patients with squamous cell carcinoma, the ORR was 29.4 percent (n=5/17)
and in patients with adenocarcinoma, the ORR was 40 percent (n=2/5). The
median duration of response was 40 weeks (0.1+ to 40), with six of seven
responses ongoing. Tumor shrinkage was achieved in 52.2 percent of
evaluable patients. Adverse events were consistent with previously
reported safety data for KEYTRUDA. Treatment-related adverse events
(occurring in two or more patients) were observed in nine patients. All
investigator-assessed, treatment-related adverse events were Grade 3 and
included lymphocyte count decreased (n=2), decreased appetite (n=1),
liver disorder (n=1), and pruritic rash (n=1). Some patients experienced
adverse events of special interest (Grade 2), including hypothyroidism
(n=2) and adrenal insufficiency (n=1). There were no treatment-related
deaths.

Early Findings from Advanced Ovarian Cancer Cohort (Abstract #5510)

These early findings from 26 heavily pre-treated patients with advanced
ovarian cancer, which will be presented in a clinical science symposium
on Monday, June 1 by Dr. Andrea Varga, Gustave Roussy Institute,
Villejuif, France, demonstrated an ORR (confirmed and unconfirmed) of
11.5 percent of patients (n=3/26) (95% CI, 2.4-30.2) (per RECIST v1.1).
Additionally, there was a disease control rate (DCR) of 34.6 percent
(n=9/26) (95% CI, 17.2-55.7). At the time of the analysis, the median
duration of response had not been reached (27.9-36.3). Tumor shrinkage
was achieved in 23 percent of evaluable patients. Adverse events were
consistent with previously reported safety data for KEYTRUDA.
Treatment-related adverse events (occurring in two or more patients)
were observed in 18 patients. One Grade 3-4 treatment-related adverse
event occurred (transaminases increased). Some patients experienced
adverse events of special interest, including hyperthyroidism (n=2),
hypothyroidism (n=3), myositis (n=1) and pancreatitis (n=1). There were
no treatment related deaths.

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.

KEYTRUDA is indicated in the United States at a dose of 2 mg/kg
administered as an intravenous infusion over 30 minutes 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 a broad and fast-growing clinical development program
for KEYTRUDA with more than 100 clinical trials – across more than 30
tumor types and enrolling more than 16,000 patients – both as a
monotherapy and in combination with other therapies.

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
pneumonitis.

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
corticosteroids.

Other clinically important immune-mediated adverse reactions can occur.
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.

For suspected immune-mediated adverse reactions, ensure adequate
evaluation to confirm etiology or exclude other causes. Based on the
severity of the adverse reaction, withhold KEYTRUDA and administer
corticosteroids. Upon improvement of the adverse reaction to Grade 1 or
less, initiate corticosteroid taper and continue to taper over at least
1 month. Restart KEYTRUDA if the adverse reaction remains at Grade 1 or
less. Permanently discontinue KEYTRUDA for any severe or Grade 3
immune-mediated adverse reaction that recurs and for any
life-threatening immune-mediated adverse reaction.

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 the
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 Lung Cancer

Lung cancer, which forms in the tissues of the lungs, usually within
cells lining the air passages, is the leading cause of cancer death
worldwide. The two main types of lung cancer are non-small cell lung
cancer (NSCLC) and small cell lung cancer (SCLC). In 2012, there were an
estimated 1.8 million new cases of lung cancer diagnosed worldwide. SCLC
accounts for about 10-15 percent of all lung cancer cases.

About Esophageal Cancer

Esophageal cancer is a type of cancer that begins in the inner layer
(mucosa) of the esophagus and grows outward. There are two main types of
esophageal cancer: squamous cell carcinoma and adenocarcinoma. In 2012,
there were an estimated 456,000 new cases of esophageal cancer and
400,000 esophageal cancer deaths worldwide, making it the eighth most
common cancer.

About Ovarian Cancer

Ovarian cancer is a type of cancer that begins in the ovaries. There are
three main types of ovarian tumors: epithelial ovarian tumors, ovarian
germ cell tumors, and ovarian stromal tumors. In 2012, there were an
estimated 239,000 new cases of ovarian cancer and 152,000 ovarian cancer
deaths worldwide.

About PD-L1 and PD-L1 Expression

PD-L1, also called programmed death-ligand 1, is a protein expressed on
many types of cells, including some cancer cells. Under normal
conditions, the interaction of PD-L1 with another protein, called
programmed death receptor-1 (PD-1), serves as an important immune system
checkpoint, keeping the immune system in balance and preventing the body
from attacking its own cells when inflammation or an infection is
present. When cancerous tumors express PD-L1, however, they are able to
escape detection and destruction by cytotoxic T-cells – a type of
cancer-killing immune cell – allowing the tumor to survive and grow.
Tumor PD-L1 expression has been observed at varying levels across many
tumor types, including breast, lung and bladder cancer. High levels of
PD-L1 expression are under investigation for potential use as a way to
help identify patients with an enhanced likelihood to respond to certain
immune-based treatment approaches.

Our Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology
medicines to help people with cancer worldwide. At Merck Oncology,
helping people fight cancer is our passion and supporting accessibility
to our cancer medicines is our commitment. Our focus is on pursuing
research in immuno-oncology, and we are accelerating every step in the
journey – from lab to clinic – to potentially bring new hope to people
with cancer. For more information about our oncology clinical trials,
visit www.merck.com/clinicaltrials.

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
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 www.merck.com
and connect with us on Twitter,
Facebook
and YouTube.

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 2014 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 (www.sec.gov).

Please see Prescribing Information for KEYTRUDA (pembrolizumab) at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf
and the Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf.

Merck
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