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September 27, 2015 6:00 am ET

Findings Show Anti-Tumor Activity for KEYTRUDA in Two Gastrointestinal Cancers

KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced new findings from the KEYNOTE-028 Phase 1b study, the
clinical trial investigating the use of the company’s anti-PD-1 therapy,
KEYTRUDA^® (pembrolizumab) in multiple, difficult-to-treat
cancers. Data from this trial, to be presented at the European Cancer
Congress (ECC) in Vienna, Austria, Sept. 25-29, include the first-time
findings for KEYTRUDA in two gastrointestinal cancers, advanced anal
cancer and advanced biliary tract cancer, and add to Merck’s growing
body of clinical data for KEYTRUDA.

KEYNOTE-028 is an ongoing multi-cohort, non-randomized Phase 1b basket
trial – a trial design that allows for the study of multiple
sub-populations of different tumor or histological types within one
study. The study is 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
was designed to evaluate patients with advanced solid tumors that
express PD-L1 and which have not responded to current therapy or for
which current therapy is not appropriate.

“Through innovative trials like KEYNOTE-028, we are advancing our
understanding of the potential benefit of KEYTRUDA in a wide range of
difficult-to-treat cancers,” said Dr. Roger Dansey, senior vice
president and therapeutic area head, oncology late-stage development,
Merck Research Laboratories. “Merck is committed to evaluating KEYTRUDA
across as many tumor types as possible and the expansion of our clinical
development program over the years reflects this. We are encouraged by
these early stage data, and will continue to advance KEYTRUDA in order
to deliver on our goal of helping as many people with cancer as
possible.”

The KEYTRUDA clinical development program has rapidly expanded to
encompass more than 30 tumor types in more than 130 clinical trials, of
which more than 70 trials combine KEYTRUDA with other cancer treatments.
Registration-enabling trials of KEYTRUDA monotherapy are currently
enrolling patients in melanoma, non-small cell lung cancer (NSCLC), head
and neck cancer, bladder cancer, gastric cancer, colorectal cancer, and
Hodgkin Lymphoma, with further trials in planning for other cancers.

Early Findings from Advanced Squamous Cell Carcinoma (SCC) of the
Anal Canal (Abstract #500)

Early findings from 25 heavily pre-treated patients with advanced anal
cancer – to be presented in an oral session on Sunday, Sept. 27 by Dr.
Patrick Ott, Dana-Farber Cancer Institute – demonstrated an overall
response rate (ORR) of 20 percent (confirmed and unconfirmed) (95% CI,
6.8-40.7) and a disease control rate (DCR) of 64 percent (95% CI,
42.5-82.0). Five partial responses (95% CI, 6.8-40.7) were observed, and
44 percent of patients (n=11/25) had stable disease (95% CI, 24.4-65.1).
Additionally, the 6-month progression-free survival (PFS) rate was 31.6
percent and the 12-month PFS rate was 19.7 percent. At the time of the
analysis, response duration ranged from 0.1+ to 9.2+ months, with the
median not yet reached. The median stable disease duration was 3.6
months (range, 1.8+ to 11.0+).

Adverse events were generally consistent with previously reported safety
data for KEYTRUDA. Grade 3-4 investigator-assessed, treatment-related
adverse events were thyroid-stimulating hormone increased (n=1), colitis
(n=1), diarrhea (n=1), and general physical health deterioration (n=1).
Immune-mediated adverse events were hypothyroidism (n=3) and colitis
(n=1). There were no treatment-related deaths.

Early Findings from Advanced Biliary Tract Cancer (Abstract #525)

Early findings from 24 heavily pre-treated patients with advanced
biliary tract cancer – presented in a poster session on Saturday, Sept.
26 by Dr. Yung-Jue Bang, Seoul National University Hospital, Seoul,
Korea – demonstrated an ORR of 17.4 percent (confirmed and unconfirmed)
(95% CI, 5.0-38.8) (n=4/23); 17.4 percent of patients had stable disease
(95% CI, 5.0-38.8) (n=4/23). As the time of the analysis, three of four
responses were ongoing, and the median response duration had not yet
been reached (range, 5.4+ to 9.3+ weeks).

Adverse events were generally consistent with previously reported safety
data for KEYTRUDA. Grade 3-4 investigator-assessed, treatment-related
adverse events were anemia (n=1), autoimmune hemolytic anemia (n=1),
colitis (n=1) and dermatitis (n=1). Immune-mediated adverse events were
autoimmune hemolytic anemia (n=1), colitis (n=1), hypothyroidism (n=1),
and hypothyroidism (n=1). There were no treatment-related deaths.

About KEYTRUDA^® (pembrolizumab)

KEYTRUDA 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 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.

Selected Important Safety Information for KEYTRUDA

Pneumonitis occurred in 12 (2.9%) of 411 patients, including Grade 2 or
3 cases in 8 (1.9%) and 1 (0.2%) patients, respectively, receiving
KEYTRUDA. 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 patients for signs and symptoms of hypophysitis
(including hypopituitarism and adrenal insufficiency). 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.

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.

Type 1 diabetes mellitus, including diabetic ketoacidosis, has occurred
in patients receiving KEYTRUDA. Monitor patients for hyperglycemia and
other signs and symptoms of diabetes. Administer insulin for type 1
diabetes, and withhold KEYTRUDA in cases of severe hyperglycemia until
metabolic control is achieved.

Nephritis occurred in 3 (0.7%) patients, 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.

Other clinically important immune-mediated adverse reactions can occur.
The following clinically significant immune-mediated adverse reactions
occurred in patients treated with KEYTRUDA: exfoliative dermatitis,
uveitis, arthritis, myositis, pancreatitis, hemolytic anemia, partial
seizures arising in a patient with inflammatory foci in brain
parenchyma, severe dermatitis including bullous pemphigoid, 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.

Infusion-related reactions, including severe and life-threatening
reactions, have occurred in patients receiving KEYTRUDA. Monitor
patients for signs and symptoms of infusion-related reactions including
rigors, chills, wheezing, pruritus, flushing, rash, hypotension,
hypoxemia, and fever. For severe or life-threatening reactions, stop
infusion and permanently discontinue KEYTRUDA.

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.

KEYTRUDA was discontinued for adverse reactions in 9% of 411 patients.
Adverse reactions, reported in at least two patients, that led to
discontinuation of KEYTRUDA were: pneumonitis, renal failure, and pain.
Serious adverse reactions occurred in 36% of patients. The most frequent
serious adverse reactions, reported in 2% or more of patients, were
renal failure, dyspnea, pneumonia, and cellulitis.

The most common adverse reactions (reported in at least 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.

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
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Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA

This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the
“company”) includes “forward-looking statements” within the meaning of
the safe harbor provisions of the U.S. Private Securities Litigation
Reform Act of 1995. These statements are based upon the current beliefs
and expectations of the company’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; the company’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 the company’s patents
and other protections for innovative products; and the exposure to
litigation, including patent litigation, and/or regulatory actions.

The company 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 the company’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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