New Findings Show Anti-Tumor Activity of KEYTRUDA® (pembrolizumab) in Patients with Advanced Nasopharyngeal Carcinoma

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September 26, 2015 6:00 am ET

KEYTRUDA Monotherapy Achieved Overall Response Rate of 22.2 Percent in Previously-Treated Patients

Results from KEYNOTE-028 Presented at 2015 European Cancer Congress

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, as a monotherapy in patients with advanced unresectable
nasopharyngeal carcinoma (NPC) – a type of head and neck cancer – whose
tumors express PD-L1 (≥1% of cells in tumor nests or PD-L1+ bands in
stroma). Data were from a Phase 1b study (KEYNOTE-028) and showed an
overall response rate (ORR) (confirmed and unconfirmed) of 22.2 percent
(95% CI, 8.6-42.3) in evaluable patients (n=27) who were treated with
KEYTRUDA. Results were presented in an oral session by Dr. Chiun Hsu,
National Taiwan University Hospital, at the European Cancer Congress
(ECC) in Vienna (Abstract #2801).

“Advanced nasopharyngeal carcinoma is a severe form of head and neck
cancer often associated with a poor prognosis,” said Dr. Hsu. “These
data presented at ECC represent the potential for new approaches to
treat this type of cancer, for which there are currently limited
treatment options, and further support the need for additional research
into how KEYTRUDA may work for certain types of head and neck cancer.”

Merck has initiated a comprehensive clinical development program
evaluating KEYTRUDA in head and neck cancer across multiple lines of
therapy as monotherapy and in combination with chemotherapy as well as
other agents. In KEYNOTE-028, KEYTRUDA is being evaluated in patients
with advanced unresectable NPC that is not responding to current therapy
or for which current therapy is not appropriate. This is the second
study to show early activity of KEYTRUDA in patients with head and neck
cancer and the first study of an anti-PD-1 therapy to demonstrate
clinical activity in patients with recurrent or metastatic NPC. For more
information about our oncology clinical trials, visit www.keynoteclinicaltrials.com.

“The findings emerging from this trial again demonstrate that KEYTRUDA
is active across a broad range of cancers, including those that are
difficult to treat with standard treatments,” said Dr. Roger Dansey,
senior vice president and therapeutic area head, oncology late-stage
development, Merck Research Laboratories. “Based on these and other
results to date, we are continuing to advance a comprehensive head and
neck clinical program for KEYTRUDA, and we remain focused on realizing
its full potential to address the unmet treatment needs for patients
with difficult-to-treat cancers such as nasopharyngeal carcinoma.”

Additional Nasopharyngeal Carcinoma Results from KEYNOTE-028

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) 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.

These early findings from 27 heavily pre-treated patients with advanced
NPC demonstrated an ORR of 22.2 percent (n=6/27) (per RECIST v1.1),
including six partial responses (95% CI, 8.6-42.3). Additionally, 55.6
percent of patients had stable disease (n=15/27) (95% CI, 35.3-74.5),
the disease control rate (DCR) was 77.8 percent (n=21/27) (95% CI,
57.7-91.4), and tumor shrinkage was achieved in 67 percent of patients.
The 6-month progression-free survival (PFS) rate was 49.7 percent and
the 12-month PFS rate was 28.9 percent. The median follow-up duration
for evaluable patients was 12.9 months (range, 2.2−15.0) and the median
response duration was 10.8 months (range, 4.8- 10.8).

Adverse events were generally consistent with previously reported safety
data for KEYTRUDA. Grade 3-5 investigator-assessed, treatment-related
adverse events were hepatitis (n=2), pneumonitis (n=2), anemia (n=1),
facial pain (n=1), increased blood creatine phosphokinase (n=1),
proteinuria (n=1), and sepsis (n=1). Immune-mediated adverse events were
hypothyroidism (n=5), hepatitis (n=4), and pneumonitis (n=3). There was
one treatment-related death due to bacterial sepsis.

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, bladder cancer, and nasopharyngeal
carcinoma. High levels of PD-L1 expression, called overexpression, 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.

About Nasopharyngeal Cancer

Nasopharyngeal cancer (NPC) is a type of head and neck cancer that
starts in the epithelial cells that line the surface of the nasopharynx,
the upper part of the throat behind the nose and near the base of skull.¹
There are three types of NPC, based on how the cancer cells look under
the microscope: keratinizing squamous cell carcinoma, non-keratinizing
differentiated carcinoma, and undifferentiated carcinoma.¹
Leading risk factors for NPC include Chinese or Asian ancestry, being
exposed to the Epstein-Barr virus, and drinking large amounts of alcohol.²
In most parts of the world (including the United States), there is less
than one case of NPC for every 100,000 people each year.³ In
2015, about 3,200 cases of NPC are expected to occur in the United
States.³

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.

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, NSCLC, head and neck cancer, bladder
cancer, gastric cancer, colorectal cancer, and Hodgkin Lymphoma, with
further trials in planning for other cancers.

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
and connect with us on Twitter,
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and YouTube.

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 s
patents and other protections for innovative products; and the exposure
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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
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References

1. http://www.cancer.org/cancer/nasopharyngealcancer/detailedguide/nasopharyngeal-cancer-what-is-nasopharyngeal-cancer

2. http://www.cancer.gov/types/head-and-neck/patient/nasopharyngeal-treatment-pdq

3. http://www.cancer.org/cancer/nasopharyngealcancer/detailedguide/nasopharyngeal-cancer-key-statistics

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.