New Findings Show Durable Anti-Tumor Activity with KEYTRUDA® (pembrolizumab), Merck’s Anti-PD-1 Therapy, in Patients with Advanced Head and Neck Cancer, Regardless of PD-L1 Expression Status


May 29, 2015 1:06 pm ET

Results from KEYNOTE-012, the First and Largest Study to Date of an Anti-PD-1 Therapy in Head and Neck Cancer, to be Presented at 2015 ASCO Annual Meeting

KEYTRUDA Monotherapy Achieved Overall Response Rate of 25 Percent in Heavily Pre-treated Patients

Merck is Advancing a Broad Head and Neck Clinical Program for KEYTRUDA with Five Clinical Trials, Across Multiple Lines of Therapy and in Combination with Other Agents

KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced new investigational data evaluating KEYTRUDA®
(pembrolizumab), the company’s anti-PD-1 therapy, as a monotherapy from
the KEYNOTE-012 Phase 1b study in 132 pre-treated patients with
recurrent or metastatic head and neck cancer, regardless of PD-L1
expression status. In the evaluable patients, the overall response rate
(ORR) (confirmed and unconfirmed) was 24.8 percent for KEYTRUDA (200 mg
fixed dose every three weeks) (n=29/117) (95% CI, 17.3-33.6). When
looking at HPV status, the ORR was similar among HPV-positive and
HPV-negative disease (20.6 percent [n=7/34] and 27.2 percent [n=22/81],
respectively) (95% CI, 8.7-37.9 and 17.9-38.2). These data, featured in
the ASCO Press Program today, will be presented in an oral session by
Dr. Tanguy Seiwert, The University of Chicago, on Monday, June 1 at the
51st Annual Meeting of the American Society of Clinical
Oncology (ASCO) in Chicago (Abstract #LBA6008).

Merck has initiated a comprehensive clinical development program for
KEYTRUDA evaluating a fixed dosing regimen (200 mg every three weeks) in
head and neck cancer across multiple lines of therapy as monotherapy and
in combination with chemotherapy and other agents. Results from
KEYNOTE-012 were first presented at the 2014 ASCO Annual Meeting and
showed 19.6 percent ORR for KEYTRUDA (10 mg/kg every two weeks) in
heavily pre-treated patients with advanced head and neck cancer with
tumor cells positive for PD-L1 expression.

“Advanced head and neck cancer is a severe and life-altering condition.
Unfortunately we have few effective treatment options, particularly for
patients whose disease is not responding to current therapies,” said Dr.
Seiwert. “As a practicing oncologist, I am very encouraged by the
durable responses demonstrated with pembrolizumab in this study, and
look forward to data being shared in the future from the additional
confirmatory studies now being conducted in advanced head and neck

“The totality of the data presented at ASCO furthers our understanding
of the clinical potential of KEYTRUDA in head and neck cancer,
regardless of PD-L1 expression or HPV status,” said Dr. Roger Dansey,
senior vice president and therapeutic area head, oncology late-stage
development, Merck Research Laboratories. “Based on the results observed
to date, we are advancing multiple registrational studies in head and
neck cancer including randomized evaluations of overall survival and
progression-free survival with KEYTRUDA, as monotherapy and in
combination with chemotherapy, compared to standard of care.”

Additional Results from KEYNOTE-012 in Advanced Head and Neck Cancer

Additional findings from KEYNOTE-012, the first and largest Phase 1b
study of an anti-PD-1 therapy in advanced head and neck cancer, showed
tumor shrinkage was achieved in 56 percent of total evaluable patients
who had measurable disease with one post baseline scan (n=59/106). The
median duration of response was not reached (7.3+ – 25.1+ weeks among
patients with a confirmed response), with a median follow up duration of
5.7 months (0.2 – 8.7 months). At the time of the analysis, 86 percent
of patients who responded continued to respond to treatment (n=25/29).
The data are based on an analysis conducted with a cut-off of March 23,

Adverse events in the study were consistent with previously reported
safety data for KEYTRUDA (n=132). The most common treatment-related
adverse events (occurring in greater than or equal to 5% of patients)
included: fatigue (15.2%), hypothyroidism (9.1%), decreased appetite
(7.6%), rash (7.6%), dry skin (6.8%), and pyrexia (6.8%). Some patients
experienced adverse events of special interest, including hypothyroidism
(10.6%), pneumonitis (3.0%), thyroiditis (2.3%), colitis (0.8%),
interstitial lung disease (0.8%), acquired epidermolysis bullosa (0.8%),
drug induced liver injury (0.8%), epidermolysis (0.8%), and diabetic
ketoacidosis (0.8%). Four patients experienced adverse events of special
interest that resulted in treatment discontinuation. 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 (10 mg/kg every two weeks or 200 mg IV every three weeks) in
patients with advanced triple negative breast cancer (TNBC), advanced
head and neck cancer, advanced urothelial 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);
secondary endpoints include progression-free survival (PFS), overall
survival (OS), and duration of response.

About Head and Neck Cancer

Head and neck cancer describes a number of different tumors that develop
in or around the throat, larynx, nose, sinuses and mouth. Most head and
neck cancers are squamous cell carcinomas that begin in the flat,
squamous cells that make up the thin surface layer of the structures in
the head and neck. The leading modifiable risk factors for head and neck
cancer include tobacco and heavy alcohol use. Other non-modifiable risk
factors include infection with certain types of HPV, also called human
. Each year there are approximately 400,000 cases of
cancer of the oral cavity and pharynx, in addition to approximately
160,000 cancers of the larynx, resulting in approximately 300,000 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

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

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.

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,

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
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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
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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 (

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

Pamela Eisele, 267-664-0282
Claire Mulhearn, 908-200-1889
Joseph Romanelli, 908-740-1986
Justin Holko, 908-740-1879

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