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
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 cancer."
“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,
2015.
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 papillomaviruses. 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 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.
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.
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908-200-1889orInvestors:Joseph Romanelli, 908-740-1986Justin Holko,
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