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November 12, 2016 11:45 am ET

First Presentation of Data from Phase 3 KEYNOTE-045 Study Presented at the Society for Immunotherapy of Cancer’s (SITC) 31 ^st Annual Meeting

KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced results from the pivotal KEYNOTE-045 study investigating
the use of KEYTRUDA^® (pembrolizumab), the company’s anti-PD-1
therapy, in patients with advanced bladder (urothelial) cancer
previously treated with platinum-containing chemotherapy. As previously
announced, KEYTRUDA was superior to investigator-choice chemotherapy for
the primary endpoint of overall survival (OS) in this phase 3 study, and
was stopped early. Specifically, there was a 27 percent reduction in the
risk of death in patients treated with KEYTRUDA compared to chemotherapy
(OS, HR = 0.73, p-value: 0.0022). Data presented at the Society for
Immunotherapy of Cancer’s (SITC) 31^st Annual Meeting are the
first publicly presented findings from this study.

“The improved overall survival for patients receiving KEYTRUDA in this
trial are clinically significant and could impact how physicians
consider treating patients with previously treated advanced urothelial
cancer,” said Dr. Roger Dansey, senior vice president, oncology
late-stage development, Merck Research Laboratories. “These data add to
the growing body of evidence from our clinical development program for
KEYTRUDA in a range of cancers, including advanced urothelial cancer.”

Study findings are being presented by Dr. Joaquim Bellmunt from
Dana-Farber Cancer Institute on Saturday, Nov. 12^th from
11:45 a.m. – 12:00 p.m. ET (Abstract #470).

“There have been few advancements in the treatment of bladder cancer in
the past several decades, with chemotherapy being the only option,” said
Dr. Dean F. Bajorin, study investigator and medical oncologist at
Memorial Sloan Kettering Cancer Center. “These data demonstrate the
potential for pembrolizumab to provide a meaningful improvement in
overall survival for patients with advanced urothelial cancer who
previously have received platinum-containing chemotherapy.”

The KEYTRUDA (pembrolizumab) clinical development program includes more
than 30 tumor types in more than 360 clinical trials, including nearly
200 trials that combine KEYTRUDA with other cancer treatments.
Currently, Merck has the largest immuno-oncology clinical development
program in bladder cancer, with 27 trials underway involving KEYTRUDA as
monotherapy and in combination, including four registration-enabling
studies.

Findings from KEYNOTE-045

KEYNOTE-045 is a randomized, pivotal, phase 3 study evaluating KEYTRUDA
monotherapy compared to investigator-choice chemotherapy (paclitaxel,
docetaxel, vinflunine) in the treatment of patients with metastatic or
locally advanced, unresectable (inoperable) urothelial cancer
(urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra)
that has recurred or progressed following platinum-based chemotherapy.
The co-primary endpoints are OS and progression-free survival (PFS);
secondary endpoints are overall response rate (ORR), duration of
response, and safety. The study randomized 542 patients to receive
KEYTRUDA (200 mg every three weeks) (n=270) or investigator-choice
chemotherapy (n=272) – either paclitaxel (175 mg/m² every
three weeks), docetaxel (75 mg/m² every three weeks), or
vinflunine (320 mg/m² every three weeks). The study was
designed to assess key endpoints in patients with or without PD-L1
expression (the total study population, n=542), as well as in patients
with PD-L1 expressing tumors (expression of 10% or more) (n=74/270 in
the KEYTRUDA arm; n=90/272 in the chemotherapy arm).

Findings presented at SITC from the total study population showed a
significant improvement in OS with KEYTRUDA compared to chemotherapy,
with a 27 percent reduction in the risk of death (HR: 0.73 [95% CI, 0.59
– 0.91], p-value: 0.0022). Median OS was 10.3 months (95% CI, 8.0 –
11.8) with KEYTRUDA, compared to 7.4 months (95% CI, 6.1 – 8.3) in the
chemotherapy arm. The estimated one-year OS rate was 43.9 percent with
KEYTRUDA, compared to 30.7 percent in the chemotherapy arm.

In the OS analysis of patients with PD-L1 expression, there was a 43
percent reduction in the risk of death with KEYTRUDA, compared to
chemotherapy (HR: 0.57 [95% CI, 0.37 – 0.88], p-value: 0.0048). Median
OS was 8.0 months (95% CI, 5.0 – 12.3) with KEYTRUDA, compared to 5.2
months (95% CI, 4.0 – 7.4) in the chemotherapy arm. The estimated
one-year OS rate was 39.8 percent with KEYTRUDA, compared to 26.9
percent in the chemotherapy arm.

An analysis of the study’s second primary endpoint, PFS, in the total
study population showed a median PFS of 2.1 months (95% CI, 2.0 – 2.2)
with KEYTRUDA, compared to 3.3 months (95% CI, 2.3 – 3.5) in the
chemotherapy arm (HR: 0.98 [95% CI, 0.81 – 1.19], p-value: 0.42). The
six-month PFS rate was 28.8 percent with KEYTRUDA, compared to 26.8 in
the chemotherapy arm; the one-year PFS rate was 16.8 percent with
KEYTRUDA, compared to 6.2 percent in the chemotherapy arm.

The difference in response rates between the two arms was 9.6 percentage
points (p-value: .0011), which was statistically significant and in
favor of KEYTRUDA. The ORR was 21.1 percent with KEYTRUDA (7.0% were
complete responses), compared to 11.4 percent in the chemotherapy arm
(3.3% were complete responses). In patients with PD-L1 expression, ORR
was 21.6 percent with KEYTRUDA (6.8% were complete responses), compared
to 6.7 percent in the chemotherapy arm (2.2% were complete responses).

The median duration of response for patients treated with KEYTRUDA had
not yet been reached at the time of analysis (range: 1.6+ to 15.6+
months) – with 68 percent of responses estimated to last for 12 months
or more. In the chemotherapy arm, the median duration of response was
4.3 months (range: 1.4+ to 15.4+ months) – with 35 percent of responses
estimated to last for 12 months or more.

The safety profile of KEYTRUDA in this trial was consistent with that
observed in previously reported studies involving patients with advanced
urothelial cancer. The treatment-related adverse events observed in this
trial (any grade occurring in 10 percent or more) were pruritus (19.5%
with KEYTRUDA; 2.7% with chemotherapy), fatigue (13.9% with KEYTRUDA;
27.8% with chemotherapy), nausea (10.9% with KEYTRUDA; 24.3% with
chemotherapy), diarrhea (9.0% with KEYTRUDA; 12.9% with chemotherapy),
decreased appetite (8.6% with KEYTRUDA; 16.1% with chemotherapy),
asthenia (5.6% with KEYTRUDA; 14.1% with chemotherapy), anemia (3.4%
with KEYTRUDA; 24.7% with chemotherapy), constipation (2.3% with
KEYTRUDA; 20.4% with chemotherapy), peripheral sensory neuropathy (0.8%
with KEYTRUDA; 11.0% with chemotherapy), peripheral neuropathy (0.4%
with KEYTRUDA; 10.6% with chemotherapy), neutrophil count decreased
(0.4% with KEYTRUDA (pembrolizumab); 14.1% with chemotherapy), alopecia
(37.6% with chemotherapy) and neutropenia (15.3% with chemotherapy).
Immune-mediated adverse events were thyroid abnormalities (9.4% with
KEYTRUDA (pembrolizumab); 1.6% with chemotherapy), pneumonitis (4.1%
with KEYTRUDA; 0.4% with chemotherapy), colitis (2.3% with KEYTRUDA;
0.4% with chemotherapy), infusion reactions (0.8% with KEYTRUDA; 3.9%
with chemotherapy), severe skin toxicity (0.8% with KEYTRUDA; 1.2% with
chemotherapy), nephritis (0.8% with KEYTRUDA), adrenal insufficiency
(0.4% with KEYTRUDA) and myositis (0.4% with chemotherapy). Fifteen
patients in the KEYTRUDA arm and 28 patients in the chemotherapy arm
discontinued treatment due to a treatment-related adverse event; there
were four treatment-related deaths in each arm.

About Bladder Cancer

Bladder cancer begins when cells in the urinary bladder start to grow
uncontrollably. As more cancer cells develop, they can form a tumor and
spread to other areas of the body. Urothelial carcinoma, the most common
type of bladder cancer, starts in the urothelial cells that line the
inside of the bladder. In 2012, approximately 430,000 people worldwide
were diagnosed with bladder cancer and 165,000 died from the disease.
The incidence of bladder cancer is elevated in North America, Europe,
North Africa, the Middle East, Australia and New Zealand.

About KEYTRUDA

^®

(pembrolizumab)

KEYTRUDA is a humanized monoclonal antibody that works by increasing the
ability of the body’s immune system to help detect and fight tumor
cells. KEYTRUDA blocks the interaction between PD-1 and its ligands,
PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both
tumor cells and healthy cells.

KEYTRUDA is administered as an intravenous infusion over 30 minutes
every three weeks for the approved indications. KEYTRUDA for injection
is supplied in a 100 mg single use vial.

KEYTRUDA Indications and Dosing

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or
metastatic melanoma at a dose of 2 mg/kg every three weeks until disease
progression or unacceptable toxicity.

Lung Cancer

KEYTRUDA is indicated for the first-line treatment of patients with
metastatic non-small cell lung cancer (NSCLC) whose tumors have high
PD-L1 expression [tumor proportion score (TPS) ≥50%] as determined by an
FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA (pembrolizumab) is also indicated for the treatment of patients
with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined
by an FDA-approved test, with disease progression on or after
platinum-containing chemotherapy. Patients with EGFR or ALK genomic
tumor aberrations should have disease progression on FDA-approved
therapy for these aberrations prior to receiving KEYTRUDA.

In metastatic NSCLC, KEYTRUDA is administered at a fixed dose of 200 mg
every three weeks until disease progression, unacceptable toxicity, or
up to 24 months in patients without disease progression.

Head and Neck Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or
metastatic head and neck squamous cell carcinoma (HNSCC) with disease
progression on or after platinum-containing chemotherapy. This
indication is approved under accelerated approval based on tumor
response rate and durability of response. Continued approval for this
indication may be contingent upon verification and description of
clinical benefit in the confirmatory trials. In HNSCC, KEYTRUDA is
administered at a fixed dose of 200 mg every three weeks until disease
progression, unacceptable toxicity, or up to 24 months in patients
without disease progression.

Selected Important Safety Information for KEYTRUDA

^®
 (pembrolizumab)

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases.
Pneumonitis occurred in 94 (3.4%) of 2799 patients receiving KEYTRUDA,
including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%)
pneumonitis, and occurred more frequently in patients with a history of
prior thoracic radiation (6.9%) compared to those without (2.9%).
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 or
recurrent Grade 2 pneumonitis.

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 48
(1.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.4%), 3
(1.1%), and 4 (<0.1%) colitis. 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.

KEYTRUDA (pembrolizumab) can cause immune-mediated hepatitis. Hepatitis
occurred in 19 (0.7%) of 2799 patients receiving KEYTRUDA, including
Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%) hepatitis. 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.

KEYTRUDA can cause hypophysitis. Hypophysitis occurred in 17 (0.6%) of
2799 patients receiving KEYTRUDA, including Grade 2 (0.2%), 3 (0.3%),
and 4 (<0.1%) hypophysitis. Monitor patients for signs and symptoms of
hypophysitis (including hypopituitarism and adrenal insufficiency).
Administer corticosteroids and hormone replacement as clinically
indicated. Withhold KEYTRUDA for Grade 2; withhold or discontinue for
Grade 3 or 4 hypophysitis.

KEYTRUDA can cause thyroid disorders, including hyperthyroidism,
hypothyroidism, and thyroiditis. Hyperthyroidism occurred in 96 (3.4%)
of 2799 patients receiving KEYTRUDA, including Grade 2 (0.8%) and 3
(0.1%) hyperthyroidism. Hypothyroidism occurred in 237 (8.5%) of 2799
patients receiving KEYTRUDA, including Grade 2 (6.2%) and 3 (0.1%)
hypothyroidism. The incidence of new or worsening hypothyroidism was
higher in patients with HNSCC occurring in 28 (15%) of 192 patients with
HNSCC, including Grade 3 (0.5%) hypothyroidism. Thyroiditis occurred in
16 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.3%)
thyroiditis. 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 replacement hormones for hypothyroidism
and manage hyperthyroidism with thionamides and beta-blockers as
appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4
hyperthyroidism.

KEYTRUDA can cause type 1 diabetes mellitus, including diabetic
ketoacidosis, which have been reported in 6 (0.2%) of 2799 patients.
Monitor patients for hyperglycemia or other signs and symptoms of
diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA
and administer antihyperglycemics in patients with severe hyperglycemia.

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 9
(0.3%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3
(0.1%), and 4 (<0.1%) nephritis. 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.

KEYTRUDA can cause other clinically important immune-mediated adverse
reactions. 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 to Grade 1 or less,
initiate corticosteroid taper and continue to taper over at least 1
month. Based on limited data from clinical studies in patients whose
immune-related adverse reactions could not be controlled with
corticosteroid use, administration of other systemic immunosuppressants
can be considered. Resume KEYTRUDA when the adverse reaction remains at
Grade 1 or less following corticosteroid taper. Permanently discontinue
KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs
and for any life-threatening immune-mediated adverse reaction.

The following clinically significant immune-mediated adverse reactions
occurred in less than 1% (unless otherwise indicated) of 2799 patients:
arthritis (1.5%), exfoliative dermatitis, bullous pemphigoid, rash
(1.4%), uveitis, myositis, Guillain-Barré syndrome, myasthenia gravis,
vasculitis, pancreatitis, hemolytic anemia, and partial seizures arising
in a patient with inflammatory foci in brain parenchyma.

KEYTRUDA can cause severe or life-threatening infusion-related
reactions, which have been reported in 6 (0.2%) of 2799 patients.
Monitor patients for signs and symptoms of infusion-related reactions,
including rigors, chills, wheezing, pruritus, flushing, rash,
hypotension, hypoxemia, and fever. For Grade 3 or 4 reactions, stop
infusion and permanently discontinue KEYTRUDA.

Based on its mechanism of action, KEYTRUDA can 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.

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9%
of 555 patients with advanced melanoma; adverse reactions leading to
discontinuation in more than one patient were colitis (1.4%), autoimmune
hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and
cardiac failure (0.4%). Adverse reactions leading to interruption of
KEYTRUDA occurred in 21% of patients; the most common (≥1%) was diarrhea
(2.5%). The most common adverse reactions with KEYTRUDA vs ipilimumab
were fatigue (28% vs 28%), diarrhea (26% with KEYTRUDA), rash (24% vs
23%), and nausea (21% with KEYTRUDA). Corresponding incidence rates are
listed for ipilimumab only for those adverse reactions that occurred at
the same or lower rate than with KEYTRUDA (pembrolizumab).

In KEYNOTE-002, KEYTRUDA was discontinued due to adverse reactions in
12% of 357 patients with advanced melanoma; the most common (≥1%) were
general physical health deterioration (1%), asthenia (1%), dyspnea (1%),
pneumonitis (1%), and generalized edema (1%). Adverse reactions leading
to interruption of KEYTRUDA (pembrolizumab) occurred in 14% of patients;
the most common (≥1%) were dyspnea (1%), diarrhea (1%), and
maculopapular rash (1%). The most common adverse reactions with KEYTRUDA
vs chemotherapy were fatigue (43% with KEYTRUDA), pruritus (28% vs 8%),
rash (24% vs 8%), constipation (22% vs 20%), nausea (22% with KEYTRUDA),
diarrhea (20% vs 20%), and decreased appetite (20% with KEYTRUDA).
Corresponding incidence rates are listed for chemotherapy only for those
adverse reactions that occurred at the same or lower rate than with
KEYTRUDA.

KEYTRUDA was discontinued due to adverse reactions in 8% of 682 patients
with metastatic NSCLC. The most common adverse event resulting in
permanent discontinuation of KEYTRUDA was pneumonitis (1.8%). Adverse
reactions leading to interruption of KEYTRUDA occurred in 23% of
patients; the most common (≥1%) were diarrhea (1%), fatigue (1.3%),
pneumonia (1%), liver enzyme elevation (1.2%), decreased appetite
(1.3%), and pneumonitis (1%). The most common adverse reactions
(occurring in at least 20% of patients and at a higher incidence than
with docetaxel) were decreased appetite (25% vs 23%), dyspnea (23% vs
20%), and nausea (20% vs 18%).

KEYTRUDA was discontinued due to adverse reactions in 17% of 192
patients with HNSCC. Serious adverse reactions occurred in 45% of
patients. The most frequent serious adverse reactions reported in at
least 2% of patients were pneumonia, dyspnea, confusional state,
vomiting, pleural effusion, and respiratory failure. The most common
adverse reactions (reported in at least 20% of patients) were fatigue,
decreased appetite, and dyspnea. Adverse reactions occurring in patients
with HNSCC were generally similar to those occurring in patients with
melanoma or NSCLC, with the exception of increased incidences of facial
edema (10% all Grades; 2.1% Grades 3 or 4) and new or worsening
hypothyroidism.

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 and for 4 months after the final dose.

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, 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.

As part of our focus on cancer, Merck is committed to exploring the
potential of immuno-oncology with one of the fastest-growing development
programs in the industry. We are currently executing an expansive
research program that includes more than 360 clinical trials evaluating
our anti-PD-1 therapy across more than 30 tumor types. We also continue
to strengthen our immuno-oncology portfolio through strategic
acquisitions and are prioritizing the development of several promising
immunotherapeutic candidates with the potential to improve the treatment
of advanced cancers.

For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

About Merck

For 125 years, Merck has been a global health care 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
health care 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 LinkedIn.

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 health care legislation in the
United States and internationally; global trends toward health care 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 2015 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

Patient Information/Medication Guide for KEYTRUDA at 

http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf

Merck
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