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October 18, 2017 5:45 am ET

Data Showed Median Overall Survival of 30.0 Months for KEYTRUDA Group Compared to 14.2 Months for Chemotherapy Group

Findings from KEYNOTE-024 to Be Presented at World Conference on Lung Cancer

Merck (NYSE: MRK), known as MSD outside the United States and Canada,
today announced the presentation of updated overall survival (OS)
findings, a secondary endpoint, from the phase 3 KEYNOTE-024 trial
evaluating KEYTRUDA^® (pembrolizumab), the company’s anti-PD-1
therapy, as a first-line monotherapy in patients with non-small cell
lung cancer (NSCLC) whose tumors express high levels of PD-L1 (tumor
proportion score [TPS] of 50 percent or more). The study included
patients with squamous and nonsquamous NSCLC with no EGFR or ALK genomic
tumor aberrations. Findings – which are based on more than two years of
follow-up – will be presented in an oral presentation at the 18th World
Conference on Lung Cancer (WCLC) hosted by the International Association
for the Study of Lung Cancer in Yokohama, Japan (Abstract OA 17.06).

With an additional six months of available data, results continue to
show a reduction in the risk of death by 37 percent for KEYTRUDA
compared to chemotherapy based on more than two years of median
follow-up (HR, 0.63 [95% CI, 0.47–0.86]; nominal p=0.002). Additionally,
KEYTRUDA increased OS by more than one year, more than double the OS for
chemotherapy (30.0 months [95% CI, 18.3–not reached]; 14.2 months [95%
CI, 9.8–19.0], respectively).

“As we continue to see updated findings from this study of patients with
non-small cell lung cancer in the first-line setting, practioners are
gaining valuable insights into the longer-term clinical benefit of
KEYTRUDA,” said Prof. Martin Reck, head of the department of thoracic
oncology, LungenClinic Grosshansdorf, Germany. “The significant overall
survival findings observed in KEYNOTE-024, which includes patients who
have a poor prognosis, reinforce the use of KEYTRUDA in appropriate
patients in the first-line treatment of this disease.”

Merck has an extensive research program in NSCLC and is currently
advancing multiple registration-enabling studies with KEYTRUDA
(pembrolizumab) as monotherapy and in combination with other treatments.

“The focus of our clinical program has always been to improve survival
for people with cancer,” said Dr. Roger Dansey, senior vice president
and therapeutic area head, oncology late-stage development, Merck
Research Laboratories. “With these findings from KEYNOTE-024, we
continue to demonstrate the potential for KEYTRUDA to have a positive
impact on survival outcomes in non-small cell lung cancer.”

Data from KEYNOTE-024 Study (Abstract OA 17.06)

KEYNOTE-024
studied 305 patients with metastatic NSCLC who were assigned either
KEYTRUDA as monotherapy (n=154) or standard of care platinum-based
chemotherapy (n=151). Enrollment criteria included: having no prior
systemic chemotherapy treatment for their advanced disease, tumors
without an EGFR sensitizing mutation or ALK translocation, and tumors
expressing high levels of PD-L1 (TPS of 50 percent or more) as
determined by a central laboratory FDA-approved test. The primary
endpoint was progression-free survival (PFS) and the key secondary
endpoint was OS. Other secondary endpoints include overall response rate
(ORR) and safety. Exploratory endpoints include duration of response.

Data presented at WCLC are based on a median follow-up of 25.2 months in
305 patients and include findings from 82 patients who crossed over from
the chemotherapy group to receive KEYTRUDA, per study protocol, and 12
patients who received anti-PD-1 therapy outside of study crossover,
totaling a 62.3 percent effective crossover rate.

With an additional six months of follow-up, an analysis of OS
demonstrated that the median OS for the KEYTRUDA group was 30.0 months
(95% CI, 18.3–not reached) and the median OS for the chemotherapy group
was 14.2 months (95% CI, 9.8–19.0). Consistent with previously reported
findings, KEYTRUDA was also associated with a 37 percent reduction in
the risk of death compared to chemotherapy (HR, 0.63 [95% CI,
0.47-0.86]; nominal p=0.002). The 24-month OS rate was 51.5 percent in
the KEYTRUDA group compared to 34.5 percent in the chemotherapy group;
at 12 months, the OS rate was 70.3 percent in the KEYTRUDA
(pembrolizumab) group compared to 54.8 percent in the chemotherapy group.

ORR was 45.5 percent (95% CI, 37.4-53.7) in the KEYTRUDA group compared
to 29.8 percent (95% CI, 22.6-37.8) in the chemotherapy group. Median
duration of response was not reached in the KEYTRUDA group (range: 1.8+
to 20.6+ months) compared to 7.1 months (range: 2.1+ to 18.1+) in the
chemotherapy group.

The safety of KEYTRUDA was consistent with what has been seen in
previous trials among patients with metastatic NSCLC. In the KEYTRUDA
group, 31.2 percent of patients experienced Grade 3-5 treatment-related
adverse events (TRAEs). The most common TRAEs for KEYTRUDA were
diarrhea, fatigue, pyrexia, pruritus, nausea, decreased appetite and
rash. The most common immune-mediated adverse events in patients
receiving KEYTRUDA were hypothyroidism, pneumonitis, hyperthyroidism,
severe skin toxicity and infusion reactions. There was one
treatment-related death in the KEYTRUDA group.

About Lung Cancer

Lung cancer, which forms in the tissues of
the lungs, usually within cells lining the air passages, is the leading
cause of cancer death worldwide. Each year, more people die of lung
cancer than colon, breast and prostate cancers combined. The two main
types of lung cancer are non-small cell and small cell. NSCLC is the
most common type of lung cancer, accounting for about 85 percent of all
cases. The five-year survival rate for patients suffering from highly
advanced, metastatic (Stage IV) lung cancers is estimated to be two
percent.

About KEYTRUDA 

^® 

(pembrolizumab)
Injection 100 mg

KEYTRUDA is an anti-PD-1 therapy that
works by increasing the ability of the body’s immune system to help
detect and fight tumor cells. KEYTRUDA is a humanized monoclonal
antibody that 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.

Merck has the industry’s largest immuno-oncology clinical research
program, which currently involves more than 600 trials studying KEYTRUDA
across a wide variety of cancers and treatment settings. The KEYTRUDA
clinical program seeks to understand the role of KEYTRUDA across cancers
and the factors that may predict a patient’s likelihood of benefitting
from treatment with KEYTRUDA, including exploring several different
biomarkers.

KEYTRUDA (pembrolizumab) Indications and Dosing

Melanoma

KEYTRUDA is indicated for the treatment of patients
with unresectable or metastatic melanoma at a fixed dose of 200 mg every
three weeks until disease progression or unacceptable toxicity.

Lung Cancer

KEYTRUDA, as a single agent, 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, as a single agent, 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.

KEYTRUDA, in combination with pemetrexed and carboplatin, is indicated
for the first-line treatment of patients with metastatic nonsquamous
NSCLC. This indication is approved under accelerated approval based on
tumor response rate and progression-free survival. Continued approval
for this indication may be contingent upon verification and description
of clinical benefit in the confirmatory trials.

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.

When administering KEYTRUDA in combination with chemotherapy, KEYTRUDA
should be administered prior to chemotherapy when given on the same day.
See also the Prescribing Information for pemetrexed and carboplatin.

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 (pembrolizumab) 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.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the
treatment of adult and pediatric patients with refractory classical
Hodgkin lymphoma (cHL), or who have relapsed after three or more prior
lines of therapy. 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 adults
with cHL, KEYTRUDA is administered at a fixed dose of 200 mg every three
weeks until disease progression or unacceptable toxicity, or up to 24
months in patients without disease progression. In pediatric patients
with cHL, KEYTRUDA is administered at a dose of 2 mg/kg (up to a maximum
of 200 mg) every three weeks until disease progression or unacceptable
toxicity, or up to 24 months in patients without disease progression.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment
of patients with locally advanced or metastatic urothelial carcinoma who
are not eligible for cisplatin-containing chemotherapy. This indication
is approved under accelerated approval based on tumor response rate and
duration of response. Continued approval for this indication may be
contingent upon verification and description of clinical benefit in the
confirmatory trials.

KEYTRUDA is also indicated for the treatment of patients with locally
advanced or metastatic urothelial carcinoma who have disease progression
during or following platinum-containing chemotherapy or within 12 months
of neoadjuvant or adjuvant treatment with platinum-containing
chemotherapy.

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

Microsatellite Instability-High (MSI-H) Cancer

KEYTRUDA is
indicated for the treatment of adult and pediatric patients with
unresectable or metastatic microsatellite instability-high (MSI-H) or
mismatch repair deficient (dMMR)

• solid tumors that have progressed following prior treatment and who
  have no satisfactory alternative treatment options, or
• colorectal cancer that has progressed following treatment with
  fluoropyrimidine, oxaliplatin, and irinotecan.

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. The safety and
effectiveness of KEYTRUDA (pembrolizumab) in pediatric patients with
MSI-H central nervous system cancers have not been established.

In adult patients with MSI-H cancer, 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. In
children with MSI-H cancer, KEYTRUDA is administered at a dose of 2
mg/kg (up to a maximum of 200 mg) every three weeks until disease
progression or unacceptable toxicity, or up to 24 months in patients
without disease progression.

Gastric Cancer

KEYTRUDA is indicated for the treatment of
patients with recurrent locally advanced or metastatic gastric or
gastroesophageal junction (GEJ) adenocarcinoma whose tumors express
PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an
FDA-approved test, with disease progression on or after two or more
prior lines of therapy including fluoropyrimidine- and
platinum-containing chemotherapy and if appropriate, HER2/neu-targeted
therapy. 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. The recommended dose of
KEYTRUDA is 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
(pembrolizumab) 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 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
(pembrolizumab) 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.

Immune-mediated rashes, including Stevens-Johnson syndrome (SJS), toxic
epidermal necrolysis (TEN) (some cases with fatal outcome), exfoliative
dermatitis, and bullous pemphigoid, can occur. Monitor patients for
suspected severe skin reactions and based on the severity of the adverse
reaction, withhold or permanently discontinue KEYTRUDA and administer
corticosteroids. For signs and symptoms of SJS or TEN, withhold KEYTRUDA
and refer the patient for specialized care for assessment and treatment.
If SJS or TEN is confirmed, permanently discontinue KEYTRUDA.

KEYTRUDA can cause other clinically important immune-mediated adverse
reactions. These immune-mediated reactions may occur in any organ
system. 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%), uveitis, myositis, Guillain-Barré syndrome, myasthenia
gravis, vasculitis, pancreatitis, hemolytic anemia, and partial seizures
arising in a patient with inflammatory foci in brain parenchyma. In
addition, myelitis and myocarditis were reported in other clinical
trials, including classical Hodgkin lymphoma, and post-marketing use.

Solid organ transplant rejection has been reported in postmarketing use
of KEYTRUDA. Treatment with KEYTRUDA may increase the risk of rejection
in solid organ transplant recipients. Consider the benefit of treatment
with KEYTRUDA (pembrolizumab) vs the risk of possible organ rejection in
these patients.

KEYTRUDA can cause severe or life-threatening infusion-related
reactions, including hypersensitivity and anaphylaxis, 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.

Immune-mediated complications, including fatal events, occurred in
patients who underwent allogeneic hematopoietic stem cell
transplantation (HSCT) after being treated with KEYTRUDA. Of 23 patients
with cHL who proceeded to allogeneic HSCT after treatment with KEYTRUDA
on any trial, 6 patients (26%) developed graft-versus-host disease
(GVHD), one of which was fatal, and 2 patients (9%) developed severe
hepatic veno-occlusive disease (VOD) after reduced-intensity
conditioning, one of which was fatal. Cases of fatal hyperacute GVHD
after allogeneic HSCT have also been reported in patients with lymphoma
who received a PD-1 receptor–blocking antibody before transplantation.
These complications may occur despite intervening therapy between PD-1
blockade and allogeneic HSCT. Follow patients closely for early evidence
of transplant-related complications such as hyperacute GVHD, severe
(Grade 3 to 4) acute GVHD, steroid-requiring febrile syndrome, hepatic
VOD, and other immune-mediated adverse reactions, and intervene promptly.

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.

In KEYNOTE-010, KEYTRUDA (pembrolizumab) monotherapy 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%).

In KEYNOTE-021G(1), when KEYTRUDA was administered in combination with
carboplatin and pemetrexed (carbo/pem) in advanced nonsquamous NSCLC,
KEYTRUDA was discontinued in 10% of 59 patients. The most common adverse
reaction resulting in discontinuation of KEYTRUDA (≥2%) was acute kidney
injury (3.4%). Adverse reactions leading to interruption of KEYTRUDA
occurred in 39% of patients; the most common (≥2%) were fatigue (8%),
neutrophil count decreased (8%), anemia (5%), dyspnea (3.4%), and
pneumonitis (3.4%).The most common adverse reactions (≥20%) with
KEYTRUDA compared to carbo/pem alone were fatigue (71% vs 50%), nausea
(68% vs 56%), constipation (51% vs 37%), rash (42% vs 21%), vomiting
(39% vs 27%), dyspnea (39% vs 21%), diarrhea (37% vs 23%), decreased
appetite (31% vs 23%), headache (31% vs 16%), cough (24% vs 18%),
dizziness (24% vs 16%), insomnia (24% vs 15%), pruritus (24% vs 4.8%),
peripheral edema (22% vs 18%), dysgeusia (20% vs 11%), alopecia (20% vs
3.2%), upper respiratory tract infection (20% vs 3.2%), and arthralgia
(15% vs 24%). This study was not designed to demonstrate a statistically
significant difference in adverse reaction rates for KEYTRUDA as
compared to carbo/pem alone for any specified adverse reaction.

In KEYNOTE-012, 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.

In KEYNOTE-087, KEYTRUDA was discontinued due to adverse reactions in 5%
of 210 patients with cHL, and treatment was interrupted due to adverse
reactions in 26% of patients. Fifteen percent (15%) of patients had an
adverse reaction requiring systemic corticosteroid therapy. Serious
adverse reactions occurred in 16% of patients. The most frequent serious
adverse reactions (≥1%) included pneumonia, pneumonitis, pyrexia,
dyspnea, GVHD, and herpes zoster. Two patients died from causes other
than disease progression; one from GVHD after subsequent allogeneic HSCT
and one from septic shock. The most common adverse reactions (occurring
in ≥20% of patients) were fatigue (26%), pyrexia (24%), cough (24%),
musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

In KEYNOTE-052, KEYTRUDA (pembrolizumab) was discontinued due to adverse
reactions in 11% of 370 patients with locally advanced or metastatic
urothelial carcinoma. The most common adverse reactions (in≥20% of
patients) were fatigue (38%), musculoskeletal pain (24%), decreased
appetite (22%), constipation (21%), rash (21%), and diarrhea (20%).
Eighteen patients (5%) died from causes other than disease progression.
Five patients (1.4%) who were treated with KEYTRUDA experienced sepsis
which led to death, and 3 patients (0.8%) experienced pneumonia which
led to death. Adverse reactions leading to interruption of KEYTRUDA
occurred in 22% of patients; the most common (≥1%) were liver enzyme
increase, diarrhea, urinary tract infection, acute kidney injury,
fatigue, joint pain, and pneumonia. Serious adverse reactions occurred
in 42% of patients, the most frequent (≥2%) of which were urinary tract
infection, hematuria, acute kidney injury, pneumonia, and urosepsis.

In KEYNOTE-045, KEYTRUDA was discontinued due to adverse reactions in 8%
of 266 patients with locally advanced or metastatic urothelial
carcinoma. The most common adverse reaction resulting in permanent
discontinuation of KEYTRUDA was pneumonitis (1.9%). Adverse reactions
leading to interruption of KEYTRUDA occurred in 20% of patients; the
most common (≥1%) were urinary tract infection (1.5%), diarrhea (1.5%),
and colitis (1.1%). The most common adverse reactions (20%) in patients
who received KEYTRUDA vs those who received chemotherapy were fatigue
(38% vs 56%), musculoskeletal pain (32% vs 27%), pruritus (23% vs 6%),
decreased appetite (21% vs 21%), nausea (21% vs 29%), and rash (20% vs
13%). Serious adverse reactions occurred in 39% of KEYTRUDA-treated
patients, the most frequent (≥2%) of which were urinary tract infection,
pneumonia, anemia, and pneumonitis.

There is limited experience in pediatric patients. Efficacy for
pediatric patients was extrapolated from the results in the adult cHL
population. In a study of 40 pediatric patients with advanced melanoma,
PD-L1–positive advanced, relapsed, or refractory solid tumors or
lymphoma, patients were treated with KEYTRUDA for a median of 43 days
(range 1-414 days), with 24 patients (60%) receiving treatment for 42
days or more. The safety profile in pediatric patients was similar to
that seen in adults treated with KEYTRUDA. Toxicities that occurred at a
higher rate (≥15% difference) in these patients when compared to adults
under 65 years of age were fatigue (45%), vomiting (38%), abdominal pain
(28%), hypertransaminasemia (28%), and hyponatremia (18%).

It is not known whether KEYTRUDA (pembrolizumab) 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.

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 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 more than a century, Merck, a leading global
biopharmaceutical company known as MSD outside of the United States and
Canada, has been inventing for life, bringing forward medicines and
vaccines for many of the world’s most challenging diseases. 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
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including cancer, cardio-metabolic diseases, emerging animal diseases,
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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 2016 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 & Co., Inc.
Media:
Pamela Eisele, 267-305-3558
or
Teresa Mueller, 908-740-1884
or
Investors:
Teri Loxam, 908-740-1986
or
Amy Klug, 908-740-1898