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October 18, 2018 5:57 am ET

KEYTRUDA is First Anti-PD-1 Therapy in Combination to Improve Both OS and PFS in Advanced or Metastatic RCC, the Most Common Type of Kidney Cancer

Pivotal Phase 3 KEYNOTE-426 Trial Met Both Primary Endpoints; Data to be Filed with Global Regulatory Authorities

KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE: MRK), known as MSD outside the United States and Canada,
announced today that the pivotal Phase 3 KEYNOTE-426 trial investigating
KEYTRUDA^® (pembrolizumab), Merck’s anti-PD-1 therapy, in
combination with Inlyta^® (axitinib), Pfizer’s tyrosine kinase
inhibitor, met both primary endpoints of overall survival (OS) and
progression-free survival (PFS) in the first-line treatment of advanced
or metastatic renal cell carcinoma (RCC), the most common type of kidney
cancer. Based on the first interim analysis by the independent Data
Monitoring Committee (DMC), the KEYTRUDA plus Inlyta combination
resulted in statistically significant and clinically meaningful
improvements in OS and PFS, compared to sunitinib monotherapy. The study
also met the key secondary endpoint of objective response rate (ORR),
with significant improvements for the KEYTRUDA and Inlyta combination
compared with sunitinib monotherapy. Results for OS, PFS and ORR were
consistent regardless of PD-L1 expression and across all risk groups.
The safety profile of KEYTRUDA and Inlyta in this trial was generally
consistent with that observed in previously reported studies for each
therapy. These results will be presented at an upcoming medical meeting
and submitted to regulatory authorities worldwide.

“KEYTRUDA, in combination with the tyrosine kinase inhibitor Inlyta,
resulted in significant and clinically meaningful improvements in
overall survival, progression-free survival and objective response in
this Phase 3 study. This marks the first time that combination treatment
with an anti-PD-1 therapy has achieved the dual primary endpoints of
overall survival and progression-free survival as first-line therapy in
advanced renal cell carcinoma,” said Dr. Roger M. Perlmutter, president,
Merck Research Laboratories. “Fewer than 10 percent of those diagnosed
with advanced renal cell carcinoma survive for five years, and hence
there is significant need for improved therapies for this disease. We
are very grateful to the investigators and patients for their
involvement in this important study, the results of which will be filed
with global regulatory authorities in the near future.”

About KEYNOTE-426

KEYNOTE-426 is a randomized, double-arm,
Phase 3 trial (ClinicalTrials.gov, NCT02853331) evaluating the safety
and efficacy of KEYTRUDA in combination with Inlyta as first-line
treatment for advanced or metastatic RCC compared to sunitinib. The dual
primary endpoints of the study were OS and PFS, and the key secondary
endpoint was ORR. Additional secondary endpoints were disease control
rate (DCR), number of participants who experienced or discontinued the
study due to an adverse event (AE), duration of response (DOR), PFS at
12, 18 and 24 months and OS at 12, 18 and 24 months. In the trial, 861
patients were randomly assigned to receive KEYTRUDA 200 mg intravenously
every three weeks plus Inlyta 5 mg orally twice daily for up to 24
months, or sunitinib 50 mg orally once daily for four weeks followed by
no treatment for two weeks, continuously.

About Renal Cell Carcinoma (RCC)

Renal cell carcinoma (RCC)
is by far the most common type of kidney cancer; about 9 out of 10
kidney cancers are renal cell carcinomas. RCC is about twice as common
in men as in women. Modifiable risk factors include smoking, obesity,
workplace exposure to certain substances and high blood pressure. There
are expected to be approximately 403,262 cases of kidney cancer
diagnosed worldwide in 2018 and about 175,098 people will die from the
disease. In the U.S. alone, there will be an estimated 63,340 new cases
of kidney cancer diagnosed in 2018 and about 14,970 people will die from
the disease

About KEYTRUDA

^®

(pembrolizumab) Injection,
100mg

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. There are currently more than 850 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, in combination with pemetrexed and platinum chemotherapy, is
indicated for the first-line treatment of patients with metastatic
nonsquamous NSCLC, with no EGFR or ALK genomic tumor aberrations.

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.

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 or
cisplatin, as appropriate.

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.

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.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients
with refractory primary mediastinal large B-cell lymphoma (PMBCL), or
who have relapsed after 2 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 confirmatory trials. KEYTRUDA is not recommended for
the treatment of patients with PMBCL who require urgent cytoreductive
therapy.

In adults with PMBCL, 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 pediatric
patients with PMBCL, 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 (mUC) who are not eligible
for cisplatin-containing chemotherapy and whose tumors express PD-L1
[Combined Positive Score (CPS) ≥10] as determined by an FDA-approved
test, or in patients who are not eligible for any platinum-containing
chemotherapy regardless of PD-L1 status. 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 (mUC) 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 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 a fixed dose of
200 mg every three weeks until disease progression, unacceptable
toxicity, or up to 24 months in patients without disease progression.

Cervical Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or
metastatic cervical cancer with disease progression on or after
chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an
FDA-approved test. 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 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

Immune-Mediated Pneumonitis

KEYTRUDA can cause
immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred
in 3.4% (94/2799) of patients receiving KEYTRUDA, including Grade 1
(0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%), 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 for
Grade 3 or 4 or recurrent Grade 2 pneumonitis.

Immune-Mediated Colitis

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

Immune-Mediated Hepatitis

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

Immune-Mediated Endocrinopathies

KEYTRUDA can cause
hypophysitis, thyroid disorders, and type 1 diabetes mellitus.
Hypophysitis occurred in 0.6% (17/2799) of patients, including Grade 2
(0.2%), 3 (0.3%), and 4 (<0.1%). Hypothyroidism occurred in 8.5%
(237/2799) of patients, including Grade 2 (6.2%) and 3 (0.1%). The
incidence of new or worsening hypothyroidism was higher in patients with
HNSCC occurring in 15% (28/192) of patients. Hyperthyroidism occurred in
3.4% (96/2799) of patients, including Grade 2 (0.8%) and 3 (0.1%), and
thyroiditis occurred in 0.6% (16/2799) of patients, including Grade 2
(0.3%). Type 1 diabetes mellitus, including diabetic ketoacidosis,
occurred in 0.2% (6/2799) of patients.

Monitor patients for signs and symptoms of hypophysitis (including
hypopituitarism and adrenal insufficiency), thyroid function (prior to
and periodically during treatment), and hyperglycemia. For hypophysitis,
administer corticosteroids and hormone replacement as clinically
indicated. Withhold KEYTRUDA for Grade 2 and withhold or discontinue for
Grade 3 or 4 hypophysitis. Administer hormone replacement for
hypothyroidism and manage hyperthyroidism with thionamides and
beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade
3 or 4 hyperthyroidism. Administer insulin for type 1 diabetes, and
withhold KEYTRUDA and administer anti-hyperglycemics in patients with
severe hyperglycemia.

Immune-Mediated Nephritis and Renal Dysfunction

KEYTRUDA can
cause immune-mediated nephritis. Nephritis occurred in 0.3% (9/2799) of
patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4
(<0.1%) nephritis. Nephritis occurred in 1.7% (7/405) of patients
receiving KEYTRUDA in combination with pemetrexed and platinum
chemotherapy. Monitor patients for changes in renal function. Administer
corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for
Grade 2; permanently discontinue for Grade 3 or 4 nephritis.

Immune-Mediated Skin Reactions

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 or 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.

Other Immune-Mediated Adverse Reactions

Immune-mediated
adverse reactions, which may be severe or fatal, can occur in any organ
system or tissue in patients receiving KEYTRUDA and may also occur after
discontinuation of treatment. 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, sarcoidosis, and
encephalitis. In addition, myelitis and myocarditis were reported in
other clinical trials and postmarketing use.

Treatment with KEYTRUDA may increase the risk of rejection in solid
organ transplant recipients. Consider the benefit of treatment vs the
risk of possible organ rejection in these patients.

Infusion-Related Reactions

KEYTRUDA can cause severe or
life-threatening infusion-related reactions, including hypersensitivity
and anaphylaxis, which have been reported in 0.2% (6/2799) of patients.
Monitor patients for signs and symptoms of infusion-related reactions.
For Grade 3 or 4 reactions, stop infusion and permanently discontinue
KEYTRUDA.

Complications of Allogenic Hematopoietic Stem Cell Transplantation
(HSCT)

Immune-mediated complications, including fatal events,
occurred in patients who underwent allogeneic HSCT after treatment with
KEYTRUDA. Of 23 patients with cHL who proceeded to allogeneic HSCT after
KEYTRUDA, 6 developed graft-versus-host disease (GVHD) (one fatal case)
and 2 developed severe hepatic veno-occlusive disease (VOD) after
reduced-intensity conditioning (one fatal case). 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. Follow patients closely for early evidence of
transplant-related complications such as hyperacute graft-versus-host
disease (GVHD), Grade 3 to 4 acute GVHD, steroid-requiring febrile
syndrome, hepatic veno-occlusive disease (VOD), and other
immune-mediated adverse reactions.

In patients with a history of allogeneic HSCT, acute GVHD (including
fatal GVHD), has been reported after treatment with KEYTRUDA. Patients
who experienced GVHD after their transplant procedure may be at
increased risk for GVHD after KEYTRUDA. Consider the benefit of KEYTRUDA
vs the risk of GVHD in these patients.

Increased Mortality in Patients with Multiple Myeloma

In
clinical trials in patients with multiple myeloma, the addition of
KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in
increased mortality. Treatment of these patients with a PD-1 or PD-L1
blocking antibody in this combination is not recommended outside of
controlled clinical trials.

Embryofetal Toxicity

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.

Adverse Reactions

In KEYNOTE-006, KEYTRUDA was discontinued
due to adverse reactions in 9% of 555 patients with advanced melanoma;
adverse reactions leading to permanent 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%). The
most common adverse reactions (≥20%) with KEYTRUDA were fatigue (28%),
diarrhea (26%), rash (24%), and nausea (21%).

In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and
platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was
discontinued due to adverse reactions in 20% of 405 patients. The most
common adverse reactions resulting in permanent discontinuation of
KEYTRUDA were pneumonitis (3%) and acute kidney injury (2%). The most
common adverse reactions (≥20%) with KEYTRUDA were nausea (56%), fatigue
(56%), constipation (35%), diarrhea (31%), decreased appetite (28%),
rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia
(20%).

In KEYNOTE-010, KEYTRUDA 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%). The most common adverse reactions (≥20%) were
decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%).

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 (≥20%) 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 and new or worsening
hypothyroidism.

In KEYNOTE-087, KEYTRUDA was discontinued due to adverse reactions in 5%
of 210 patients with cHL. Serious adverse reactions occurred in 16% of
patients; those ≥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 (≥20%) were
fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%),
diarrhea (20%), and rash (20%).

In KEYNOTE-170, KEYTRUDA was discontinued due to adverse reactions in 8%
of 53 patients with PMBCL. Serious adverse reactions occurred in 26% of
patients and included arrhythmia (4%), cardiac tamponade (2%),
myocardial infarction (2%), pericardial effusion (2%), and pericarditis
(2%). Six (11%) patients died within 30 days of start of treatment. The
most common adverse reactions (≥20%) were musculoskeletal pain (30%),
upper respiratory tract infection and pyrexia (28% each), cough (26%),
fatigue (23%), and dyspnea (21%).

In KEYNOTE-052, KEYTRUDA was discontinued due to adverse reactions in
11% of 370 patients with locally advanced or metastatic urothelial
carcinoma. Serious adverse reactions occurred in 42% of patients; those
≥2% were urinary tract infection, hematuria, acute kidney injury,
pneumonia, and urosepsis. The most common adverse reactions (≥20%) were
fatigue (38%), musculoskeletal pain (24%), decreased appetite (22%),
constipation (21%), rash (21%), and diarrhea (20%).

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%). Serious adverse
reactions occurred in 39% of KEYTRUDA-treated patients; those ≥2% were
urinary tract infection, pneumonia, anemia, and pneumonitis. The most
common adverse reactions (≥20%) in patients who received KEYTRUDA were
fatigue (38%), musculoskeletal pain (32%), pruritus (23%), decreased
appetite (21%), nausea (21%), and rash (20%).

In KEYNOTE-158, KEYTRUDA was discontinued due to adverse reactions in 8%
of 98 patients with recurrent or metastatic cervical cancer. Serious
adverse reactions occurred in 39% of patients receiving KEYTRUDA; the
most frequent included anemia (7%), fistula, hemorrhage, and infections
[except urinary tract infections] (4.1% each). The most common adverse
reactions (≥20%) were fatigue (43%), musculoskeletal pain (27%),
diarrhea (23%), pain and abdominal pain (22% each), and decreased
appetite (21%).

Lactation

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.

Pediatric Use

There is limited experience in pediatric
patients. In a study in 40 pediatric patients with advanced melanoma,
lymphoma, or PD-L1–positive advanced, relapsed, or refractory solid
tumors, the safety profile 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%).

Merck’s Focus on Cancer

Our goal is to translate
breakthrough science into innovative oncology medicines to help people
with cancer worldwide. At Merck, the potential to bring new hope to
people with cancer drives our purpose and supporting accessibility to
our cancer medicines is our commitment. As part of our focus on cancer,
Merck is committed to exploring the potential of immuno-oncology with
one of the largest development programs in the industry across more than
30 tumor types. We also continue to strengthen our portfolio through
strategic acquisitions and are prioritizing the development of several
promising oncology 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
commitment to increasing access to health care through far-reaching
policies, programs and partnerships. Today, Merck continues to be at the
forefront of research to advance the prevention and treatment of
diseases that threaten people and communities around the world –
including cancer, cardio-metabolic diseases, emerging animal diseases,
Alzheimer’s disease and infectious diseases including HIV and Ebola. For
more information, visit www.merck.com and connect
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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 2017 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 at 

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

 and

Medication Guide for KEYTRUDA at 

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

.

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