Updated Data for Merck’s KEYTRUDA® (pembrolizumab) in Patients with Advanced Gastric Cancer Across Treatment Settings to Be Presented at ESMO 2017 Congress

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September 8, 2017 7:00 am ET

KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE: MRK), known as MSD outside the United States and Canada,
today announced the presentation of data from all three cohorts of the
registrational, phase 2 KEYNOTE-059 trial investigating the use of
KEYTRUDA® (pembrolizumab), the company’s anti-PD-1 therapy,
in patients with advanced gastric or gastroesophageal junction (GEJ)
adenocarcinoma, including new data in treatment-naïve patients. Overall,
results showed antitumor activity and durability of response with
KEYTRUDA across multiple lines of therapy, with higher response rates
observed in PD-L1-positive (CPS ≥1) patients:

  • In heavily pre-treated patients, KEYTRUDA monotherapy (Cohort 1)
    showed an overall response rate (ORR) of 12 percent (95% CI, 8-17) in
    all patients and 16 percent (95% CI, 11-23) in patients with PD-L1
    positive tumors.
  • In treatment-naïve patients, KEYTRUDA in combination with chemotherapy
    (Cohort 2) showed an ORR of 60 percent (95% CI, 39-79) in all patients
    and 69 percent (95% CI, 41-89) in patients with PD-L1 positive tumors.
  • In treatment-naïve patients with PD-L1 positive tumors, KEYTRUDA
    monotherapy (Cohort 3) showed an ORR of 26 percent (95% CI, 12-45).

Results are being presented at the European Society for Medical Oncology
(ESMO) 2017 Congress in Madrid, Spain, in an oral presentation on
Friday, Sept. 8 from 3:03-3:15 p.m. CEST (Location: Barcelona
Auditorium) (Abstract #LBA28_PR).

“Outcomes can vary significantly among patients with gastric or GEJ
cancer – across stages of disease and based on a variety of biological
and molecular makeups of tumors,” said Charles S. Fuchs, M.D., MPH, lead
investigator and director of Yale Cancer Center. “KEYNOTE-059 was
designed to provide important insight across various treatment settings,
simultaneously, and these results show encouraging activity with
pembrolizumab in both previously treated and treatment-naïve patients,
particularly in those with high levels of PD-L1 expression.”

“These findings across lines of therapy in gastric and GEJ cancers
continue to support the potential for KEYTRUDA, and PD-L1 as a
biomarker, in patients with this advanced stage disease,” said Dr. Roger
Dansey, senior vice president and therapeutic area head, oncology
late-stage development, Merck Research Laboratories. “We are encouraged
by the responses observed in heavily pre-treated patients and look
forward to continued analysis of data in treatment-naïve patients.”

Merck’s broad clinical program encompasses multiple gastrointestinal
disorders – such as gastroesophageal cancer and microsatellite
instability-high (MSI-H) colorectal cancer – and includes four
gastric/GEJ cancer registration-enabling studies and numerous other
gastrointestinal cancer studies currently underway.

Data from KEYNOTE-059 Study Cohorts (Abstract #LBA28_PR)

Results presented from KEYNOTE-059 were based on an analysis of
efficacy, safety and PD-L1 expression from 315 patients across the
study’s three cohorts. Patients were considered PD-L1 positive if they
had a PD-L1 combined positive score of one or more (CPS ≥1). Findings
showed:

  • Cohort 1: KEYTRUDA (pembrolizumab) as
    monotherapy in patients whose disease progressed on or after two or
    more prior lines of therapy (n=259)
    . Forty-eight percent of
    these patients had received three or more lines of prior therapy. The
    efficacy analysis in all patients, with or without PD-L1 expression,
    showed an ORR of 12 percent (95% CI, 8-17), with complete responses
    (CR) in three percent (95% CI, 1-6) and partial responses (PR) in nine
    percent (95% CI, 6-13) of patients. In patients whose tumors expressed
    PD-L1 (n=148), the ORR was 16 percent (95% CI, 11-23), with CR in
    three percent (95% CI, 1-8) and PR in 13 percent (95% CI, 8-19) of
    patients. In PD-L1 negative patients (n=109), the ORR was six percent
    (95% CI, 3-13), with CR in three percent (95% CI, 1-8) and PR in four
    percent (95% CI, 1-9) of patients. Median duration of follow-up was
    5.6 months (range: 0.5-24.7). In all patients, 42 percent (n=95)
    experienced a reduction in target lesion size. Median duration of
    response was 14.2 months (range: 2.4-19.4+).

    In all
    patients, median progression-free survival (PFS) was two months (95%
    CI, 2.0-2.1), with a six-month PFS rate of 14.6 percent; the median
    overall survival (OS) was 5.5 months (95% CI, 4.2-6.5), with a
    six-month OS rate of 45.7 percent. In patients whose tumors expressed
    PD-L1, the median PFS was 2.1 months (95% CI, 2.0-2.1), with a
    six-month PFS rate of 18.2 percent; the median OS in these patients
    was 5.8 months (95% CI, 4.4-7.8), with a six-month OS rate of 48.4
    percent. In PD-L1 negative patients, the median PFS was two months
    (95% CI, 1.9-2.0), with a six-month PFS rate of 9.9 percent; the
    median OS was 4.6 months (95% CI, 3.2-6.5), with a six-month OS rate
    of 42.9 percent.

  • Cohort 2: KEYTRUDA (pembrolizumab) in
    combination with chemotherapy in treatment-naïve patients (n=25).
    The
    efficacy analysis in all patients showed an ORR of 60 percent (95% CI,
    39-79), with CR in four percent (95% CI, 0-20) and PR in 56 percent
    (95% CI, 35-76) of patients. In patients whose tumors expressed PD-L1
    (n=16), the ORR was 69 percent (95% CI, 41-89), with no complete
    responses (95% CI, 0-22) and PR in 69 percent (95% CI, 41-89) of
    patients. In PD-L1 negative patients (n=8), the ORR was 38 percent
    (95% CI, 9-76), with CR in 13 percent (95% CI, 0-53) and PR in 25
    percent (95% CI, 3-65) of patients. Median duration of follow-up was
    13.8 months (range: 1.8-24.1). Across all patients, 96 percent (n=24)
    experienced a reduction in target lesion size. Median duration of
    response was 4.6 months (range: 2.6-20.3+). In all patients, median
    PFS was 6.6 months (95% CI, 5.9-10.6), with a six-month PFS rate of
    68.0 percent; the median OS was 13.8 months (95% CI, 8.6-not reached),
    with a six-month OS rate of 76.0 percent.
  • Cohort 3: KEYTRUDA as monotherapy in
    treatment-naïve patients whose tumors expressed PD-L1 (n=31)
    .
    The efficacy analysis showed an ORR of 26 percent (95% CI, 12-45),
    with CR in seven percent (95% CI, 1-21) and PR in 19 percent (95% CI,
    8-38) of patients. Median duration of follow-up was 17.5 months
    (range: 1.7-20.7). Seventy-seven percent of patients (n=24)
    experienced a reduction in target lesion size. The median duration of
    response was 9.6 months (range: 2.1-17.8+). The median PFS was 3.3
    months (95% CI, 2.0-6.0), with a six-month PFS rate of 34.9 percent;
    the median OS was 20.7 months (95% CI, 9.2-20.7), with a six-month OS
    rate of 72.9 percent.

The safety profile of KEYTRUDA was consistent with that observed in
previously reported studies. In Cohorts 1, 2 and 3, Grade 3-5
treatment-related adverse events (TRAEs) occurred in 46 (18%), 19 (76%),
and 7 (23%) patients, respectively. In Cohort 1, Grade 3-5 TRAEs were
anemia (3%), fatigue (2%), and dehydration (1%); TRAEs led to
discontinuation in seven patients (3%) and death in two patients (1%).
In Cohort 2, Grade 3/4 TRAEs were neutropenia (24%), stomatitis (20%),
anemia (8%), decreased platelet count (8%), decreased appetite (8%), and
fatigue (8%). TRAEs in Cohort 2 led to discontinuation in three patients
(12%); there were no treatment-related deaths. In Cohort 3, Grade 3-5
TRAEs occurred in seven patients (23%); there was one treatment-related
death (3%) and no discontinuations due to TRAEs.

In Cohorts 1, 2 and 3, Grade 3 or higher immune-mediated adverse events
occurred in 13, four, and three patients, respectively. In Cohort 1,
Grade 3 immune-mediated adverse events were colitis (n=3), pneumonitis
(n=2), thyroiditis (n=1), and hypothyroidism (n=1); there were no Grade
4-5 immune-mediated adverse events. In Cohort 2, Grade 3 immune-mediated
adverse events were palmar-plantar erythrodysesthesia (n=2), nephrotic
syndrome (n=1), rash (n=1), and maculopapular rash (n=1); there were no
Grade 4-5 immune-mediated adverse events. In Cohort 3, Grade 3
immune-mediated adverse events were colitis (n=1) and rash (n=1); there
was one Grade 5 adverse event (pneumonitis).

About KEYNOTE-059

KEYNOTE-059 is a registrational, phase 2 non-randomized, multi-cohort
study (Cohorts 1, 2 and 3) investigating KEYTRUDA (pembrolizumab) in
patients with advanced gastric or GEJ adenocarcinoma. Patients in Cohort
1 received KEYTRUDA monotherapy after two or more prior lines of
therapy. Patients in Cohort 2 had received no prior therapy and received
KEYTRUDA in combination with cisplatin (80 mg/m2 Q3W) and
5-fluorouracil (800 mg/m2 Q3W) or capecitabine (in Japan
only, 1000 mg/m2 BID Q3W) as a first-line therapy. Patients
in Cohort 3, which only enrolled patients whose tumors were positive for
PD-L1, received KEYTRUDA monotherapy as a first-line therapy. In all
cohorts, KEYTRUDA was given at 200 mg every three weeks for up to 24
months. The primary endpoints are safety (all cohorts) and ORR using
Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Key
secondary endpoints are ORR and duration of response by RECIST v1.1,
PFS, and OS. Data from Cohorts 1 and 2 were further assessed based on
PD-L1 expression. Tumors were considered to have positive PD-L1
expression if the combined positive score (CPS) – as examined by tumor
and immune cells – was equal to or greater than one.

About Gastric Cancer

Gastric cancer, also called stomach cancer, is a type of cancer that
begins in the stomach and tends to develop slowly over many years. Most
gastric cancers are adenocarcinomas, which develop from the cells of the
innermost lining (mucosa) of the stomach. Risk factors for gastric
cancer include gender, age, ethnicity, geography and infection with Helicobacter
pylori
. Worldwide, gastric cancer is the fifth most common type of
cancer and the third leading cause of cancer death. Each year there are
approximately 952,000 newly diagnosed cases of gastric cancer resulting
in approximately 723,000 deaths worldwide.

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.

Studies of KEYTRUDA – from the largest immuno-oncology program in the
industry with more than 550 trials – include a wide variety of cancers
and treatment settings. The KEYTRUDA clinical program seeks to
understand factors that predict a patient’s likelihood of benefitting
from treatment with KEYTRUDA, including the exploration of several
different biomarkers across a broad range of tumors.

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 (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.

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 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
(pembrolizumab) 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
pediatric patients 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.

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 (pembrolizumab) 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
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 (pembrolizumab)
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 postmarketing 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 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 (pembrolizumab) 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.

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%). 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%).

When KEYTRUDA was administered in combination with carboplatin and
pemetrexed (carbo/pem), 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 (pembrolizumab) as compared to carbo/pem alone for any
specified adverse reaction.

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.

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 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 (pembrolizumab) 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 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 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

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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 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
Media Contacts:
Pamela Eisele, 267-305-3558
or
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or
Investor Contacts:
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or
Amy Klug, 908-740-1898

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