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September 10, 2017 7:45 am ET

Updated Data from Phase 3 KEYNOTE-045 Trial to Be Presented at ESMO 2017 Congress

KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE: MRK), known as MSD outside the United States and Canada,
today announced updated results from the phase 3 KEYNOTE-045 trial
evaluating KEYTRUDA^® (pembrolizumab), the company’s anti-PD-1
therapy, in patients with locally advanced or metastatic urothelial
carcinoma (a type of bladder cancer) with disease progression on or
after platinum-containing chemotherapy (post-platinum failure). Updated
data show that with median follow-up of 22.5 months, KEYTRUDA continues
to demonstrate an overall survival (OS) benefit over investigator’s
choice of paclitaxel, docetaxel or vinflunine as a second-line therapy,
post-platinum failure, regardless of PD-L1 expression (HR, 0.70 [95% CI,
0.57-0.86], p=0.0003). Findings are being presented at the European
Society for Medical Oncology (ESMO) 2017 Congress in Madrid, Spain, on
Sunday, Sept. 10 (poster from 2:45 – 4:15 p.m. CEST; discussion: 3:15 –
3:45 p.m. CEST) (Location: Cordoba Auditorium) (Abstract #LBA37_PR).

“These data at ESMO provide further insights and greater understanding
in using KEYTRUDA in select second-line advanced urothelial carcinoma
treatment settings, and importantly, demonstrate an overall survival
advantage with KEYTRUDA compared to standard chemotherapy agents
vinflunine, docetaxel and paclitaxel, which are common in clinical
practice for the treatment of this disease,” said professor Ronald de
Wit, M.D., Ph.D., group leader experimental systemic therapy of
urogenital cancers, Erasmus MC Cancer Institute. “For previously treated
patients, post-platinum failure, these findings are also encouraging as
they show an overall survival benefit regardless of PD-L1 status or
choice of commonly used chemotherapy.”

“With nearly two years follow-up, these updated phase 3 data continue to
show an overall survival benefit with KEYTRUDA in patients with advanced
urothelial carcinoma whose cancer has progressed after receiving
previous treatment for their disease,” said Dr. Roger Dansey, senior
vice president and therapeutic area head, oncology late-stage
development, Merck Research Laboratories. “We are pleased that, with the
approval in the U.S. and recent approval of KEYTRUDA in the EU, more
patients now have an important treatment option available to them.”

Currently, Merck also has the largest immuno-oncology clinical
development program in bladder cancer, with 29 trials underway involving
KEYTRUDA (pembrolizumab) as monotherapy and in combination, including
four registration-enabling studies.

Data in Second-Line Post-Platinum Failure Patients, KEYNOTE-045

KEYNOTE-045 is an open-label, randomized phase 3 trial of KEYTRUDA
compared to investigator’s choice of chemotherapy (paclitaxel, docetaxel
or vinflunine) in patients with locally advanced or metastatic
urothelial cancer with disease progression on or after
platinum-containing chemotherapy. The trial was prematurely stopped
after a pre-planned interim analysis demonstrated significantly longer
OS with KEYTRUDA compared to chemotherapy (median follow-up, 14.1
months). Efficacy was assessed in the overall study population (n=542),
as well as in patients with PD-L1 expression – defined as a combined
positive score of 10 or more (CPS ≥10) (KEYTRUDA arm: n=74/270;
chemotherapy arm; n=90/272) (additional details on the trial design are
provided below).

Data presented at ESMO (Abstract #LBA37_PR) include four months of
additional follow-up (data cut-off, May 19, 2017; median follow up, 22.5
months) and continue to show a superior OS advantage with KEYTRUDA
compared to chemotherapy in the second-line setting, regardless of PD-L1
expression. In the overall study population, data show a 30 percent
reduction in the risk of death with KEYTRUDA (HR, 0.70 [95% CI,
0.57-0.86], p=0.0003), the median OS was 10.3 months with KEYTRUDA (95%
CI, 8.0-12.3) and 7.4 months with chemotherapy (95% CI, 6.3-8.3), and
the 18-month OS rate was 33.2 percent with KEYTRUDA compared to 19.7
percent with chemotherapy. Analysis of OS based on PD-L1 expression show
a 42 percent reduction in the risk of death with KEYTRUDA (HR, 0.58 [95%
CI, 0.39-0.86], p=0.0029) in patients whose tumors expressed PD-L1 (CPS
≥10), the median OS was 8.0 months with KEYTRUDA (95% CI, 5.0-12.3) and
5.2 months with chemotherapy (95% CI, 4.2-7.5), and the 18-month OS rate
was 30.0 percent with KEYTRUDA compared to 16.9 percent with
chemotherapy.

As previously reported, there was no significant difference in
progression-free-survival (PFS) between treatment arms in the overall
study population (HR, 0.96 [95% CI, 0.79-1.16], p=0.32). The median PFS
was 2.1 months with KEYTRUDA (95% CI, 2.0-2.2) and 3.3 months with
chemotherapy (95% CI, 2.4-3.5); the 18-month PFS rate was 15.3 percent
with KEYTRUDA (pembrolizumab) compared to 4.8 percent with chemotherapy.
In patients whose tumors expressed PD-L1 (CPS ≥10), the median PFS was
2.1 months with KEYTRUDA (95% CI, 1.9-2.1) and 3.2 months with
chemotherapy (95% CI, 2.2-3.5); the 18-month PFS rate was 16.3 percent
with KEYTRUDA compared to 5.3 percent with chemotherapy (HR, 0.93 [95%
CI, 0.65-1.33], p=0.32).

Analyses of the secondary endpoints showed nearly double the overall
response rate (ORR) with KEYTRUDA compared to chemotherapy in the
overall study population, with an ORR of 21.1 percent in the KEYTRUDA
arm (complete response rate (CR) of 7.8 percent and a partial response
rate (PR) of 13.3 percent) and 11.0 percent in the chemotherapy arm (CR
of 2.9 percent and a PR of 8.1 percent). The median time to response was
2.1 months in both treatment arms; 57.9 percent of responses in the
KEYTRUDA arm were ongoing at the time of analysis compared to 20.0
percent in the chemotherapy arm. Median duration of response in patients
with partial or complete responses had not yet been reached in the
KEYTRUDA arm at the time of analysis (range: 1.6+ to 24.6+) with 67.0
percent of responses ongoing at 12 months (calculated per Kaplan-Meier
curve); in the chemotherapy arm, the median duration of response was 4.4
months (range: 1.4+ to 24.0+) with 35.0 percent of responses ongoing at
12 months (calculated per Kaplan-Meier curve).

In patients whose tumors expressed PD-L1, the ORR was 20.3 percent in
the KEYTRUDA arm (CR of 6.8 percent and a PR of 13.5 percent) and 6.7
percent in the chemotherapy arm (CR of 2.2 percent and a PR of 4.4
percent). The median time to response was 2.0 months in the KEYTRUDA arm
and 2.1 months in the chemotherapy arm; 73.3 percent of responses in the
KEYTRUDA arm were ongoing at the time of analysis compared to 33.3
percent in the chemotherapy arm. The median duration of response in
patients with partial or complete responses had not yet been reached in
the KEYTRUDA arm at the time of analysis (range: 1.6+ to 23.5+) with
77.0 percent of responses ongoing at 12 months (calculated per
Kaplan-Meier curve); in the chemotherapy arm, the median duration of
response was 4.4 months (range: 1.5+ to 20.8+) with 40.0 percent of
responses ongoing at 12 months (calculated per Kaplan-Meier curve).

A second abstract including a subgroup analysis from KEYNOTE-045
(Abstract #851PD) was also accepted as a poster at ESMO and provides
greater insight into the OS advantage with KEYTRUDA compared to the
individual chemotherapy agents. The retrospective analysis showed a 27
percent reduction in the risk of death versus paclitaxel (HR, 0.73 [95%
CI, 0.55-0.96]), a 21 percent reduction in the risk of death versus
docetaxel (HR, 0.79 [95% CI, 0.59-1.07]), and a 35 percent reduction in
the risk of death versus vinflunine (HR, 0.65 [95% CI, 0.49-0.87]). No
statistically significant difference in PFS was seen between KEYTRUDA
and each chemotherapy agent. Analyses of the secondary endpoints showed
an ORR of 11.9 percent, 6.0 percent, and 17.2 percent with paclitaxel,
docetaxel, and vinflunine, respectively, compared to 21.1 percent in the
KEYTRUDA (pembrolizumab) arm.

The safety profile of KEYTRUDA was consistent with that observed in
previously reported studies. Treatment-related adverse events (TRAEs) of
any grade occurred in 62.0 percent in the KEYTRUDA arm and 90.6 percent
in the chemotherapy arm. Grade 3 or higher TRAEs occurred in 16.5
percent and 50.2 percent of KEYTRUDA and chemotherapy patients,
respectively. Immune-mediated adverse events occurred in 19.5 percent of
patients in the KEYTRUDA arm and 7.5 percent in the chemotherapy arm.
The discontinuation rate due to treatment-related adverse events was 7.1
percent of patients in the KEYTRUDA arm and 12.5 percent of patients in
the chemotherapy arm. Deaths due to treatment-related adverse events
occurred in four patients treated with KEYTRUDA, one patient treated
with paclitaxel, and three patients treated with vinflunine.

About KEYNOTE-045

In KEYNOTE-045, patients were randomized to receive either KEYTRUDA 200
mg every three weeks (n=270) or investigator’s choice of any of the
following chemotherapy regimens, all given intravenously, every three
weeks (n=272): paclitaxel 175 mg/m², docetaxel 75 mg/m²,
or vinflunine 320 mg/m². The dual primary endpoints were OS
and PFS, as assessed by blinded independent central review (BICR) per
RECIST (Response Evaluation Criteria in Solid Tumors) v1.1; key
secondary endpoints included ORR, as assessed by BICR per RECIST 1.1,
duration of response and safety. Efficacy was assessed in all patients,
as well as in patients with PD-L1 expression.

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 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 (pembrolizumab) 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
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 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 (pembrolizumab) 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 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
(pembrolizumab) 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 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 (pembrolizumab) 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 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 (pembrolizumab) 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 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 (pembrolizumab) 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

and connect with us on Twitter, Facebook, Instagram,
YouTube
and LinkedIn.

Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA

This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the
“company”) includes “forward-looking statements” within the meaning of
the safe harbor provisions of the U.S. Private Securities Litigation
Reform Act of 1995. These statements are based upon the current beliefs
and expectations of the company’s management and are subject to
significant risks and uncertainties. There can be no guarantees with
respect to pipeline products that the products will receive the
necessary regulatory approvals or that they will prove to be
commercially successful. If underlying assumptions prove inaccurate or
risks or uncertainties materialize, actual results may differ materially
from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry
conditions and competition; general economic factors, including interest
rate and currency exchange rate fluctuations; the impact of
pharmaceutical industry regulation and health care legislation in the
United States and internationally; global trends toward health care cost
containment; technological advances, new products and patents attained
by competitors; challenges inherent in new product development,
including obtaining regulatory approval; the company’s ability to
accurately predict future market conditions; manufacturing difficulties
or delays; financial instability of international economies and
sovereign risk; dependence on the effectiveness of the company’s patents
and other protections for innovative products; and the exposure to
litigation, including patent litigation, and/or regulatory actions.

The company undertakes no obligation to publicly update any
forward-looking statement, whether as a result of new information,
future events or otherwise. Additional factors that could cause results
to differ materially from those described in the forward-looking
statements can be found in the company’s 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:
Pamela Eisele, 267-305-3558
or
Courtney Ronaldo, 908-740-6132
or
Investors
Teri Loxam, 908-740-1986
or
Amy Klug, 908-740-1898