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November 30, 2017 7:00 am ET

Efficacy Data from Phase 2 KEYNOTE-086 Trial, Cohort B, for KEYTRUDA Monotherapy in Patients with Untreated Metastatic Triple-Negative Breast Cancer to Be Featured in Spotlight Session

Merck (NYSE: MRK), known as MSD outside the United States and Canada,
today announced that new and updated data from six abstracts
investigating KEYTRUDA^® (pembrolizumab), the company’s
anti-PD-1 therapy, as both monotherapy and combination therapy, across a
range of difficult-to-treat breast cancers, will be presented at the
2017 San Antonio Breast Cancer Symposium (SABCS), Dec. 5 – 9. In
addition to the presentation of KEYTRUDA data at SABCS, updated data on
LYNPARZA^® (olaparib), the first-in-class poly ADP-ribose
polymerase (PARP) inhibitor being co-developed and co-commercialized
with AstraZeneca, will be presented.

KEYTRUDA presentations include a Spotlight Session with findings from
the phase 2 KEYNOTE-086 trial, Cohort B, investigating KEYTRUDA as a
monotherapy in previously untreated patients with metastatic
triple-negative breast cancer (TNBC) whose tumors express PD-L1
(Abstract #PD6-10). In the combination setting, KEYTRUDA data highlights
at SABCS include:

• Final results from the phase 1b/2 KEYNOTE-014 (PANACEA) trial
  investigating KEYTRUDA in combination with trastuzumab in
  trastuzumab-resistant HER2-positive metastatic breast cancer (Abstract
  #GS2-06);
• Two new biomarker analyses from the ongoing phase 2 I-SPY 2 trial
  (Abstract #PD6-08, Abstract #PD6-14); and,
• Updated data from the phase 1b/2 KEYNOTE-150 (ENHANCE-1) trial
  investigating KEYTRUDA (pembrolizumab) in combination with
  Eisai Co., Ltd.’s microtubule dynamics inhibitor, eribulin mesylate
  (product name: Halaven^®, “eribulin”), in patients with
  metastatic TNBC (Abstract #PD6-13).

Data investigating LYNPARZA (olaparib) as monotherapy will also be
presented. Findings include additional data from the pivotal phase 3
OlympiAD trial investigating LYNPARZA versus chemotherapy in patients
with HER2-negative metastatic breast cancer and a germline BRCA mutation
(Abstract #P5-21-12), as well as a subgroup analysis in Asian patients
(Abstract #P5-21-13).

“We have seen significant therapeutic advances over the years in the
field of breast cancer; however, there remains significant unmet medical
need, particularly in certain categories of the disease,” said Dr. Roy
Baynes, senior vice president and head of global clinical development,
chief medical officer, Merck Research Laboratories. “Through our
comprehensive clinical program studying KEYTRUDA, as well as LYNPARZA,
we hope to bring additional therapeutic benefit to breast cancer
patients.”

A select list of the KEYTRUDA-related abstracts accepted for
presentation at SABCS are included below. For a complete list of
KEYTRUDA and LYNPARZA abstract titles, please visit the SABCS website.

KEYTRUDA-Related Data at SABCS

Monotherapy Abstracts:

• Abstract #PD6-10 Spotlight Session: KEYNOTE-086 cohort B:
  Pembrolizumab monotherapy for PD-L1-positive, previously untreated,
  metastatic triple-negative breast cancer (mTNBC). Adams S. Thursday,
  Dec. 7. 5:00 p.m. – 7:00 p.m. CT. Location: Stars at Night Ballroom 3
  & 4.

Combination Abstracts:

• Abstract #GS2-06 Oral Presentation: Phase Ib/II study evaluating
  safety and efficacy of pembrolizumab and trastuzumab in patients with
  trastuzumab-resistant HER2-positive metastatic breast cancer: Results
  from the PANACEA (IBCSG 45-13/BIG 4-13/KEYNOTE-014) study. Loi S.
  Wednesday, Dec. 6. 4:30 p.m. CT. Location: Hall 3.
• Abstract #PD6-13 Spotlight Session: Phase 1b/2 study to
  evaluate eribulin mesylate in combination with pembrolizumab in
  patients with metastatic triple-negative breast cancer. Tolaney SM.
  Thursday, Dec. 7. 5:00 p.m. – 7:00 p.m. CT. Location: Stars at Night
  Ballroom 3 & 4.
• Abstract #PD6-08 Spotlight Session: Analysis of immune infiltrates
  (assessed via multiplex fluorescence immunohistochemistry) and immune
  gene expression signatures as predictors of response to the checkpoint
  inhibitor pembrolizumab in the neoadjuvant I-SPY 2 trial. Campbell
  M. Thursday, Dec. 7. 5:00 p.m. – 7:00 p.m. CT. Location: Stars at
  Night Ballroom 3 & 4.
• Abstract #PD6-14 Spotlight Session: Analysis of DNA repair
  deficiency biomarkers as predictors of response to the PD1 inhibitor
  pembrolizumab: Results from the neoadjuvant I-SPY 2 TRIAL for Stage
  II-III high-risk breast cancer. Yau C. Thursday, Dec. 7. 5:00 p.m. –
  7:00 p.m. CT. Location: Stars at Night Ballroom 3 & 4.
• Abstract #P1-09-01 Poster Session: A phase 1b study of abemaciclib
  plus pembrolizumab for patients with hormone receptor-positive (HR+),
  human epidermal growth factor receptor 2-negative (HER2-) metastatic
  breast cancer (MBC). Rugo HS. Wednesday, Dec. 6. 5:00 p.m. – 7:00 p.m.
  CT. Location: Hall 1.

The KEYTRUDA (pembrolizumab) breast cancer clinical development program
encompasses 15 internal and external collaborative studies across
multiple breast cancer subtypes including four registration-enabling
studies in TNBC (KEYNOTE-119, KEYNOTE-355, KEYNOTE-242 and KEYNOTE-522),
and 11 other studies evaluating KEYTRUDA either in monotherapy or in
combination with other anti-cancer treatments.

About the AstraZeneca and Merck Strategic Oncology Collaboration

On July 27, 2017, AstraZeneca and Merck, announced a global strategic
oncology collaboration to co-develop and co-commercialize AstraZeneca’s
LYNPARZA (olaparib), the world’s first PARP inhibitor, and potential new
medicine selumetinib, a MEK inhibitor, for multiple cancer types. The
collaboration is based on increasing evidence that PARP and MEK
inhibitors can be combined with PD-L1/PD-1 inhibitors for a range of
tumor types. Working together, the companies will jointly develop
LYNPARZA and selumetinib in combination with other potential new
medicines and as a monotherapy. Independently, the companies will
develop LYNPARZA and selumetinib in combination with their respective
PD-L1 and PD-1 medicines.

About KEYTRUDA

^® 

(pembrolizumab)
Injection 100 mg

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

Merck has the industry’s largest immuno-oncology clinical research
program, which currently involves more than 650 trials studying KEYTRUDA
across a wide variety of cancers and treatment settings. The KEYTRUDA
clinical program seeks to understand the role of KEYTRUDA across cancers
and the factors that may predict a patient’s likelihood of benefitting
from treatment with KEYTRUDA, including exploring several different
biomarkers.

KEYTRUDA (pembrolizumab) Indications and Dosing

Melanoma

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

Lung Cancer

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

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

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

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

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

Gastric Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent
locally advanced or metastatic gastric or gastroesophageal junction
(GEJ) adenocarcinoma whose tumors express PD-L1 [Combined Positive Score
(CPS) ≥1] as determined by an FDA-approved test, with disease
progression on or after two or more prior lines of therapy including
fluoropyrimidine- and platinum-containing chemotherapy and if
appropriate, HER2/neu-targeted therapy. This indication is approved
under accelerated approval based on tumor response rate and durability
of response. Continued approval for this indication may be contingent
upon verification and description of clinical benefit in the
confirmatory trials. The recommended dose of KEYTRUDA is 200 mg every
three weeks until disease progression, unacceptable toxicity, or up to
24 months in patients without disease progression.

Selected Important Safety Information for KEYTRUDA

^®
 (pembrolizumab)

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases.
Pneumonitis occurred in 94 (3.4%) of 2799 patients receiving KEYTRUDA,
including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%)
pneumonitis, and occurred more frequently in patients with a history of
prior thoracic radiation (6.9%) compared to those without (2.9%).
Monitor patients for signs and symptoms of pneumonitis. Evaluate
suspected pneumonitis with radiographic imaging. Administer
corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA
for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or
recurrent Grade 2 pneumonitis.

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 48
(1.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.4%), 3
(1.1%), and 4 (<0.1%) colitis. Monitor patients for signs and symptoms
of colitis. Administer corticosteroids for Grade 2 or greater colitis.
Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for
Grade 4 colitis.

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 19
(0.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3
(0.4%), and 4 (<0.1%) hepatitis. Monitor patients for changes in liver
function. Administer corticosteroids for Grade 2 or greater hepatitis
and, based on severity of liver enzyme elevations, withhold or
discontinue KEYTRUDA.

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

KEYTRUDA can cause thyroid disorders, including hyperthyroidism,
hypothyroidism, and thyroiditis. Hyperthyroidism occurred in 96 (3.4%)
of 2799 patients receiving KEYTRUDA, including Grade 2 (0.8%) and 3
(0.1%) hyperthyroidism. Hypothyroidism occurred in 237 (8.5%) of 2799
patients receiving KEYTRUDA, including Grade 2 (6.2%) and 3 (0.1%)
hypothyroidism. The incidence of new or worsening hypothyroidism was
higher in patients with HNSCC, occurring in 28 (15%) of 192 patients
with HNSCC, including Grade 3 (0.5%) hypothyroidism. Thyroiditis
occurred in 16 (0.6%) of 2799 patients receiving KEYTRUDA, including
Grade 2 (0.3%) thyroiditis. Monitor patients for changes in thyroid
function (at the start of treatment, periodically during treatment, and
as indicated based on clinical evaluation) and for clinical signs and
symptoms of thyroid disorders. Administer replacement hormones for
hypothyroidism and manage hyperthyroidism with thionamides and
beta-blockers as appropriate. Withhold or discontinue KEYTRUDA
(pembrolizumab) 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 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.

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 (pembrolizumab). 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.

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.

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

In KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to adverse
reactions in 8% of 682 patients with metastatic NSCLC. The most common
adverse event resulting in permanent discontinuation of KEYTRUDA was
pneumonitis (1.8%). Adverse reactions leading to interruption of
KEYTRUDA occurred in 23% of patients; the most common (≥1%) were
diarrhea (1%), fatigue (1.3%), pneumonia (1%), liver enzyme elevation
(1.2%), decreased appetite (1.3%), and pneumonitis (1%). The most common
adverse reactions (occurring in at least 20% of patients and at a higher
incidence than with docetaxel) were decreased appetite (25% vs 23%),
dyspnea (23% vs 20%), and nausea (20% vs 18%).

In KEYNOTE-021(G1), when KEYTRUDA was administered in combination with
carboplatin and pemetrexed (carbo/pem) in advanced nonsquamous NSCLC,
KEYTRUDA was discontinued in 10% of 59 patients. The most common adverse
reaction resulting in discontinuation of KEYTRUDA (≥2%) was acute kidney
injury (3.4%). Adverse reactions leading to interruption of KEYTRUDA
occurred in 39% of patients; the most common (≥2%) were fatigue (8%),
neutrophil count decreased (8%), anemia (5%), dyspnea (3.4%), and
pneumonitis (3.4%).The most common adverse reactions (≥20%) with
KEYTRUDA compared to carbo/pem alone were fatigue (71% vs 50%), nausea
(68% vs 56%), constipation (51% vs 37%), rash (42% vs 21%), vomiting
(39% vs 27%), dyspnea (39% vs 21%), diarrhea (37% vs 23%), decreased
appetite (31% vs 23%), headache (31% vs 16%), cough (24% vs 18%),
dizziness (24% vs 16%), insomnia (24% vs 15%), pruritus (24% vs 4.8%),
peripheral edema (22% vs 18%), dysgeusia (20% vs 11%), alopecia (20% vs
3.2%), upper respiratory tract infection (20% vs 3.2%), and arthralgia
(15% vs 24%). This study was not designed to demonstrate a statistically
significant difference in adverse reaction rates for KEYTRUDA as
compared to carbo/pem alone for any specified adverse reaction.

In KEYNOTE-012, KEYTRUDA was discontinued due to adverse reactions in
17% of 192 patients with HNSCC. Serious adverse reactions occurred in
45% of patients. The most frequent serious adverse reactions reported in
at least 2% of patients were pneumonia, dyspnea, confusional state,
vomiting, pleural effusion, and respiratory failure. The most common
adverse reactions (reported in at least 20% of patients) were fatigue,
decreased appetite, and dyspnea. Adverse reactions occurring in patients
with HNSCC were generally similar to those occurring in patients with
melanoma or NSCLC, with the exception of increased incidences of facial
edema (10% all Grades; 2.1% Grades 3 or 4) and new or worsening
hypothyroidism.

In KEYNOTE-087, KEYTRUDA (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.

It is not known whether KEYTRUDA (pembrolizumab) is excreted in human
milk. Because many drugs are excreted in human milk, instruct women to
discontinue nursing during treatment with KEYTRUDA and for 4 months
after the final dose.

There is limited experience in pediatric patients. In a study, 40
pediatric patients (16 children aged 2 years to younger than 12 years
and 24 adolescents aged 12 years to 18 years) with advanced melanoma,
lymphoma, or PD-L1–positive advanced, relapsed, or refractory solid
tumors were administered KEYTRUDA 2 mg/kg every 3 weeks. Patients
received KEYTRUDA for a median of 3 doses (range 1–17 doses), with 34
patients (85%) receiving KEYTRUDA for 2 doses or more. The safety
profile in these 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%).

About LYNPARZA

^®

(olaparib)

LYNPARZA was the first FDA-approved oral poly ADP-ribose polymerase
(PARP) inhibitor that may exploit tumor DNA damage response (DDR)
pathway deficiencies to potentially kill cancer cells. Specifically, in
vitro studies have shown that olaparib-induced cytotoxicity may involve
inhibition of PARP enzymatic activity and increased formation of
PARP-DNA complexes, resulting in DNA damage and cancer cell death.

IMPORTANT SAFETY INFORMATION FOR LYNPARZA

^®

(olaparib)

DOSING AND ADMINISTRATION

To avoid substitution errors and overdose, do not substitute LYNPARZA
tablets with LYNPARZA capsules on a milligram-to-milligram basis due
to differences in the dosing and bioavailability of each formulation.
Recommended tablet dose is 300 mg, taken orally twice daily, with or
without food. Continue treatment until disease progression or
unacceptable toxicity. For adverse reactions, consider dose interruption
or dose reduction.

WARNINGS AND PRECAUTIONS

There are no contraindications for LYNPARZA.

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred
in <1.5% of patients exposed to LYNPARZA (olaparib) monotherapy, and the
majority of events had a fatal outcome. The duration of therapy in
patients who developed secondary MDS/AML varied from <6 months to >2
years. All of these patients had previous chemotherapy with platinum
agents and/or other DNA-damaging agents, including radiotherapy, and
some of these patients also had a history of previous cancer or bone
marrow dysplasia.

Do not start LYNPARZA until patients have recovered from hematological
toxicity caused by previous chemotherapy (≤Grade 1). Monitor complete
blood counts for cytopenia at baseline and monthly thereafter for
clinically significant changes during treatment. For prolonged
hematological toxicities, interrupt LYNPARZA and monitor blood counts
weekly until recovery. If the levels have not recovered to Grade 1 or
less after 4 weeks, refer the patient to a hematologist for further
investigations, including bone marrow analysis and blood sample for
cytogenetics. Discontinue LYNPARZA if MDS/AML is confirmed.

Pneumonitis: Occurred in <1% of patients exposed to LYNPARZA, and
some cases were fatal. If patients present with new or worsening
respiratory symptoms such as dyspnea, cough, and fever, or a
radiological abnormality occurs, interrupt treatment with LYNPARZA and
initiate prompt investigation. Discontinue LYNPARZA if pneumonitis is
confirmed and treat patient appropriately.

Embryo-Fetal Toxicity: Based on its mechanism of action and
findings in animals, LYNPARZA can cause fetal harm. A pregnancy test is
recommended for females of reproductive potential prior to initiating
treatment. Advise females of reproductive potential of the potential
risk to a fetus and to use effective contraception during treatment and
for 6 months after receiving the final dose.

ADVERSE REACTIONS—Maintenance Setting

Most common adverse reactions (Grades 1-4) in ≥20% of patients in
clinical trials of LYNPARZA in the maintenance setting for SOLO-2: nausea
(76%), fatigue (including asthenia) (66%), anemia (44%), vomiting (37%),
nasopharyngitis/upper respiratory tract infection (URI)/influenza (36%),
diarrhea (33%), arthralgia/myalgia (30%), dysgeusia (27%), headache
(26%), decreased appetite (22%), and stomatitis (20%).

Study 19: nausea (71%), fatigue (including asthenia) (63%),
vomiting (35%), diarrhea (28%), anemia (23%), respiratory tract
infection (22%), constipation (22%), headache (21%), and decreased
appetite (21%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in
clinical trials of LYNPARZA (olaparib) in the maintenance
setting (SOLO-2/Study 19) were: increase in mean corpuscular volume
(89%/82%), decrease in hemoglobin (83%/82%), decrease in leukocytes
(69%/58%), decrease in lymphocytes (67%/52%), decrease in absolute
neutrophil count (51%/47%), increase in serum creatinine (44%/45%), and
decrease in platelets (42%/36%).

ADVERSE REACTIONS—Advanced gBRCAm ovarian cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients in
clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer
after 3 or more lines of chemotherapy (pooled from 6 studies) were:
fatigue (including asthenia) (66%), nausea (64%), vomiting (43%), anemia
(34%), diarrhea (31%), nasopharyngitis/upper respiratory tract infection
(URI) (26%), dyspepsia (25%), myalgia (22%), decreased appetite (22%),
and arthralgia/musculoskeletal pain (21%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in
clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer
after 3 or more lines of chemotherapy (pooled from 6 studies) were:
decrease in hemoglobin (90%), increase in mean corpuscular volume (57%),
decrease in lymphocytes (56%), increase in serum creatinine (30%),
decrease in platelets (30%), and decrease in absolute neutrophil count
(25%).

DRUG INTERACTIONS

Anticancer Agents: Clinical studies of LYNPARZA in combination
with other myelosuppressive anticancer agents, including DNA-damaging
agents, indicate a potentiation and prolongation of myelosuppressive
toxicity.

CYP3A Inhibitors: Avoid concomitant use of strong or moderate
CYP3A inhibitors. If a strong or moderate CYP3A inhibitor must
be co-administered, reduce the dose of LYNPARZA. Advise patients to
avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange
juice during LYNPARZA treatment.

CYP3A Inducers: Avoid concomitant use of strong or moderate CYP3A
inducers when using LYNPARZA. If a moderate inducer cannot be avoided,
be aware of a potential for decreased efficacy of LYNPARZA.

USE IN SPECIFIC POPULATIONS

Pediatric Use: The safety and efficacy of LYNPARZA (olaparib)
have not been established in pediatric patients.

Lactation: No data are available regarding the presence of
olaparib in human milk, the effects on the breastfed infant, or the
effects on milk production. Because of the potential for serious adverse
reactions in the breastfed infant, advise a lactating woman not to
breastfeed during treatment with LYNPARZA and for 1 month after
receiving the final dose.

Hepatic Impairment: No adjustment to the starting dose is
required in patients with mild hepatic impairment (Child-Pugh
classification A). There are no data in patients with moderate or severe
hepatic impairment.

Renal Impairment: No adjustment to the starting dose is necessary
in patients with mild renal impairment (CLcr 51-80 mL/min). In patients
with moderate renal impairment (CLcr 31-50 mL/min), reduce the dose to
200 mg twice daily. There are no data in patients with severe renal
impairment or end-stage renal disease (CLcr ≤30 mL/min).

APPROVED USES for LYNPARZA (olaparib)

LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:

• For the maintenance treatment of adult patients with recurrent
  epithelial ovarian, fallopian tube, or primary peritoneal cancer, who
  are in complete or partial response to platinum-based chemotherapy
• For the treatment of adult patients with deleterious or suspected
  deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who
  have been treated with 3 or more prior lines of chemotherapy. Select
  patients for therapy based on an FDA-approved companion diagnostic for
  LYNPARZA

Merck’s 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

.

Please see complete 

Prescribing
Information

for LYNPARZA, including Patient Information
(Medication Guide)

Merck
Media:
Pamela Eisele, 267-305-3558
or
Ann Bush, 908-740-6677
or
Investors:
Teri Loxam, 908-740-1986
or
Michael DeCarbo, 908-740-1807