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March 14, 2018 6:30 pm ET

Late-Breaker Presentation of Overall Survival and Progression-Free Survival Results from Pivotal Phase 3 KEYNOTE-189 Trial with KEYTRUDA ^® (pembrolizumab) Plus Pemetrexed and Platinum Chemotherapy in First-Line Treatment of Advanced Nonsquamous Non-Small Cell Lung Cancer

First-Time KEYTRUDA Data Including Recurrence-Free Survival from Phase 3 KEYNOTE-054 Study, in Collaboration with EORTC, in Patients with Stage III Surgically Resected High-Risk Melanoma

Additional Research with KEYTRUDA, Investigational STING Agonist (MK-1454) and Merck’s Collaboration with AstraZeneca for LYNPARZA ^® (olaparib) to be Presented

Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced that new research from Merck’s broad oncology clinical
program – across several major tumor types, as monotherapy and in
combination – will be presented at the American Association for Cancer
Research (AACR) Annual Meeting 2018 in Chicago from April 14-18. For the
first time, data from the pivotal phase 3 KEYNOTE-189 trial with KEYTRUDA^®
(pembrolizumab), Merck’s anti-PD-1 therapy, in combination with
pemetrexed (ALIMTA^®) and cisplatin or carboplatin for the
first-line treatment of metastatic nonsquamous non-small cell lung
cancer (NSCLC) will be presented (Abstract #CT075). In January 2018,
Merck announced the KEYNOTE-189 study met its dual primary endpoints,
and the KEYTRUDA combination resulted in significantly longer overall
survival (OS) and progression-free survival (PFS) than pemetrexed plus
platinum chemotherapy alone. In addition, results from the phase 3
KEYNOTE-054 trial, in collaboration with the European Organization for
Research and Treatment of Cancer (EORTC), studying KEYTRUDA in adjuvant
melanoma will be presented (Abstract #CT001). As previously announced,
this is the first KEYTRUDA trial to demonstrate a significant
recurrence-free survival (RFS) benefit in the adjuvant treatment setting
for stage III melanoma.

“Our global efforts in immuno-oncology research, anchored by KEYTRUDA,
are fueled by a commitment to improve the lives of patients suffering
from malignant disease,” said Dr. Roger M. Perlmutter, president, Merck
Research Laboratories. “New studies to be presented at AACR, including
our KEYNOTE-189 and -054 trials in first-line lung cancer and adjuvant
melanoma, respectively, demonstrate the progress that we and our
colleagues have made in developing treatment regimens for a broad range
of cancers.”

“The science of immunotherapy has advanced significantly in recent
years, and Merck is forging new ground through its research efforts. At
the Cancer Research Institute, we support the discovery of new treatment
options for people with cancer and we are very excited about the new
research with KEYTRUDA in first-line lung cancer and other cancers to be
presented at AACR,” said Jill O’Donnell-Tormey, Ph.D., chief executive
officer and director of scientific affairs, Cancer Research Institute
(CRI).

With KEYTRUDA (pembrolizumab) and a growing early pipeline of 20 novel
mechanisms, Merck has become a leader in immuno-oncology research with
the largest clinical program in the industry. Data from Merck’s broad
portfolio including KEYTRUDA, internally-discovered investigational
STING agonist (MK-1454), and several collaborations including with
AstraZeneca for the PARP inhibitor LYNPARZA^® (olaparib), will
be featured in more than 20 oral plenary and poster presentations.

Select data highlights at AACR include:

• KEYNOTE-189: Randomized, double-blind, phase 3 study of
  pembrolizumab (pembro) or placebo plus pemetrexed (pem) and platinum
  as first-line therapy for metastatic NSCLC. Top-line results showed
  that the KEYTRUDA combination improved OS and PFS in the first-line
  treatment of nonsquamous NSCLC. Abstract #CT075. L Gandhi. Plenary
  Session: Monday, April 16, 10:30 a.m.-12:30 p.m. CDT.
• KEYNOTE-054 (EORTC1325): Pembrolizumab versus placebo after
  complete resection of high-risk stage III melanoma: Efficacy and
  safety results from the EORTC 1325-MG/KEYNOTE-054 double-blinded phase
  III trial. In January 2018, Merck and EORTC announced the study met
  the primary endpoint of RFS, showing significant benefit for patients
  with resected stage III melanoma who received KEYTRUDA compared to
  placebo. Abstract #CT001. A Eggermont. Plenary Session: Sunday, April
  15, 9:30 a.m.-12:15 p.m. CDT.
• KEYNOTE-040: Updated survival results of the KEYNOTE-040 study
  of pembrolizumab vs standard-of-care chemotherapy for recurrent or
  metastatic head and neck squamous cell carcinoma. Updated OS results
  will be presented at AACR. Abstract #CT115. D Soulières.
  Minisymposium: Monday, April 16, 3:00-5:00 p.m. CDT.
• Merck’s Early Pipeline: Combining STING Agonists with an
  Anti-PD-1 Antagonist results in Marked AntiTumor Activity in
  Immune-Excluded Tumors. MK-1454, Merck’s investigational STING
  (stimulator of interferon genes) agonist, is currently being evaluated
  in a phase 1 study as monotherapy and in combination with KEYTRUDA in
  patients with advanced solid tumors and lymphomas. Abstract #4721/24.
  S Perera. Poster Presentation: Tuesday, April 17, 1:00-5:00 p.m. CDT.
• OlympiAD: OlympiAD final overall survival: Olaparib versus
  chemotherapy treatment of physician’s choice (TPC) in patients with
  HER2-negative metastatic breast cancer (mBC) and a germline BRCA
  mutation (gBRCAm). Abstract #CT038. M Robson. Minisymposium:
  Sunday, April 15, 3:00-5:00 p.m. CDT.

Additional data to be presented for KEYTRUDA (pembrolizumab) and from
Merck’s collaboration with AstraZeneca for LYNPARZA (olaparib) include:

Additional KEYTRUDA Data at AACR

• Minisymposium: Safety, efficacy, and immune correlates of alternative
  doses and schedules of entinostat combined with pembrolizumab in
  patients with advanced solid tumors – results from SNDX-275-0141 Phase
  I trial. AW Tolcher.
• Minisymposium: Biomarkers predictive of response to pembrolizumab in
  head and neck cancer (HNSCC). TY Seiwert.
• Minisymposium: Effect of JAK/STAT or PI3Kδ plus PD-1 inhibition on the
  tumor microenvironment: Biomarker results from a phase 1b study in
  patients with advanced solid tumors. J.M. Kirkwood.
• Poster Presentation: Durability of responses to the combination of
  SD-101 and pembrolizumab in advanced metastatic melanoma: Results of a
  phase 1b, multicenter study. A Ribas.
• Poster Presentation: Phase Ib/II, open-label, multicenter study of
  intratumoral SD-101 in combination with pembrolizumab in anti-PD-1
  treatment-naïve patients with recurrent or metastatic head and neck
  squamous cell carcinoma (HNSCC). E Cohen.
• Poster Presentation: Imprime PGG, a soluble yeast β-glucan PAMP, in
  combination with Pembrolizumab induces infiltration and activation of
  both innate and adaptive immune cells within tumor sites in melanoma
  and triple-negative breast cancer (TNBC) patients. MT Uhlik.
• Poster Presentation: Comprehensive investigation of Programmed Death
  Receptor Ligand 1 (PD-L1) Expression and Associated Molecular Features
  in Gastric Cancer patients. X Liu.
• Poster Presentation: Molecular Biomarker Study of Programmed Death
  Receptor Ligand 1 (PD-L1) in Korean Patients with Lung Adenocarcinoma.
  X Liu.

Additional LYNPARZA Data at AACR

• Poster Presentation: A two-stage Simon Design phase II study for
  NOn-BRCA metastatic BReast cancer (MBC) patients with homologous
  recombination deficiency treated with OLAparib single agent. (NOBROLA
  study). E Aguirre.
• Poster Presentation: Testing a combination of AKT inhibitor (AZD5363)
  with PARP inhibitor Olaparib plus Carboplatin in TNBC. JH Carlson.
• Poster Presentation: Patient derived ovarian cancer xenograft (OC-PDX)
  to study the response of the PARP inhibitor olaparib. F Bizzaro.
• Poster Presentation: Adaptive oncology phase 1 study of first-in-class
  inhibitor of ataxia telangiectasia mutated protein kinase (ATM), in
  combination with olaparib. Y Chen.
• Poster Presentation: A pre-surgical window of opportunity study to
  investigate the biomarker effects of DNA damage response (DDR) agents
  in patients (pts) with Head and Neck Squamous Cell Carcinoma (HNSCC).
  U Duvvuri.
• Poster Presentation: The PARP inhibitor olaparib is synergistic with
  the ATR inhibitor AZD6738 in ATM deficient cancer cells. R Lloyd.
• Poster Session: A head-to-head comparison of the properties of five
  clinical PARP inhibitors identifies new insights that can explain both
  the observed clinical efficacy and safety profiles. E Leo.

For more information, including a complete list of abstract titles,
please see the AACR program at http://www.abstractsonline.com/pp8/#!/4562.

Merck Investor Event: Merck will hold an investor event in
conjunction with the 2018 AACR Annual Meeting on Monday, April 16 at
6:45 p.m. CDT (7:45 p.m. EDT). Those unable to attend in person will be
able to listen to a live audio webcast of the presentation. Details of
the event to be provided at a date closer to the event at http://investors.merck.com/home/default.aspx.

About KEYTRUDA

^® 

(pembrolizumab)
Injection 100mg

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

Merck has the industry’s largest immuno-oncology clinical research
program, which currently involves more than 700 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 (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 (pembrolizumab) 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 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 (pembrolizumab) 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
(pembrolizumab), 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 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
(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.

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 (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.

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
(pembrolizumab) as compared to carbo/pem alone for any specified adverse
reaction.

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

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

In KEYNOTE-052, KEYTRUDA 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.

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.

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

Indications for LYNPARZA

^®

(olaparib) in the
U.S.

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 (olaparib).

In patients with deleterious or suspected deleterious gBRCAm, human
epidermal growth factor receptor 2 (HER2)-negative metastatic breast
cancer who have previously been treated with chemotherapy in the
neoadjuvant, adjuvant or metastatic setting. Patients with hormone
receptor (HR)-positive breast cancer should have been treated with a
prior endocrine therapy or be considered inappropriate for endocrine
treatment. Select patients for therapy based on an FDA-approved
companion diagnostic for LYNPARZA.

Important Safety Information for LYNPARZA

^®


(olaparib)

Contraindications

There are no contraindications for LYNPARZA.

Warnings and Precautions

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred
in <1.5% of patients exposed to LYNPARZA 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 also had a
history of more than one primary malignancy or of bone marrow dysplasia.

Do not start LYNPARZA until patients have recovered from hematological
toxicity caused by previous chemotherapy (≤Grade 1). Monitor complete
blood count for cytopenia at baseline and monthly thereafter for
clinically significant changes during treatment. For prolonged
hematological toxicities, interrupt LYNPARZA and monitor blood count
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
(olaparib), 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 LYNPARZA treatment 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 following the last dose. Advise male patients
with female partners of reproductive potential or who are pregnant to
use effective contraception during treatment and for 3 months following
the last dose of LYNPARZA and to not donate sperm during this time.

Adverse Reactions—Maintenance Setting

Most common adverse reactions (Grades 1-4) in ≥20% of patients in
clinical trials of LYNPARZA (olaparib) 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 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 (olaparib) for advanced gBRCAm
ovarian cancer (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%).

Adverse Reactions—gBRCAm, HER2-Negative Breast Cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients
in OlympiAD were: nausea (58%), anemia (40%), fatigue (including
asthenia) (37%), vomiting (30%), neutropenia (27%), respiratory tract
infection (27%), leukopenia (25%), diarrhea (21%), and headache (20%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients
in OlympiAD were: decrease in hemoglobin (82%), decrease in lymphocytes
(73%), decrease in leukocytes (71%), increase in mean corpuscular volume
(71%), decrease in absolute neutrophil count (46%), and decrease in
platelets (33%).

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 (olaparib). If a moderate inducer cannot be
avoided, there is a potential for decreased efficacy of LYNPARZA.

Use in Specific Populations

Lactation: No data are available regarding the presence of
olaparib in human milk, its effects on the breastfed infant or 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 (olaparib) and for 1 month after receiving the
final dose.

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

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).

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.

About the AstraZeneca and Merck Strategic Oncology Collaboration

In July 2017, AstraZeneca and Merck (known as MSD outside the United
States and Canada) announced a global strategic oncology collaboration
to co-develop and co-commercialize LYNPARZA, 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.

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 2017 Annual Report on Form 10-K
and the company’s other filings with the Securities and Exchange
Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

Please see Prescribing Information for KEYTRUDA (pembrolizumab) at


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


and

Patient Information/Medication Guide for KEYTRUDA at

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

.

Please see complete Prescribing Information for LYNPARZA (olaparib)
tablets


https://www.azpicentral.com/lynparza_tb/pi_lynparza_tb.pdf#page=1


and complete

Prescribing Information for LYNPARZA capsules,


https://www.azpicentral.com/Lynparza/pi_lynparza.pdf#page=1


including Patient Information (Medication Guides).

ALIMTA^® is a registered trademark of Eli Lilly and Company.

Merck
Media:
Pamela Eisele, 267-305-3558
or
Courtney Ronaldo, 908-740-6132
or
Investors:
Teri Loxam, 908-740-1986
or
Michael DeCarbo, 908-740-1807