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May 15, 2019 4:00 pm ET

First-Time Data from POLO Trial Evaluating LYNPARZA ^® (olaparib) in Germline BRCA-Mutated Metastatic Pancreatic Cancer in Plenary Session and ASCO Press Program

KEYTRUDA ^® (pembrolizumab) Five-Year Survival Data in Advanced Non-Small Cell Lung Cancer (NSCLC) from KEYNOTE-001 Trial in ASCO Press Program

Overall Survival Data for KEYTRUDA in Metastatic Renal Cell Carcinoma (RCC), Recurrent/Metastatic Head and Neck Cancer and Advanced Gastric or Gastroesophageal Junction (GEJ) Cancer

KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE: MRK), known as MSD outside the United States and Canada,
today announced that new research from the company’s broad oncology
clinical development program will be presented at the 55^th
Annual Meeting of the American Society of Clinical Oncology (ASCO) in
Chicago from May 31-June 4. More than 140 abstracts have been accepted
evaluating Merck’s medicines – including KEYTRUDA, Merck’s anti-PD-1
therapy, LYNPARZA (in collaboration with AstraZeneca) and LENVIMA (in
collaboration with Eisai) – in over 25 types of cancer. LYNPARZA data
include new findings in metastatic pancreatic cancer with the first
presentation of results from the POLO study to be featured in the ASCO
Plenary Session and press program. Additionally, new or updated overall
survival (OS) findings for KEYTRUDA in non-small cell lung cancer
(NSCLC), renal cell carcinoma (RCC), head and neck cancer, and gastric
or gastroesophageal junction (GEJ) cancer will be presented.

“Research from our broad oncology clinical development program –
anchored by KEYTRUDA and including LYNPARZA and LENVIMA – continues to
support our goal of improving outcomes and providing clinically
meaningful results for patients and physicians,” said Dr. Roy Baynes,
senior vice president and head of global clinical development, chief
medical officer, Merck Research Laboratories. “At ASCO this year, we
look forward to presenting additional overall survival data for KEYTRUDA
across different tumor types, as well as first-time LYNPARZA data in
pancreatic cancer that reinforce our commitment to helping patients with
the most aggressive forms of cancer.”

Key abstracts to be presented at ASCO include:

• First presentation of data from the Phase 3 POLO trial evaluating the
  PARP inhibitor LYNPARZA as first-line maintenance treatment in
  patients with germline BRCA-mutated (gBRCAm) metastatic
  pancreatic cancer who did not progress on platinum-based chemotherapy
  (Abstract #LBA4). These results will be presented in the ASCO Plenary
  Session and highlighted in the ASCO press program. As previously
  announced in February 2019, the POLO trial met its primary endpoint of
  progression-free survival (PFS) compared to placebo.
• Five-year long-term OS data from the Phase 1b KEYNOTE-001 study
  evaluating KEYTRUDA in patients with advanced NSCLC (Abstract
  #LBA9015). These results will be highlighted in the ASCO press program.
• Updated data, including OS and progression-free survival 2 (PFS2)
  findings, from the Phase 3 KEYNOTE-189 trial evaluating KEYTRUDA in
  combination with pemetrexed (ALIMTA^®) and platinum
  chemotherapy in patients with metastatic nonsquamous NSCLC (Abstract
  #9013). The KEYNOTE-189 study was conducted in collaboration with Eli
  Lilly and Company, the makers of pemetrexed (ALIMTA^®).
• First presentation of data from the Phase 3 KEYNOTE-062 trial
  evaluating KEYTRUDA as first-line treatment (as monotherapy and in
  combination with chemotherapy) in patients with advanced gastric or
  gastroesophageal junction (GEJ) adenocarcinoma (Abstract #LBA4007). In
  April 2019, Merck announced KEYTRUDA met a primary endpoint as
  monotherapy, but not in combination with chemotherapy.
• Data, including OS, PFS and objective response rate (ORR), from new
  subgroup analyses of the combined International Metastatic RCC
  Database Consortium (IMDC) intermediate/poor risk and sarcomatoid
  subgroups in the Phase 3 KEYNOTE-426 trial evaluating KEYTRUDA in
  combination with axitinib compared to sunitinib as first-line therapy
  in patients with metastatic RCC (Abstract #4500).
• Results from the final analysis, including new OS data, from the Phase
  3 KEYNOTE-048 trial evaluating KEYTRUDA as first-line therapy (as
  monotherapy and in combination with chemotherapy) in patients with
  recurrent or metastatic head and neck squamous cell carcinoma
  (Abstract #6000).
• First presentation of data from the Phase 3 SOLO3 trial evaluating
  LYNPARZA in patients with relapsed BRCAm advanced ovarian
  cancer (Abstract #5506). As previously announced in December 2018, the
  SOLO3 trial met its primary endpoint of ORR with LYNPARZA compared to
  chemotherapy.
• First presentation of data from KEYNOTE-240 evaluating KEYTRUDA in
  previously treated patients with advanced hepatocellular carcinoma
  (HCC) (Abstract #4004). As previously announced in February 2019,
  KEYNOTE-240 did not meet its co-primary endpoints of OS and PFS
  compared with placebo plus best supportive care; there was an
  improvement in OS and results were directionally favorable for PFS in
  patients treated with KEYTRUDA compared with placebo, however these
  results did not meet statistical significance.

Details on Studies Listed Above, and Key Abstracts with Merck’s
Collaboration Partners

Cancer Type		Abstract Title		Presentation Details
KEYTRUDA (pembrolizumab)
Gastric or gastroesophageal junction		Pembrolizumab with or without chemotherapy versus chemotherapy for advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: The phase III KEYNOTE-062 Study		Abstract #LBA4007 (oral) J. Tabernero Sunday, June 2 11:57 a.m.-12:09 p.m. CT, Arie Crown Theater
Head and neck		Protocol-specified final analysis of the phase 3 KEYNOTE-048 trial of pembrolizumab (pembro) as first-line therapy for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC)		Abstract #6000 (oral) D. Rischin Friday, May 31 2:45-2:57 p.m. CT, E450
Liver		Results of KEYNOTE-240: phase 3 study of pembrolizumab (Pembro) vs best supportive care (BSC) for second line therapy in advanced hepatocellular carcinoma (HCC)		Abstract #4004 (oral) R. Finn Sunday, June 2 10:57-11:09 a.m. CT, Arie Crown Theater
Lung		Five-year long-term overall survival for patients with advanced NSCLC treated with pembrolizumab: Results from KEYNOTE-001		Abstract #LBA9015 (poster discussion) E. Garon Sunday, June 2 8:00-11:00 a.m. CT, Hall A (poster) 4:30-6:00 p.m. CT, Hall D1 (discussion)
		KEYNOTE-189: Updated OS and progression after the next line of therapy (PFS2) with pembrolizumab (pembro) plus chemo with pemetrexed and platinum vs placebo plus chemo for metastatic nonsquamous NSCLC		Abstract #9013 (poster discussion) S. Gadgeel Sunday, June 2 8:00-11:00 a.m. CT, Hall A (poster) 4:30-6:00 p.m. CT, Hall D1 (discussion)
Renal cell		Pembrolizumab (pembro) plus axitinib (axi) versus sunitinib as first-line therapy for metastatic renal cell carcinoma (mRCC): Outcomes in the combined IMDC intermediate/poor risk and sarcomatoid subgroups of the phase 3 KEYNOTE-426 study		Abstract #4500 (oral) B. Rini Monday, June 3 8:00-8:12 a.m. CT, Arie Crown Theater
LYNPARZA (olaparib) (in collaboration with AstraZeneca)
Ovarian		Olaparib monotherapy versus (vs) chemotherapy for germline BRCA-mutated (gBRCAm) platinum-sensitive relapsed ovarian cancer (PSR OC) patients (pts): Phase III SOLO3 trial		Abstract #5506 (oral) R. Penson Monday, June 3 3:15-3:27 p.m. CT, S406
		Olaparib maintenance therapy in patients (pts) with a BRCA1 and/or BRCA2 mutation (BRCAm) and newly diagnosed advanced ovarian cancer (OC): SOLO1 China cohort		Abstract #5554 (poster) L. Wu Saturday, June 1 1:15-4:15 p.m. CT, Hall A
Pancreatic		Olaparib as maintenance treatment following first-line platinum-based chemotherapy (PBC) in patients (pts) with a germline BRCA mutation and metastatic pancreatic cancer (mPC): Phase III POLO trial		Abstract #LBA4 (plenary) H. Kindler Sunday, June 2 3:15-3:30 p.m. CT, Hall B1
KEYTRUDA + LENVIMA (lenvatinib) (in collaboration with Eisai)
Endometrial		A phase 3 trial evaluating efficacy and safety of lenvatinib in combination with pembrolizumab in patients with advanced endometrial cancer		Abstract #TPS5607 (poster) V. Makker Saturday, June 1 1:15-4:15 p.m. CT, Hall A
Liver		Lenvatinib (len) plus pembrolizumab (pembro) for the first-line treatment of patients (pts) with advanced hepatocellular carcinoma (HCC): Phase 3 LEAP-002 study		Abstract #TPS4152 (poster) J. Llovet Monday, June 3 8:00-11:00 a.m. CT, Hall A
Lung		Randomized, double-blind, phase 3 trial of first-line pembrolizumab + platinum doublet chemotherapy (chemo) ± lenvatinib in patients (pts) with metastatic nonsquamous non-small-cell lung cancer (NSCLC): LEAP-006.		Abstract #TPS9118 (poster) R. Hui Sunday, June 2 8:00-11:00 a.m. CT, Hall A
Melanoma		Lenvatinib (len) plus pembrolizumab (pembro) in patients (pts) with advanced melanoma previously exposed to anti–PD-1/PD-L1 agents: Phase 2 LEAP-004 study		Abstract #TPS9594 (poster) A. Arance Fernandez Monday, June 3 1:15-4:15 p.m. CT, Hall A

For more information, including a complete list of abstract titles and
presentation dates and times for data from Merck’s oncology portfolio,
please visit the ASCO website at https://iplanner.asco.org/am2019/#/.

About KEYTRUDA

^®

(pembrolizumab) Injection,
100mg

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

Merck has the industry’s largest immuno-oncology clinical research
program. There are currently more than 1,000 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. The recommended dose of KEYTRUDA in patients with
unresectable or metastatic melanoma is 200 mg administered as an
intravenous infusion over 30 minutes every three weeks until disease
progression or unacceptable toxicity.

KEYTRUDA is indicated for the adjuvant treatment of patients with
melanoma with involvement of lymph node(s) following complete resection.
The recommended dose of KEYTRUDA for the adjuvant treatment of adult
patients with melanoma is 200 mg administered as an intravenous infusion
over 30 minutes every three weeks until disease recurrence, unacceptable
toxicity, or for up to 12 months in patients without disease recurrence.

Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is
indicated for the first-line treatment of patients with metastatic
nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK
genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or
paclitaxel protein-bound, is indicated for the first-line treatment of
patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment
of patients with stage III NSCLC who are not candidates for surgical
resection or definitive chemoradiation, or metastatic NSCLC, and whose
tumors express PD-L1 [tumor proportion score (TPS) ≥1%] as determined by
an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

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

In NSCLC, the recommended dose of KEYTRUDA is 200 mg administered as an
intravenous infusion over 30 minutes 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 the chemotherapy agents
administered in combination with KEYTRUDA, as appropriate.

Head and Neck Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or
metastatic head and neck squamous cell carcinoma (HNSCC) with disease
progression on or after platinum-containing chemotherapy. This
indication is approved under accelerated approval based on tumor
response rate and durability of response. Continued approval for this
indication may be contingent upon verification and description of
clinical benefit in the confirmatory trials. In HNSCC, KEYTRUDA 200 mg
is administered as an intravenous infusion over 30 minutes 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 3 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 200 mg is administered
as an intravenous infusion over 30 minutes 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 as an intravenous infusion over 30 minutes at a
dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until
disease progression or unacceptable toxicity, or up to 24 months in
patients without disease progression.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients
with refractory primary mediastinal large B-cell lymphoma (PMBCL), or
who have relapsed after 2 or more prior lines of therapy. This
indication is approved under accelerated approval based on tumor
response rate and durability of response. Continued approval for this
indication may be contingent upon verification and description of
clinical benefit in confirmatory trials. KEYTRUDA is not recommended for
the treatment of patients with PMBCL who require urgent cytoreductive
therapy. In adults with PMBCL, KEYTRUDA 200 mg is administered as an
intravenous infusion over 30 minutes every three weeks until disease
progression, unacceptable toxicity, or up to 24 months in patients
without disease progression. In pediatric patients with PMBCL, KEYTRUDA
is administered as an intravenous infusion over 30 minutes at a dose of
2 mg/kg (up to a maximum of 200 mg) every three weeks until disease
progression or unacceptable toxicity, or up to 24 months in patients
without disease progression.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally
advanced or metastatic urothelial carcinoma (mUC) who are not eligible
for cisplatin-containing chemotherapy and whose tumors express PD-L1
[combined positive score (CPS) ≥10] as determined by an FDA-approved
test, or in patients who are not eligible for any platinum-containing
chemotherapy regardless of PD-L1 status. This indication is approved
under accelerated approval based on tumor response rate and duration of
response. Continued approval for this indication may be contingent upon
verification and description of clinical benefit in the confirmatory
trials.

KEYTRUDA is indicated for the treatment of patients with locally
advanced or metastatic urothelial carcinoma (mUC) who have disease
progression during or following platinum-containing chemotherapy or
within 12 months of neoadjuvant or adjuvant treatment with
platinum-containing chemotherapy.

In locally advanced or metastatic urothelial carcinoma, KEYTRUDA 200 mg
is administered as an intravenous infusion over 30 minutes 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 200 mg is administered as
an intravenous infusion over 30 minutes 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 as an intravenous infusion over 30 minutes 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 (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 as an intravenous infusion over 30 minutes every
three weeks until disease progression, unacceptable toxicity, or up to
24 months in patients without disease progression.

Cervical Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or
metastatic cervical cancer with disease progression on or after
chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an
FDA-approved test. This indication is approved under accelerated
approval based on tumor response rate and durability of response.
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in the confirmatory
trials. The recommended dose of KEYTRUDA is 200 mg as an intravenous
infusion over 30 minutes every three weeks until disease progression,
unacceptable toxicity or up to 24 months in patients without disease
progression.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular
carcinoma (HCC) who have been previously treated with sorafenib. 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 as an intravenous infusion over 30 minutes every
three weeks until disease progression, unacceptable toxicity, or up to
24 months in patients without disease progression.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients
with recurrent locally advanced or metastatic Merkel cell carcinoma.
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 in adults is 200 mg administered as an intravenous infusion
over 30 minutes every three weeks until disease progression,
unacceptable toxicity, or up to 24 months in patients without disease
progression. The recommended dose of KEYTRUDA in pediatric patients is 2
mg/kg (up to a maximum of 200 mg), administered as an intravenous
infusion over 30 minutes every three weeks until disease progression or
unacceptable toxicity, or up to 24 months in patients without disease
progression.

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line
treatment of patients with advanced renal cell carcinoma. In renal cell
carcinoma, KEYTRUDA 200 mg is administered as an intravenous infusion
over 30 minutes every 3 weeks in combination with 5 mg axitinib orally
twice daily until disease progression, unacceptable toxicity, or for
KEYTRUDA, up to 24 months in patients without disease progression. When
axitinib is used in combination with KEYTRUDA, dose escalation of
axitinib above the initial 5 mg dose may be considered at intervals of
six weeks or longer. See also the Prescribing Information for
recommended axitinib dosing information.

Selected Important Safety Information for KEYTRUDA (pembrolizumab)
Injection, 100mg

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases.
Pneumonitis occurred in 3.4% (94/2799) of patients with various cancers
receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4
(0.3%), and 5 (0.1%). Pneumonitis occurred in 8.2% (65/790) of NSCLC
patients receiving KEYTRUDA as a single agent, including Grades 3-4 in
3.2% of patients, and occurred more frequently in patients with a
history of prior thoracic radiation (17%) compared to those without
(7.7%).

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.

Immune-Mediated Colitis

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

Immune-Mediated Hepatitis, or Hepatoxicity (in Combination With
Axitinib)

Immune-Mediated Hepatitis

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

Hepatotoxicity (in Combination With Axitinib)

KEYTRUDA in combination with axitinib can cause hepatic toxicity with
higher than expected frequencies of Grades 3 and 4 ALT and AST
elevations compared to KEYTRUDA alone. Grades 3 and 4 increased ALT and
AST were seen in 20% and 13% of patients, respectively. Monitor liver
enzymes before initiation of and periodically throughout treatment.
Consider more frequent monitoring of liver enzymes as compared to when
the drugs are used in monotherapy. For elevated liver enzymes, interrupt
KEYTRUDA and axitinib, and consider administering corticosteroids as
needed.

Immune-Mediated Endocrinopathies

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

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

Immune-Mediated Nephritis and Renal Dysfunction

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

Immune-Mediated Skin Reactions

Immune-mediated rashes, including Stevens-Johnson syndrome (SJS), toxic
epidermal necrolysis (TEN) (some cases with fatal outcome), exfoliative
dermatitis, and bullous pemphigoid, can occur. Monitor patients for
suspected severe skin reactions and based on the severity of the adverse
reaction, withhold or permanently discontinue KEYTRUDA and administer
corticosteroids. For signs or symptoms of SJS or TEN, withhold KEYTRUDA
and refer the patient for specialized care for assessment and treatment.
If SJS or TEN is confirmed, permanently discontinue KEYTRUDA.

Other Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions, which may be severe or fatal, can
occur in any organ system or tissue in patients receiving KEYTRUDA and
may also occur after discontinuation of treatment. For suspected
immune-mediated adverse reactions, ensure adequate evaluation to confirm
etiology or exclude other causes. Based on the severity of the adverse
reaction, withhold KEYTRUDA and administer corticosteroids. Upon
improvement to Grade 1 or less, initiate corticosteroid taper and
continue to taper over at least 1 month. Based on limited data from
clinical studies in patients whose immune-related adverse reactions
could not be controlled with corticosteroid use, administration of other
systemic immunosuppressants can be considered. Resume KEYTRUDA when the
adverse reaction remains at Grade 1 or less following corticosteroid
taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated
adverse reaction that recurs and for any life-threatening
immune-mediated adverse reaction.

The following clinically significant immune-mediated adverse reactions
occurred in less than 1% (unless otherwise indicated) of 2799 patients:
arthritis (1.5%), uveitis, myositis, Guillain-Barré syndrome, myasthenia
gravis, vasculitis, pancreatitis, hemolytic anemia, sarcoidosis, and
encephalitis. In addition, myelitis and myocarditis were reported in
other clinical trials, including cHL, and postmarketing use.

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

Infusion-Related Reactions

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

Complications of Allogeneic Hematopoietic Stem Cell Transplantation
(HSCT)

Immune-mediated complications, including fatal events, occurred in
patients who underwent allogeneic HSCT after treatment with KEYTRUDA. Of
23 patients with cHL who proceeded to allogeneic HSCT after KEYTRUDA, 6
(26%) developed graft-versus-host disease (GVHD) (1 fatal case) and 2
(9%) developed severe hepatic veno-occlusive disease (VOD) after
reduced-intensity conditioning (1 fatal case). Cases of fatal hyperacute
GVHD after allogeneic HSCT have also been reported in patients with
lymphoma who received a PD-1 receptor–blocking antibody before
transplantation. Follow patients closely for early evidence of
transplant-related complications such as hyperacute graft-versus-host
disease (GVHD), Grade 3 to 4 acute GVHD, steroid-requiring febrile
syndrome, hepatic veno-occlusive disease (VOD), and other
immune-mediated adverse reactions.

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

Increased Mortality in Patients With Multiple Myeloma

In 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
trials.

Embryofetal Toxicity

Based on its mechanism of action, KEYTRUDA can cause fetal harm when
administered to a pregnant woman. Advise women of this potential risk.
In females of reproductive potential, verify pregnancy status prior to
initiating KEYTRUDA and advise them to use effective contraception
during treatment and for 4 months after the last dose.

Adverse Reactions

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9%
of 555 patients with advanced melanoma; adverse reactions leading to
permanent discontinuation in more than one patient were colitis (1.4%),
autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy
(0.4%), and cardiac failure (0.4%). The most common adverse reactions
(≥20%) with KEYTRUDA were fatigue (28%), diarrhea (26%), rash (24%), and
nausea (21%).

In KEYNOTE-054, KEYTRUDA was permanently discontinued due to adverse
reactions in 14% of 509 patients; the most common (≥1%) were pneumonitis
(1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse reactions
occurred in 25% of patients receiving KEYTRUDA. The most common adverse
reaction (≥20%) with KEYTRUDA was diarrhea (28%).

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

In KEYNOTE-407, when KEYTRUDA was administered with carboplatin and
either paclitaxel or paclitaxel protein-bound in metastatic squamous
NSCLC, KEYTRUDA was discontinued due to adverse reactions in 15% of 101
patients. The most frequent serious adverse reactions reported in at
least 2% of patients were febrile neutropenia, pneumonia, and urinary
tract infection. Adverse reactions observed in KEYNOTE-407 were similar
to those observed in KEYNOTE-189 with the exception that increased
incidences of alopecia (47% vs 36%) and peripheral neuropathy (31% vs
25%) were observed in the KEYTRUDA and chemotherapy arm compared to the
placebo and chemotherapy arm in KEYNOTE-407.

In KEYNOTE-042, KEYTRUDA was discontinued due to adverse reactions in
19% of 636 patients; the most common were pneumonitis (3%), death due to
unknown cause (1.6%), and pneumonia (1.4%). The most frequent serious
adverse reactions reported in at least 2% of patients were pneumonia
(7%), pneumonitis (3.9%), pulmonary embolism (2.4%), and pleural
effusion (2.2%). The most common adverse reaction (≥20%) was fatigue
(25%).

In KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to adverse
reactions in 8% of 682 patients with metastatic NSCLC; the most common
was pneumonitis (1.8%). The most common adverse reactions (≥20%) were
decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%).

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

In KEYNOTE-087, KEYTRUDA was discontinued due to adverse reactions in 5%
of 210 patients with cHL. Serious adverse reactions occurred in 16% of
patients; those ≥1% included pneumonia, pneumonitis, pyrexia, dyspnea,
GVHD, and herpes zoster. Two patients died from causes other than
disease progression; 1 from GVHD after subsequent allogeneic HSCT and 1
from septic shock. The most common adverse reactions (≥20%) were fatigue
(26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea
(20%), and rash (20%).

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

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

In KEYNOTE-045, KEYTRUDA was discontinued due to adverse reactions in 8%
of 266 patients with locally advanced or metastatic urothelial
carcinoma. The most common adverse reaction resulting in permanent
discontinuation of KEYTRUDA was pneumonitis (1.9%). Serious adverse
reactions occurred in 39% of KEYTRUDA-treated patients; those ≥2% were
urinary tract infection, pneumonia, anemia, and pneumonitis. The most
common adverse reactions (≥20%) in patients who received KEYTRUDA were
fatigue (38%), musculoskeletal pain (32%), pruritus (23%), decreased
appetite (21%), nausea (21%), and rash (20%).

Adverse reactions occurring in patients with gastric cancer were similar
to those occurring in patients with melanoma or NSCLC who received
KEYTRUDA as a monotherapy.

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

Adverse reactions occurring in patients with HCC were generally similar
to those in patients with melanoma or NSCLC who received KEYTRUDA as a
monotherapy, with the exception of increased incidences of ascites (8%
Grades 3-4) and immune-mediated hepatitis (2.9%). Laboratory
abnormalities (Grades 3-4) that occurred at a higher incidence were
elevated AST (20%), ALT (9%), and hyperbilirubinemia (10%).

Among the 50 patients with MCC enrolled in study KEYNOTE-017, adverse
reactions occurring in patients with MCC were generally similar to those
occurring in patients with melanoma or NSCLC who received KEYTRUDA as a
monotherapy. Laboratory abnormalities (Grades 3-4) that occurred at a
higher incidence were elevated AST (11%) and hyperglycemia (19%).

In KEYNOTE-426, when KEYTRUDA was administered in combination with
axitinib, fatal adverse reactions occurred in 3.3% of 429 patients.
Serious adverse reactions occurred in 40% of patients, the most frequent
of which (≥1%) included hepatotoxicity (7%), diarrhea (4.2%), acute
kidney injury (2.3%), dehydration (1%), and pneumonitis (1%). Permanent
discontinuation due to an adverse reaction occurred in 31% of patients;
KEYTRUDA only (13%), axitinib only (13%), and the combination (8%). The
most common adverse reactions (>1%) resulting in permanent
discontinuation of KEYTRUDA, axitinib or the combination were
hepatotoxicity (13%), diarrhea/colitis (1.9%), acute kidney injury
(1.6%), and cerebrovascular accident (1.2%). When KEYTRUDA was used in
combination with axitinib, the most common adverse reactions (≥20%) were
diarrhea (56%), fatigue/asthenia (52%), hypertension (48%),
hepatotoxicity (39%), hypothyroidism (35%), decreased appetite (30%),
palmar-plantar erythrodysesthesia (28%), nausea (28%),
stomatitis/mucosal inflammation (27%), dysphonia (25%), rash (25%),
cough (21%), and constipation (21%).

Lactation

Because of the potential for serious adverse reactions in breastfed
children, advise women not to breastfeed during treatment and for 4
months after the final dose.

Pediatric Use

There is limited experience in pediatric patients. In a trial, 40
pediatric patients (16 children aged 2 years to younger than 12 years
and 24 adolescents aged 12 years to 18 years) with various cancers,
including unapproved usages, 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 2 doses or more. The safety
profile in these pediatric patients was similar to that seen in adults;
adverse reactions 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%), increased
transaminases (28%), and hyponatremia (18%).

About LYNPARZA

^®

(olaparib)

LYNPARZA is a first-in-class 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. Inhibition of PARP with LYNPARZA leads to the trapping of
PARP bound to DNA single-strand breaks, stalling of replication forks,
their collapse and the generation of DNA double-strand breaks and cancer
cell death. LYNPARZA is being tested in a range of tumor types with
defects and dependencies in the DDR.

LYNPARZA, which is being jointly developed and commercialized by
AstraZeneca and Merck, has a broad and advanced clinical trial
development program, and AstraZeneca and Merck are working together to
understand how it may affect multiple PARP-dependent tumors as a
monotherapy and in combination across multiple cancer types.

LYNPARZA

^®

Indications

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

First-Line Maintenance BRCAm Advanced Ovarian Cancer

For the maintenance treatment of adult patients with deleterious or
suspected deleterious germline or somatic BRCA-mutated (gBRCAm
or sBRCAm) advanced epithelial ovarian, fallopian tube or
primary peritoneal cancer who are in complete or partial response to
first-line platinum-based chemotherapy. Select patients with gBRCAm
advanced epithelial ovarian, fallopian tube or primary peritoneal cancer
for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Maintenance Recurrent Ovarian Cancer

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.

Advanced gBRCAm ovarian cancer

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.

gBRCAm, HER2-negative metastatic breast cancer

In patients with deleterious or suspected deleterious gBRCAm, human
epidermal growth factor receptor 2 (HER2)-negative metastatic breast
cancer who have 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 therapy.
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, 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.

Females

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.

Males

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—First-Line Maintenance BRCAm Advanced
Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of patients in
clinical trials of LYNPARZA in the first-line maintenance setting
for SOLO-1 were: nausea (77%), fatigue (67%), abdominal pain
(45%), vomiting (40%), anemia (38%), diarrhea (37%), constipation (28%),
upper respiratory tract infection/influenza/ nasopharyngitis/bronchitis
(28%), dysgeusia (26%), decreased appetite (20%), dizziness (20%),
neutropenia (17%), dyspepsia (17%), dyspnea (15%), leukopenia (13%), UTI
(13%), thrombocytopenia (11%), and stomatitis (11%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in
clinical trials of LYNPARZA in the first-line maintenance setting for
SOLO-1 were: decrease in hemoglobin (87%), increase in mean
corpuscular volume (87%), decrease in leukocytes (70%), decrease in
lymphocytes (67%), decrease in absolute neutrophil count (51%), decrease
in platelets (35%), and increase in serum creatinine (34%).

ADVERSE REACTIONS—Maintenance Recurrent Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients in
clinical trials of LYNPARZA in the maintenance setting for SOLO-2
were: 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%), decreased appetite
(21%), and dyspepsia (20%).

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/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 (pooled
from 6 studies) were: decrease in hemoglobin (90%), mean corpuscular
volume elevation (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 metastatic 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. 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 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 or moderate hepatic impairment
(Child-Pugh classification A and B). There are no data in patients with
severe hepatic impairment (Child-Pugh classification C).

Renal Impairment: No adjustment to the starting dose is necessary
in patients with mild renal impairment (CLcr=51-80 mL/min) but patients
should be monitored closely for toxicity. 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).

About LENVIMA

^®

(lenvatinib) capsules 10 mg
and 4 mg

LENVIMA^® (lenvatinib) is a kinase inhibitor that is indicated
in the U.S.:

• For the treatment of patients with locally recurrent or metastatic,
  progressive radioactive iodine-refractory differentiated thyroid
  cancer (DTC)
• In combination with everolimus, for the treatment of patients with
  advanced renal cell carcinoma (RCC) following one prior
  anti-angiogenic therapy
• For the first-line treatment of patients with unresectable
  hepatocellular carcinoma (HCC)

LENVIMA, discovered and developed by Eisai, is a kinase inhibitor that
inhibits the kinase activities of vascular endothelial growth factor
(VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). LENVIMA
inhibits other kinases that have been implicated in pathogenic
angiogenesis, tumor growth, and cancer progression in addition to their
normal cellular functions, including fibroblast growth factor (FGF)
receptors FGFR1-4; the platelet derived growth factor receptor alpha
(PDGFRα), KIT, and RET. The combination of lenvatinib and everolimus
showed increased anti-angiogenic and anti-tumor activity as demonstrated
by decreased human endothelial cell proliferation, tube formation, and
VEGF signaling in vitro and tumor volume in mouse xenograft
models of human renal cell cancer greater than each drug alone.
Lenvatinib also exhibited antiproliferative activity in hepatocellular
carcinoma cell lines dependent on activated FGFR signaling with a
concurrent inhibition of FGF-receptor substrate 2α (FRS2α)
phosphorylation.

Important Safety Information for LENVIMA

Warnings and Precautions

Hypertension. In DTC, hypertension occurred in 73% of patients on
LENVIMA (44% grade 3-4). In RCC, hypertension occurred in 42% of
patients on LENVIMA + everolimus (13% grade 3). Systolic blood pressure
≥160 mmHg occurred in 29% of patients, and 21% had diastolic blood
pressure ≥100 mmHg. In HCC, hypertension occurred in 45% of
LENVIMA-treated patients (24% grade 3). Grade 4 hypertension was not
reported in HCC.

Serious complications of poorly controlled hypertension have been
reported. Control blood pressure prior to initiation. Monitor blood
pressure after 1 week, then every 2 weeks for the first 2 months, and
then at least monthly thereafter during treatment. Withhold and resume
at reduced dose when hypertension is controlled or permanently
discontinue based on severity.

Cardiac Dysfunction. Serious and fatal cardiac dysfunction can
occur with LENVIMA. Across clinical trials in 799 patients with DTC,
RCC, and HCC, grade 3 or higher cardiac dysfunction occurred in 3% of
LENVIMA-treated patients. Monitor for clinical symptoms or signs of
cardiac dysfunction. Withhold and resume at reduced dose upon recovery
or permanently discontinue based on severity.

Arterial Thromboembolic Events. Among patients receiving LENVIMA
or LENVIMA + everolimus, arterial thromboembolic events of any severity
occurred in 2% of patients in RCC and HCC and 5% in DTC. Grade 3-5
arterial thromboembolic events ranged from 2% to 3% across all clinical
trials.

Permanently discontinue following an arterial thrombotic event. The
safety of resuming after an arterial thromboembolic event has not been
established and LENVIMA has not been studied in patients who have had an
arterial thromboembolic event within the previous 6 months.

Hepatotoxicity. Across clinical studies enrolling 1,327
LENVIMA-treated patients with malignancies other than HCC, serious
hepatic adverse reactions occurred in 1.4% of patients. Fatal events,
including hepatic failure, acute hepatitis and hepatorenal syndrome,
occurred in 0.5% of patients. In HCC, hepatic encephalopathy occurred in
8% of LENVIMA-treated patients (5% grade 3-5). Grade 3-5 hepatic failure
occurred in 3% of LENVIMA-treated patients. 2% of patients discontinued
LENVIMA due to hepatic encephalopathy and 1% discontinued due to hepatic
failure.

Monitor liver function prior to initiation, then every 2 weeks for the
first 2 months, and at least monthly thereafter during treatment.
Monitor patients with HCC closely for signs of hepatic failure,
including hepatic encephalopathy. Withhold and resume at reduced dose
upon recovery or permanently discontinue based on severity.

Renal Failure or Impairment. Serious including fatal renal
failure or impairment can occur with LENVIMA. Renal impairment was
reported in 14% and 7% of LENVIMA-treated patients in DTC and HCC,
respectively. Grade 3-5 renal failure or impairment occurred in 3% of
patients with DTC and 2% of patients with HCC, including 1 fatal event
in each study. In RCC, renal impairment or renal failure was reported in
18% of LENVIMA + everolimus–treated patients (10% grade 3).

Initiate prompt management of diarrhea or dehydration/hypovolemia.
Withhold and resume at reduced dose upon recovery or permanently
discontinue for renal failure or impairment based on severity.

Proteinuria. In DTC and HCC, proteinuria was reported in 34% and
26% of LENVIMA-treated patients, respectively. Grade 3 proteinuria
occurred in 11% and 6% in DTC and HCC, respectively. In RCC, proteinuria
occurred in 31% of patients receiving LENVIMA + everolimus (8% grade 3).

Monitor for proteinuria prior to initiation and periodically during
treatment. If urine dipstick proteinuria ≥2+ is detected, obtain a
24-hour urine protein. Withhold and resume at reduced dose upon recovery
or permanently discontinue based on severity.

Diarrhea. Of the 737 LENVIMA-treated patients in DTC and HCC,
diarrhea occurred in 49% (6% grade 3). In RCC, diarrhea occurred in 81%
of LENVIMA + everolimus–treated patients (19% grade 3). Diarrhea was the
most frequent cause of dose interruption/reduction, and diarrhea
recurred despite dose reduction.

Promptly initiate management of diarrhea. Withhold and resume at reduced
dose upon recovery or permanently discontinue based on severity.

Fistula Formation and Gastrointestinal Perforation. Of the 799
patients treated with LENVIMA or LENVIMA + everolimus in DTC, RCC, and
HCC, fistula or gastrointestinal perforation occurred in 2%. Fistulas
and gastrointestinal perforations have also been reported in other
lenvatinib clinical trials and in post-marketing experience.
Pneumothorax has been reported with and without clear evidence of a
bronchopleural fistula. Some reports of gastrointestinal perforation,
fistula, and pneumothorax occurred in association with tumor regression
or necrosis. In most cases of fistula formation or gastrointestinal
perforation, risk factors such as prior surgery or radiotherapy were
present.

Permanently discontinue in patients who develop gastrointestinal
perforation of any severity or grade 3-4 fistula.

QT Interval Prolongation. In DTC, QT/QTc interval prolongation
occurred in 9% of LENVIMA-treated patients and QT interval prolongation
of >500 ms occurred in 2%. In RCC, QTc interval increases of >60 ms
occurred in 11% of patients receiving LENVIMA + everolimus and QTc
interval >500 ms occurred in 6%. In HCC, QTc interval increases of >60
ms occurred in 8% of LENVIMA-treated patients and QTc interval >500 ms
occurred in 2%.

Monitor and correct electrolyte abnormalities at baseline and
periodically during treatment. Monitor electrocardiograms in patients
with congenital long QT syndrome, congestive heart failure,
bradyarrhythmias, or those who are taking drugs known to prolong the QT
interval, including Class Ia and III antiarrhythmics. Withhold and
resume at reduced dose upon recovery based on severity.

Hypocalcemia. In DTC, grade 3-4 hypocalcemia occurred in 9% of
LENVIMA-treated patients. In 65% of cases, hypocalcemia improved or
resolved following calcium supplementation with or without dose
interruption or dose reduction. In RCC, grade 3-4 hypocalcemia occurred
in 6% of LENVIMA + everolimus–treated patients. In HCC, grade 3
hypocalcemia occurred in 0.8% of LENVIMA-treated patients.

Monitor blood calcium levels at least monthly and replace calcium as
necessary during treatment. Withhold and resume at reduced dose upon
recovery or permanently discontinue depending on severity.

Reversible Posterior Leukoencephalopathy Syndrome. Across
clinical studies of 1,823 patients who received LENVIMA as a single
agent, RPLS occurred in 0.3%. Confirm diagnosis of RPLS with MRI.
Withhold and resume at reduced dose upon recovery or permanently
discontinue depending on severity and persistence of neurologic symptoms.

Hemorrhagic Events. Serious including fatal hemorrhagic events
can occur with LENVIMA. In DTC, RCC, and HCC clinical trials,
hemorrhagic events, of any grade, occurred in 29% of the 799 patients
treated with LENVIMA as a single agent or in combination with
everolimus. The most frequently reported hemorrhagic events (all grades
and occurring in at least 5% of patients) were epistaxis and hematuria.
In DTC, grade 3-5 hemorrhage occurred in 2% of LENVIMA-treated patients,
including 1 fatal intracranial hemorrhage among 16 patients who received
LENVIMA and had CNS metastases at baseline. In RCC, grade 3-5 hemorrhage
occurred in 8% of LENVIMA + everolimus–treated patients, including 1
fatal cerebral hemorrhage. In HCC, grade 3-5 hemorrhage occurred in 5%
of LENVIMA-treated patients, including 7 fatal hemorrhagic events.

Serious tumor-related bleeds, including fatal hemorrhagic events,
occurred in LENVIMA-treated patients in clinical trials and in the
postmarketing setting. In postmarketing surveillance, serious and fatal
carotid artery hemorrhages were seen more frequently in patients with
anaplastic thyroid carcinoma (ATC) than other tumors. Safety and
effectiveness of LENVIMA in patients with ATC have not been demonstrated
in clinical trials.

Consider the risk of severe or fatal hemorrhage associated with tumor
invasion or infiltration of major blood vessels (eg, carotid artery).
Withhold and resume at reduced dose upon recovery or permanently
discontinue based on severity.

Impairment of Thyroid Stimulating Hormone Suppression/Thyroid
Dysfunction. LENVIMA impairs exogenous thyroid suppression. In DTC,
88% of patients had baseline thyroid stimulating hormone (TSH) level
≤0.5 mU/L. In patients with normal TSH at baseline, elevation of TSH
level >0.5 mU/L was observed post baseline in 57% of LENVIMA-treated
patients. In RCC and HCC, grade 1 or 2 hypothyroidism occurred in 24% of
LENVIMA + everolimus–treated patients and 21% of LENVIMA-treated
patients, respectively. In patients with normal or low TSH at baseline,
elevation of TSH was observed post baseline in 70% of LENVIMA-treated
patients in HCC and 60% of LENVIMA + everolimus–treated patients in RCC.

Monitor thyroid function prior to initiation and at least monthly during
treatment. Treat hypothyroidism according to standard medical practice.

Wound Healing Complications. Wound healing complications,
including fistula formation and wound dehiscence, can occur with
LENVIMA. Withhold for at least 6 days prior to scheduled surgery. Resume
after surgery based on clinical judgment of adequate wound healing.
Permanently discontinue in patients with wound healing complications.

Embryo-fetal Toxicity. Based on its mechanism of action and data
from animal reproduction studies, LENVIMA can cause fetal harm when
administered to pregnant women. In animal reproduction studies, oral
administration of lenvatinib during organogenesis at doses below the
recommended clinical doses resulted in embryotoxicity, fetotoxicity, and
teratogenicity in rats and rabbits. Advise pregnant women of the
potential risk to a fetus; and advise females of reproductive potential
to use effective contraception during treatment with LENVIMA and for at
least 30 days after the last dose.

Adverse Reactions

In DTC, the most common adverse reactions (≥30%) observed in
LENVIMA-treated patients were hypertension (73%), fatigue (67%),
diarrhea (67%), arthralgia/myalgia (62%), decreased appetite (54%),
decreased weight (51%), nausea (47%), stomatitis (41%), headache (38%),
vomiting (36%), proteinuria (34%), palmar-plantar erythrodysesthesia
syndrome (32%), abdominal pain (31%), and dysphonia (31%). The most
common serious adverse reactions (≥2%) were pneumonia (4%), hypertension
(3%), and dehydration (3%). Adverse reactions led to dose reductions in
68% of LENVIMA-treated patients; 18% discontinued LENVIMA. The most
common adverse reactions (≥10%) resulting in dose reductions were
hypertension (13%), proteinuria (11%), decreased appetite (10%), and
diarrhea (10%); the most common adverse reactions (≥1%) resulting in
discontinuation of LENVIMA were hypertension (1%) and asthenia (1%).

In RCC, the most common adverse reactions (≥30%) observed in LENVIMA +
everolimus–treated patients were diarrhea (81%), fatigue (73%),
arthralgia/myalgia (55%), decreased appetite (53%), vomiting (48%),
nausea (45%), stomatitis (44%), hypertension (42%), peripheral edema
(42%), cough (37%), abdominal pain (37%), dyspnea (35%), rash (35%),
decreased weight (34%), hemorrhagic events (32%), and proteinuria (31%).
The most common serious adverse reactions (≥5%) were renal failure
(11%), dehydration (10%), anemia (6%), thrombocytopenia (5%), diarrhea
(5%), vomiting (5%), and dyspnea (5%). Adverse reactions led to dose
reductions or interruption in 89% of patients. The most common adverse
reactions (≥5%) resulting in dose reductions were diarrhea (21%),
fatigue (8%), thrombocytopenia (6%), vomiting (6%), nausea (5%), and
proteinuria (5%). Treatment discontinuation due to an adverse reaction
occurred in 29% of patients.

In HCC, the most common adverse reactions (≥20%) observed in
LENVIMA-treated patients were hypertension (45%), fatigue (44%),
diarrhea (39%), decreased appetite (34%), arthralgia/myalgia (31%),
decreased weight (31%), abdominal pain (30%), palmar-plantar
erythrodysesthesia syndrome (27%), proteinuria (26%), dysphonia (24%),
hemorrhagic events (23%), hypothyroidism (21%), and nausea (20%). The
most common serious adverse reactions (≥2%) were hepatic encephalopathy
(5%), hepatic failure (3%), ascites (3%), and decreased appetite (2%).
Adverse reactions led to dose reductions or interruption in 62% of
patients. The most common adverse reactions (≥5%) resulting in dose
reductions were fatigue (9%), decreased appetite (8%), diarrhea (8%),
proteinuria (7%), hypertension (6%), and palmar-plantar
erythrodysesthesia syndrome (5%). Treatment discontinuation due to an
adverse reaction occurred in 20% of patients. The most common adverse
reactions (≥1%) resulting in discontinuation of LENVIMA were fatigue
(1%), hepatic encephalopathy (2%), hyperbilirubinemia (1%), and hepatic
failure (1%).

Use in Specific Populations

Because of the potential for serious adverse reactions in breastfed
infants, advise women to discontinue breastfeeding during treatment and
for at least 1 week after last dose. LENVIMA may impair fertility in
males and females of reproductive potential.

No dose adjustment is recommended for patients with mild (CLcr 60-89
mL/min) or moderate (CLcr 30-59 mL/min) renal impairment. LENVIMA
concentrations may increase in patients with DTC or RCC and severe (CLcr
15-29 mL/min) renal impairment. Reduce the dose for patients with RCC or
DTC and severe renal impairment. There is no recommended dose for
patients with HCC and severe renal impairment. LENVIMA has not been
studied in patients with end stage renal disease.

No dose adjustment is recommended for patients with HCC and mild hepatic
impairment (Child-Pugh A). There is no recommended dose for patients
with HCC with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic
impairment.

No dose adjustment is recommended for patients with DTC or RCC and mild
or moderate hepatic impairment. LENVIMA concentrations may increase in
patients with DTC or RCC and severe hepatic impairment. Reduce the dose
for patients with DTC or RCC and severe hepatic impairment.

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. Working together, the companies will develop
LYNPARZA and selumetinib in combination with other potential new
medicines and as monotherapies. Independently, the companies will
develop LYNPARZA and selumetinib in combination with their respective
PD-L1 and PD-1 medicines.

About the Eisai and Merck Strategic Collaboration

In March 2018, Eisai and Merck, known as MSD outside the United States
and Canada, through an affiliate, entered into a strategic collaboration
for the worldwide co-development and co-commercialization of LENVIMA.
Under the agreement, the companies will jointly develop, manufacture and
commercialize LENVIMA, both as monotherapy and in combination with
Merck’s anti-PD-1 therapy KEYTRUDA.

In addition to ongoing clinical studies evaluating the LENVIMA and
KEYTRUDA combination across several different tumor types, including
renal cell carcinoma, the companies will jointly initiate new clinical
studies through the LEAP (LEnvatinib And Pembrolizumab) clinical
program, which will evaluate the combination to support 11 potential
indications in six types of cancer (endometrial cancer, hepatocellular
carcinoma, melanoma, non-small cell lung cancer, squamous cell carcinoma
of the head and neck, and urothelial cancer). The LEAP clinical program
also includes a new basket trial targeting six additional cancer types
(biliary tract cancer, breast cancer, colorectal cancer, gastric cancer,
glioblastoma and ovarian cancer). The LENVIMA and KEYTRUDA combination
is not approved in any cancer types today.

Merck’s Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology
medicines to help people with cancer worldwide. At Merck, the potential
to bring new hope to people with cancer drives our purpose and
supporting accessibility to our cancer medicines is our commitment. As
part of our focus on cancer, Merck is committed to exploring the
potential of immuno-oncology with one of the largest development
programs in the industry across more than 30 tumor types. We also
continue to strengthen our portfolio through strategic acquisitions and
are prioritizing the development of several promising oncology
candidates with the potential to improve the treatment of advanced
cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

About Merck

For more than a century, Merck, a leading global biopharmaceutical
company known as MSD outside of the United States and Canada, has been
inventing for life, bringing forward medicines and vaccines for many of
the world’s most challenging diseases. Through our prescription
medicines, vaccines, biologic therapies and animal health products, we
work with customers and operate in more than 140 countries to deliver
innovative health solutions. We also demonstrate our commitment to
increasing access to health care through far-reaching policies, programs
and partnerships. Today, Merck continues to be at the forefront of
research to advance the prevention and treatment of diseases that
threaten people and communities around the world – including cancer,
cardio-metabolic diseases, emerging animal diseases, Alzheimer’s disease
and infectious diseases including HIV and Ebola. For more information,
visit www.merck.com and connect
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 2018 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
Medication Guide for KEYTRUDA (pembrolizumab) at 

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

.

Please see complete Prescribing Information for LYNPARZA (olaparib)
tablets at

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

 and
complete Prescribing Information for LYNPARZA capsules, at

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

 including
Patient Information (Medication Guides).

Please see Prescribing Information for LENVIMA (lenvatinib) at

http://www.lenvima.com/pdfs/prescribing-information.pdf

.

LENVIMA^® is a registered trademark used by Eisai Inc. under
license from Eisai R&D Management Co., Ltd.

Media Contacts:
Pamela Eisele
(267) 305-3558

Kristen Drake
(908) 740-1679

Investor Contacts:
Teri Loxam
(908) 740-1986

Michael DeCarbo
(908) 740-1807