Merck Highlights Breadth of Immuno-Oncology Research Program in Genitourinary Cancers at ASCO GU

First-Time Data from Pivotal Phase 3 KEYNOTE-426 Trial Showing
KEYTRUDA
® (pembrolizumab) in Combination with
Inlyta
® (axitinib) Significantly Improved OS,
PFS and ORR Compared to Sunitinib Monotherapy in First-Line Treatment of
Advanced Renal Cell Carcinoma

Three New KEYTRUDA Combination Datasets from the Largest Study of
Anti-PD-1 Therapy in Metastatic Prostate Cancer (KEYNOTE-365)

KENILWORTH, N.J.–(BUSINESS WIRE)–lt;a href=”https://twitter.com/search?q=%24MRK&src=ctag” target=”_blank”gt;$MRKlt;/agt; lt;a href=”https://twitter.com/hashtag/MRK?src=hash” target=”_blank”gt;#MRKlt;/agt;–Merck (NYSE: MRK), known as MSD outside the United States and Canada,
today announced that new combination and monotherapy data from the
company’s broad immuno-oncology research program in genitourinary
cancers – renal, prostate and bladder − will be presented at the 2019
Genitourinary Cancers Symposium (ASCO GU) in San Francisco from February
14-16. Survival data from the pivotal Phase 3 KEYNOTE-426 trial with
KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with Inlyta
(axitinib), a tyrosine kinase inhibitor, for the first-line treatment of
advanced or metastatic renal cell carcinoma (RCC) will be presented for
the first-time (Abstract #543). In October 2018, Merck announced that
KEYNOTE-426 met both primary endpoints of overall survival (OS) and
progression-free survival (PFS), and the key secondary endpoint of
objective response rate (ORR). Data released today from the first
interim analysis showed KEYTRUDA in combination with axitinib, when
compared to sunitinib, significantly improved OS, reducing the risk of
death by nearly half, (HR 0.53 [95% CI 0.38-0.74]; P=0.0001), as well as
PFS (HR 0.69 [95% CI 0.57-0.84]; P=0.0001) and ORR (59.3% vs. 35.7%;
P=0.0001). Results across OS, PFS and ORR were consistent across all
IMDC risk groups and regardless of PD-L1 expression. Treatment-related
adverse events were grade 3-5 in 62.9 percent of patients in the
KEYTRUDA and axitinib arm vs 58.1 percent in the sunitinib arm and led
to regimen discontinuation in 6.3 percent vs 10.1 percent of patients in
those arms, respectively. Full results from KEYNOTE-426 will be
presented at the meeting.

Merck is pursuing a broad clinical program in advanced cancers of the
kidney, prostate and bladder with the goal of advancing new treatment
options for patients afflicted by historically difficult to treat
malignancies,” said Dr. Roger M. Perlmutter, president, Merck Research
Laboratories. “The improvement in survival achieved with KEYTRUDA in
combination with axitinib for the first-line treatment of advanced renal
cell carcinoma, which will be described in detail at the ASCO GU
meeting, underscores this commitment.”

More than 20 abstracts across Merck’s oncology portfolio – across RCC,
prostate cancer, non-muscle invasive bladder cancer (NMIBC) and
urothelial carcinoma – have been accepted for presentation. Select data
highlights at ASCO GU include:

Renal Cell Carcinoma

  • Abstract #543 Oral Presentation: Pembrolizumab (pembro) plus axitinib
    (axi) versus sunitinib as first-line therapy for locally advanced or
    metastatic renal cell carcinoma (mRCC): phase III KEYNOTE-426 study.
    T. Powles. Saturday, Feb. 16. 2:00 p.m.-3:30 p.m. PST.
  • Abstract #546 Oral Presentation: First-line pembrolizumab (pembro)
    monotherapy for advanced non-clear cell renal cell carcinoma (nccRCC):
    Results from KEYNOTE-427 cohort B. D. McDermott. Saturday, Feb. 16.
    2:00 p.m.-3:30 p.m. PST.

Prostate Cancer

  • Abstract #145 Rapid Abstract Session: KEYNOTE-365 cohort A:
    Pembrolizumab (pembro) plus olaparib in docetaxel-pretreated patients
    (pts) with metastatic castrate-resistant prostate cancer (mCRPC). E.
    Yu. Thursday, Feb. 14. 4:35 p.m.-5:30 p.m. PST.
  • Abstract #170 Poster Session: KEYNOTE-365 cohort B: Pembrolizumab
    (pembro) plus docetaxel and prednisone in abiraterone (abi) or
    enzalutamide (enza)-pretreated patients (pts) with metastatic castrate
    resistant prostate cancer (mCRPC). C. Massard. Thursday, Feb. 14.
    11:30 a.m.-1:00 p.m. and 5:30 p.m.-6:30 p.m. PST.
  • Abstract #171 Poster Session: KEYNOTE-365 cohort C: Pembrolizumab
    (pembro) plus enzalutamide (enza) in abiraterone (abi)-pretreated
    patients (pts) with metastatic castrate resistant prostate cancer
    (mCRPC). P. Fong. Thursday, Feb. 14. 11:30 a.m.-1:00 p.m. and
    5:30 p.m.-6:30 p.m. PST.
  • Abstract #216 Poster Session: Pembrolizumab for metastatic
    castration-resistant prostate cancer (mCRPC) previously treated with
    docetaxel: Updated analysis of KEYNOTE-199. E. Antonarakis. Thursday,
    Feb. 14. 11:30 a.m.-1:00 p.m. and 5:30 p.m.-6:30 p.m. PST.
  • Abstract #TPS340 Poster Session: PROPEL: A randomized, phase III trial
    evaluating the efficacy and safety of olaparib combined with
    abiraterone as first-line therapy in patients with metastatic
    castration-resistant prostate cancer (mCRPC). N. Clarke. Thursday,
    Feb. 14. 11:30 a.m.-1:00 p.m. and 5:30 p.m.-6:30 p.m. PST.

Bladder Cancer

  • Abstract #350 Welcome and General Session: KEYNOTE-057: Phase II trial
    of Pembrolizumab (pembro) for patients (pts) with high-risk (HR)
    nonmuscle invasive bladder cancer (NMIBC) unresponsive to bacillus
    calmette-guérin (BCG). A. Balar. Friday, Feb. 15. 7:55 a.m.-9:25 a.m.
    PST.
  • Abstract #433 Poster Session: Association between stromal/TGF-β/EMT
    gene expression signature and response to pembrolizumab monotherapy in
    cisplatin-ineligible patients with locally advanced (unresectable) or
    metastatic urothelial carcinoma. P. Grivas. Friday, Feb. 15. 12:15
    p.m.-1:45 p.m. and 5:15 p.m.- 6:15 p.m. PST.

For more information, including a complete list of abstract titles and
presentation dates and times for Merck’s oncology portfolio, please
visit the ASCO GU website at https://gucasym.org/program.

About KEYNOTE-426

KEYNOTE-426 is a randomized, double-arm, Phase 3 trial
(ClinicalTrials.gov, NCT02853331) evaluating the safety and efficacy of
KEYTRUDA in combination with axitinib as first-line treatment for
advanced or metastatic RCC compared to sunitinib. The dual primary
endpoints of the study were OS and PFS, and the key secondary endpoint
was ORR. Additional secondary endpoints were disease control rate (DCR),
number of participants who experienced or discontinued the study due to
an adverse event (AE), duration of response (DOR), PFS at 12, 18 and 24
months and OS at 12, 18 and 24 months. In the trial, 861 patients were
randomly assigned to receive KEYTRUDA 200 mg intravenously every three
weeks plus axitinib 5 mg orally twice daily for up to 24 months, or
sunitinib 50 mg orally once daily for four weeks followed by no
treatment for two weeks, continuously.

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 900 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, 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
nab-paclitaxel, 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 metastatic 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 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 metastatic NSCLC, KEYTRUDA is administered at a fixed dose of 200 mg
every three weeks until disease progression, unacceptable toxicity, or
up to 24 months in patients without disease progression.

When administering KEYTRUDA in combination with chemotherapy, KEYTRUDA
should be administered prior to chemotherapy when given on the same day.
See also the Prescribing Information for 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 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 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 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.

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

Microsatellite Instability-High (MSI-H) Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients
with unresectable or metastatic microsatellite instability-high (MSI-H)
or mismatch repair deficient (dMMR)

  • solid tumors that have progressed following prior treatment and who
    have no satisfactory alternative treatment options, or
  • colorectal cancer that has progressed following treatment with
    fluoropyrimidine, oxaliplatin, and irinotecan.

This indication is approved under accelerated approval based on tumor
response rate and durability of response. Continued approval for this
indication may be contingent upon verification and description of
clinical benefit in the confirmatory trials. The safety and
effectiveness of KEYTRUDA in pediatric patients with MSI-H central
nervous system cancers have not been established.

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

Gastric Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent
locally advanced or metastatic gastric or gastroesophageal junction
(GEJ) adenocarcinoma whose tumors express PD-L1 [combined positive score
(CPS) ≥1] as determined by an FDA-approved test, with disease
progression on or after two or more prior lines of therapy including
fluoropyrimidine- and platinum-containing chemotherapy and if
appropriate, HER2/neu-targeted therapy. This indication is approved
under accelerated approval based on tumor response rate and durability
of response. Continued approval for this indication may be contingent
upon verification and description of clinical benefit in the
confirmatory trials. The recommended dose of KEYTRUDA is a fixed dose of
200 mg 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 a fixed dose of 200 mg 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 a fixed dose of 200 mg 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.

Selected Important Safety Information for KEYTRUDA

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases.
Pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA,
including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%),
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.

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

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.

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 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 Ste

Contacts

Media:
Pamela Eisele
(267) 305-3558
Elizabeth H. Sell
(267)
305-3877

Investors:
Teri Loxam
(908) 740-1986
Peter Dannenbaum
(908)
740-1037

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