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December 5, 2016 10:42 am ET

Data from KEYNOTE-013 Demonstrated Overall Response Rate of 41 Percent, with 86 Percent of Responses Ongoing at the Time of Analysis

KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE: MRK), known as MSD outside the United States and Canada,
announced today study findings demonstrating that KEYTRUDA^®
(pembrolizumab), the company’s anti-PD-1 therapy, achieved an overall
response rate (ORR) of 41 percent (n=7/17) (90% CI, 21-64) with
follow-up of up to 27 months in patients with relapsed or refractory
primary mediastinal large B-cell lymphoma (PMBCL), a type of non-Hodgkin
lymphoma, who were ineligible for or failed to respond to autologous
stem-cell transplantation (ASCT). In patients treated with KEYTRUDA, 86
percent of responses (n=6/7) were ongoing at the time of analysis with
the median duration of response not yet reached (range: 2 to 23 months).
These updated findings, from the ongoing phase 1b KEYNOTE-013 study,
will be presented today at the 58^th Annual Meeting of the
American Society of Hematology (ASH) in San Diego (Abstract #619).
Preliminary findings from this cohort were first presented at the 2015
ASH Annual Meeting.

“For patients with primary mediastinal large B-cell lymphoma who are
ineligible for, or fail to respond to, autologous stem-cell
transplantation, the prognosis is very poor and there are limited
treatment options,” said Pier Luigi Zinzani, M.D., Ph.D., associate
professor of hematology, Institute of Hematology “L. e A. Seràgnoli,”
University of Bologna. “Based on the rarity of this type of blood
cancer, clinical research has been historically limited, and it’s
encouraging to see clinical trials conducted in this disease where we
are seeing durable responses with KEYTRUDA.”

“We are committed to studying immuno-oncology approaches across a broad
spectrum of cancers, including studies in more than 20 hematological
subtypes,” said Dr. Roger Dansey, senior vice president and therapeutic
area head, oncology late-stage development, Merck Research Laboratories.
“These data continue to support the efficacy and safety profile of
KEYTRUDA in primary mediastinal large B-cell lymphoma and the importance
of ongoing evaluation in this patient population.”

The KEYTRUDA (pembrolizumab) clinical development program includes more
than 30 tumor types in nearly 400 clinical trials, including more than
200 trials that combine KEYTRUDA with other cancer treatments. For
hematologic malignancies specifically, Merck is conducting broad
immuno-oncology research assessing the role of monotherapy and
combination regimens with KEYTRUDA. The hematology program includes
nearly 40 ongoing studies – including company sponsored, investigator
sponsored and collaborative studies; several of these are
registration-enabling trials.

Additional Results from KEYNOTE-013 Presented at ASH

KEYNOTE-013 is an ongoing, multi-center, non-randomized, phase 1b trial
of approximately 200 patients evaluating the safety, tolerability, and
efficacy of KEYTRUDA monotherapy in patients with blood cancers,
including myelodysplastic syndromes, multiple myeloma, classical Hodgkin
lymphoma, PMBCL and certain other non-Hodgkin’s lymphomas (or
lymphomata).

These findings are from a cohort of patients with relapsed or refractory
PMBCL who were ineligible for or failed to respond to ASCT. The median
age was 30.5 years (range: 22 to 62 years). Thirty-three percent of
patients had failed prior autologous stem-cell replacement therapy
(n=6/18) and 67 percent (n=12/18) were transplant ineligible. The
co-primary endpoints of the study were ORR and safety; secondary
endpoints included duration of response and complete remission rate.
Patients were initially treated with KEYTRUDA as monotherapy (10 mg/kg
every two weeks) which was later changed by protocol amendment to a
fixed dose (200 mg every three weeks). Seventeen patients were included
in the efficacy analysis.

KEYTRUDA demonstrated an ORR of 41 percent (n=7/17) (90% CI, 21-64), as
assessed by International Harmonization Project Response Criteria, with
a complete remission rate of 12 percent (n=2/17) (90% CI, 2-33) and a
partial remission rate of 29 percent (n=5/17) (90% CI, 12-52).
Additionally, 81 percent of patients (n=13/16) had reduction in target
lesions. The median duration of follow-up was 11 months (range: 3 to 27
months). At the time of analysis, 86 percent of responses were ongoing
(n=6/7) with the median duration of response not yet reached (range: 2
to 23 months). Two patients reached the maximum two years of treatment
and remain in remission (follow-up: 25.4 months, 23.8 months).

Treatment-related adverse events were consistent with previously
reported safety data for KEYTRUDA (pembrolizumab). The most common
treatment-related adverse events were decreased appetite (n=2), diarrhea
(n=2), fatigue (n=2), hypothyroidism (n=2), nausea (n=2), and pyrexia
(n=2). Grade 3 treatment-related adverse events included neutropenia
(n=1) and veno-occlusive liver disease (n=1). Immune-related adverse
events included aggravated diarrhea (n=1) and radiation pneumonitis
(n=1), both grade 2. There were no discontinuations or treatment-related
deaths due to adverse events.

About Primary Mediastinal Large B-Cell Lymphoma (PMBCL)

PMBCL is a rare subtype of diffuse large B-cell lymphoma (a type of
non-Hodgkin lymphoma) that arises in the thymus. PMBCL affects young
adults in their thirties and forties and has a slight female
predominance. It accounts for five to seven percent of all aggressive
lymphomas and two to three percent of all non-Hodgkin lymphomas.

About KEYTRUDA

^®

(pembrolizumab)

KEYTRUDA is a humanized monoclonal antibody that works by increasing the
ability of the body’s immune system to help detect and fight tumor
cells. KEYTRUDA 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.

KEYTRUDA is administered as an intravenous infusion over 30 minutes
every three weeks for the approved indications. KEYTRUDA for injection
is supplied in a 100 mg single use vial.

KEYTRUDA Indications and Dosing

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or
metastatic melanoma at a dose of 2 mg/kg every three weeks until disease
progression or unacceptable toxicity.

Lung Cancer

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

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

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.

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.

Selected Important Safety Information for KEYTRUDA

^®
 (pembrolizumab)

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

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

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

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

KEYTRUDA can cause thyroid disorders, including hyperthyroidism,
hypothyroidism, and thyroiditis. Hyperthyroidism occurred in 96 (3.4%)
of 2799 patients receiving KEYTRUDA, including Grade 2 (0.8%) and 3
(0.1%) hyperthyroidism. Hypothyroidism occurred in 237 (8.5%) of 2799
patients receiving KEYTRUDA, including Grade 2 (6.2%) and 3 (0.1%)
hypothyroidism. The incidence of new or worsening hypothyroidism was
higher in patients with HNSCC occurring in 28 (15%) of 192 patients with
HNSCC, including Grade 3 (0.5%) hypothyroidism. Thyroiditis occurred in
16 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.3%)
thyroiditis. Monitor patients for changes in thyroid function (at the
start of treatment, periodically during treatment, and as indicated
based on clinical evaluation) and for clinical signs and symptoms of
thyroid disorders. Administer replacement hormones for hypothyroidism
and manage hyperthyroidism with thionamides and beta-blockers as
appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4
hyperthyroidism.

KEYTRUDA can cause type 1 diabetes mellitus, including diabetic
ketoacidosis, which have been reported in 6 (0.2%) of 2799 patients.
Monitor patients for hyperglycemia or other signs and symptoms of
diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA
and administer antihyperglycemics in patients with severe hyperglycemia.

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

KEYTRUDA can cause other clinically important immune-mediated adverse
reactions. 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
(pembrolizumab) 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%), exfoliative dermatitis, bullous pemphigoid, rash
(1.4%), uveitis, myositis, Guillain-Barré syndrome, myasthenia gravis,
vasculitis, pancreatitis, hemolytic anemia, and partial seizures arising
in a patient with inflammatory foci in brain parenchyma.

KEYTRUDA can cause severe or life-threatening infusion-related
reactions, which have been reported in 6 (0.2%) of 2799 patients.
Monitor patients for signs and symptoms of infusion-related reactions,
including rigors, chills, wheezing, pruritus, flushing, rash,
hypotension, hypoxemia, and fever. For Grade 3 or 4 reactions, stop
infusion and permanently discontinue KEYTRUDA.

Based on its mechanism of action, KEYTRUDA can cause fetal harm when
administered to a pregnant woman. If used during pregnancy, or if the
patient becomes pregnant during treatment, apprise the patient of the
potential hazard to a fetus. Advise females of reproductive potential to
use highly effective contraception during treatment and for 4 months
after the last dose of KEYTRUDA.

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9%
of 555 patients with advanced melanoma; adverse reactions leading to
discontinuation in more than one patient were colitis (1.4%), autoimmune
hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and
cardiac failure (0.4%). Adverse reactions leading to interruption of
KEYTRUDA occurred in 21% of patients; the most common (≥1%) was diarrhea
(2.5%). The most common adverse reactions with KEYTRUDA vs ipilimumab
were fatigue (28% vs 28%), diarrhea (26% with KEYTRUDA), rash (24% vs
23%), and nausea (21% with KEYTRUDA). Corresponding incidence rates are
listed for ipilimumab only for those adverse reactions that occurred at
the same or lower rate than with KEYTRUDA.

In KEYNOTE-002, KEYTRUDA was discontinued due to adverse reactions in
12% of 357 patients with advanced melanoma; the most common (≥1%) were
general physical health deterioration (1%), asthenia (1%), dyspnea (1%),
pneumonitis (1%), and generalized edema (1%). Adverse reactions leading
to interruption of KEYTRUDA occurred in 14% of patients; the most common
(≥1%) were dyspnea (1%), diarrhea (1%), and maculopapular rash (1%). The
most common adverse reactions with KEYTRUDA vs chemotherapy were fatigue
(43% with KEYTRUDA), pruritus (28% vs 8%), rash (24% vs 8%),
constipation (22% vs 20%), nausea (22% with KEYTRUDA), diarrhea (20% vs
20%), and decreased appetite (20% with KEYTRUDA). Corresponding
incidence rates are listed for chemotherapy only for those adverse
reactions that occurred at the same or lower rate than with KEYTRUDA.

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

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

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

Safety and effectiveness of KEYTRUDA have not been established in
pediatric patients.

Our Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology
medicines to help people with cancer worldwide. At Merck, helping people
fight cancer is our passion and supporting accessibility to our cancer
medicines is our commitment. Our focus is on pursuing research in
immuno-oncology and we are accelerating every step in the journey – from
lab to clinic – to potentially bring new hope to people with cancer.

As part of our focus on cancer, Merck is committed to exploring the
potential of immuno-oncology with one of the fastest-growing development
programs in the industry. We are currently executing an expansive
research program that includes nearly 400 clinical trials evaluating our
anti-PD-1 therapy across more than 30 tumor types. We also continue to
strengthen our immuno-oncology portfolio through strategic acquisitions
and are prioritizing the development of several promising
immunotherapeutic candidates with the potential to improve the treatment
of advanced cancers.

For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

About Merck

For 125 years, Merck has been a global health care leader working to
help the world be well. Merck is known as MSD outside the United States
and Canada. 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.
For more information, visit www.merck.com
and connect with us on Twitter,
Facebook,
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 2015 Annual Report on Form 10-K
and the company’s other filings with the Securities and Exchange
Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

Please see Prescribing Information for KEYTRUDA (pembrolizumab) at 

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

 and

Patient Information/Medication Guide for KEYTRUDA at 

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

.

Merck
Media:
Pamela Eisele, 267-305-3558
Kim Hamilton, 908-740-1863
or
Investors:
Teri Loxam, 908-740-1986
Amy Klug, 908-740-1898