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December 19, 2015 10:55 am ET

KEYNOTE-010 Published in The Lancet and to be Presented at the European Society for Medical Oncology (ESMO) Asia 2015 Congress

KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced results from the pivotal KEYNOTE-010 study, the first
study of its kind to evaluate the potential of an immunotherapy compared
to chemotherapy based on prospective measurement of PD-L1 expression in
patients with advanced non-small cell lung cancer (NSCLC). In the Phase
2/3 study, KEYTRUDA^® (pembrolizumab), Merck’s anti-PD-1
(programmed death receptor-1) therapy, significantly improved overall
survival (OS) compared to chemotherapy in patients with any level of
PD-L1 expression, as defined by a tumor proportion score (TPS) of 1
percent or more. The results were published in The Lancet and
will be presented at the European Society for Medical Oncology (ESMO)
Asia 2015 Congress.

“Because lung cancer remains one of the most common and most challenging
cancers to treat, understanding the role that KEYTRUDA can play in
helping patients was essential to our development program. In this study
in patients with PD-L1 expression of one percent or greater, KEYTRUDA
demonstrably improved overall survival compared to chemotherapy in
previously-treated patients with non-small cell lung cancer, including
both squamous and non-squamous histologies,” said Dr. Roger M.
Perlmutter, president, Merck Research Laboratories.

Merck plans to submit a supplemental Biologics License Application
(sBLA) to the U.S. Food and Drug Administration for KEYTRUDA based on
findings from KEYNOTE-010 by the end of 2015. The Company plans to
submit a Marketing Authorization Application to the European Medicines
Agency in early 2016.

Overall Survival Findings from KEYNOTE-010

The Phase 2/3 KEYNOTE-010 study included 1,034 patients with advanced
NSCLC with PD-L1 expression (TPS of 1% or more). Similar findings were
shown in patients who received the FDA-approved dose of KEYTRUDA
(pembrolizumab) (2 mg/kg every three weeks) (n=345) and an
investigational dose of KEYTRUDA (10 mg/kg every three weeks) (n=346).
Both groups of patients who received KEYTRUDA were compared to patients
who received docetaxel (n=343). PD-L1 expression was assessed by the
immunohistochemistry companion diagnostic test PD-L1 IHC 22C3 PharmDx,
made by Dako North America, Inc., an Agilent Technologies Company. The
findings from KEYNOTE-010 are based on the final study analysis. The
median follow-up was 13.1 months (IQR, 8.6-17.7).

In the total study population (all levels of PD-L1 expression), both
doses of KEYTRUDA studied significantly improved OS compared with
docetaxel. Specifically, KEYTRUDA resulted in a 29 percent improvement
in OS for the 2 mg/kg dose (HR 0.71, P=0.0008; 95% CI, 0.58-0.88) and a
39 percent improvement in OS for the 10 mg/kg dose (HR 0.61, P<0.0001;
95% CI, 0.49-0.75), compared to docetaxel. The estimated 1-year OS rates
for KEYTRUDA were 43.2 percent and 52.3 percent, respectively, compared
to 34.6 percent for docetaxel. Median OS for KEYTRUDA were 10.4 months
(95% CI, 9.4-11.9) and 12.7 months (95% CI, 10.0-17.3), respectively,
compared to 8.5 months for docetaxel (95% CI, 7.5-9.8).

Among patients with higher levels of PD-L1 expression (a TPS score of 50
percent or greater), OS was superior for both KEYTRUDA doses compared
with docetaxel. Specifically, KEYTRUDA improved OS by 46 percent for the
2 mg/kg dose (HR 0.54, P=0.0002; 95% CI, 0.38-0.77) and by 50 percent
for the 10 mg/kg dose (HR 0.50, P<0.0001; 95% CI, 0.36-0.70), compared
to docetaxel. Median OS for KEYTRUDA (2 mg/kg and 10 mg/kg,
respectively) was 14.9 months (95% CI, 10.4 to not reached) and 17.3
months (95% CI, 11.8 to not reached), compared to 8.2 months for
docetaxel (95% CI, 6.4-10.7).

“This is an exciting time, and studies such as KEYNOTE-010 with KEYTRUDA
are paving the way to a better understanding of how to identify the
right medicine for each patient,” said Dr. Roy Herbst, Chief of Medical
Oncology, Yale Cancer Center and Smilow Cancer Hospital at Yale-New
Haven. “These study findings show KEYTRUDA provided superior overall
survival in patients with advanced lung cancer who had positive PD-L1
expression, and support its potential in the treatment of this disease.”

Additional Findings from KEYNOTE-010

In the total study population, KEYTRUDA (pembrolizumab) prolonged
progression-free survival (PFS) at both doses, though statistical
significance was not met (HR 0.88 [95% CI, 0.74-1.05], P=0.07 for 2
mg/kg; HR 0.79 [95% CI, 0.66-0.94], P=0.004 for 10 mg/kg). Among
patients treated with KEYTRUDA (2 mg/kg and 10 mg/kg, respectively),
median PFS was 3.9 months (95% CI, 3.1-4.1) and 4.0 months (95% CI,
2.7-4.3), compared to 4.0 months for docetaxel (95% CI, 3.1-4.2).

Patients with higher levels of PD-L1 expression (a TPS score of 50
percent or greater) who were treated with KEYTRUDA had significantly
prolonged PFS compared to docetaxel (HR 0.59 [95% CI, 0.44-0.78,
P=0.0001] for 2 mg/kg; HR 0.59 [95% CI, 0.45-0.78, P<0.0001] for 10
mg/kg). Among patients treated with KEYTRUDA (2 mg/kg and 10 mg/kg,
respectively), median PFS was 5.0 months (95% CI, 4.0-6.5) and 5.2
months (95% CI, 4.1-8.1), compared to 4.1 months for docetaxel (95% CI,
3.6-4.3).

Additionally, the safety of KEYTRUDA was consistent with what has been
seen in previous trials among advanced lung cancer patients. Grade 3-5
treatment-related adverse events for KEYTRUDA (2 mg/kg and 10 mg/kg,
respectively) included: decreased appetite (n=3, n=1), fatigue (n=4,
n=6), nausea (n=1, n=2), rash (n=1, n=1), diarrhea (n=2, n=0), asthenia
(n=1, n=2), stomatitis (n=0, n=1), and anemia (n=3, n=1). The most
common immune-mediated adverse events for KEYTRUDA (2 mg/kg and 10
mg/kg, respectively) included: hypothyroidism (8% [n=28], 8% [n=28]),
hyperthyroidism (4% [n=12], 6% [n=20]), and pneumonitis (5% [n=16], 4%
[n=15]). There were three treatment-related deaths among patients
receiving KEYTRUDA at the 2 mg/kg dose (pneumonitis [n=2], pneumonia
[n=1]) and three treatment-related deaths among patients receiving
KEYTRUDA at the 10 mg/kg dose (myocardial infarction [n=1], pneumonia
[n=1], and pneumonitis [n=1]).

About KEYNOTE-010 and the KEYTRUDA Development Program

KEYNOTE-010 is a global, open-label, randomized, pivotal Phase 2/3 study
(ClinicalTrials.gov, NCT01905657) evaluating two doses of KEYTRUDA (2
mg/kg or 10 mg/kg every three weeks) compared to docetaxel (75 mg/m^2
every three weeks) in 1,034 patients with squamous and non-squamous
NSCLC who experienced disease progression after platinum-containing
systemic therapy and whose tumors expressed PD-L1. The primary endpoints
were OS and PFS. Tumor response was assessed at week 9, then every 9
weeks thereafter per RECIST 1.1 criteria by independent, central,
blinded, radiographic review and investigator-assessed, immune-related
response criteria.

The KEYTRUDA program currently addresses more than 30 tumor types in
more than 160 clinical trials, including more than 80 combinations of
KEYTRUDA with other cancer treatments. In lung cancer, KEYTRUDA is being
studied across lines of therapy, both as a monotherapy and in
combination with chemotherapy. Registration-enabling trials of KEYTRUDA
(pembrolizumab) are currently enrolling patients in melanoma, NSCLC,
head and neck cancer, bladder cancer, gastric cancer, colorectal cancer,
esophageal cancer, breast cancer, Hodgkin lymphoma, multiple myeloma and
other tumors, with further trials in planning for other cancers.

About Lung Cancer

Lung cancer, which forms in the tissues of the lungs, usually within
cells lining the air passages, is the leading cause of cancer death
worldwide. Each year, more people die of lung cancer than die of colon,
breast, and prostate cancers combined. The two main types of lung cancer
are non-small-cell and small-cell. NSCLC is the most common type of lung
cancer, accounting for about 85 percent of all cases. The five-year
relative survival rate for patients suffering from highly advanced,
metastatic (Stage IV) lung cancers is estimated to be four percent.

About KEYTRUDA (pembrolizumab) Injection 100 mg

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 indicated in the United States at a dose of 2 mg/kg
administered as an intravenous infusion over 30 minutes every three
weeks for the treatment of patients with unresectable or metastatic
melanoma.

KEYTRUDA is also indicated for the treatment of patients with metastatic
non-small cell lung cancer (NSCLC) whose tumors express PD-L1 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. The NSCLC
indication is approved under accelerated approval based on tumor
response rate and durability of response. An improvement in survival or
disease-related symptoms has not yet been established. Continued
approval for this indication may be contingent upon verification and
description of clinical benefit in the confirmatory trials.

Selected Important Safety Information for KEYTRUDA (pembrolizumab)

Immune-mediated pneumonitis occurred in 19 (3.5%) of 550 patients,
including Grade 2 (1.1%), 3 (1.3%), 4 (0.4%), or 5 (0.2%) pneumonitis.
Monitor patients for signs and symptoms of pneumonitis. Evaluate
suspected pneumonitis with radiographic imaging. Administer
corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA
(pembrolizumab) for Grade 2; permanently discontinue KEYTRUDA for Grade
3 or 4 or recurrent Grade 2 pneumonitis.

Immune-mediated colitis occurred in 4 (0.7%) of 550 patients, including
Grade 2 (0.2%) or 3 (0.4%) 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.

Immune-mediate hepatitis occurred in patients receiving KEYTRUDA.
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.

Hypophysitis occurred in 1 (0.2%) of 550 patients, which was Grade 3 in
severity. 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.

Hyperthyroidism occurred in 10 (1.8%) of 550 patients, including Grade 2
(0.7%) or 3 (0.3%). Hypothyroidism occurred in 38 (6.9%) of 550
patients, including Grade 2 (5.5%) or 3 (0.2%). Thyroid disorders can
occur at any time during treatment. 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 Grade 4 hyperthyroidism.

Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 3
(0.1%) of 2117 patients. Monitor patients for hyperglycemia or other
signs and symptoms of diabetes. Administer insulin for type 1 diabetes,
and withhold KEYTRUDA and administer anti-hyperglycemics in patients
with severe hyperglycemia.

Immune-mediated nephritis occurred in patients receiving KEYTRUDA.
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.

Other clinically important immune-mediated adverse reactions can occur.
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 steroid taper. Permanently discontinue KEYTRUDA
(pembrolizumab) for any Grade 3 immune-mediated adverse reaction that
recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant, immune-mediated adverse reactions
occurred in less than 1% of 550 patients: rash, vasculitis, hemolytic
anemia, serum sickness, and myasthenia gravis.

Severe and life-threatening infusion-related reactions have been
reported in 3 (0.1%) of 2117 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.

KEYTRUDA was discontinued due to adverse reactions in 14% of 550
patients. Serious adverse reactions occurred in 38% of patients. The
most frequent serious adverse reactions reported in at least 2% of
patients were pleural effusion, pneumonia, dyspnea, pulmonary embolism,
and pneumonitis. The most common adverse reactions (reported in at least
20% of patients) were fatigue (44%), cough (29%), decreased appetite
(25%), and dyspnea (23%)

No formal pharmacokinetic drug interaction studies have been conducted
with KEYTRUDA. 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 Oncology,
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. For more information about our oncology clinical trials,
visit www.merck.com/clinicaltrials.

About Merck

Today’s Merck is 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,
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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 United States 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 2014 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 the Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf

Merck
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