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June 4, 2016 7:00 am ET

New Analysis from KEYNOTE-010, Comparing KEYTRUDA to Chemotherapy, Shows Improved Survival Benefit in Patients with Increased Levels of PD-L1 Expression

KEYNOTE-001 Findings Show Responses Are Durable and Include Two Year Overall Survival Data for KEYTRUDA

KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE: MRK), known as MSD outside the United States and Canada,
today announced new data, including updated response rates,
progression-free survival (PFS) and overall survival (OS) with KEYTRUDA^®
(pembrolizumab), the company’s anti-PD-1 therapy, as a monotherapy in
patients with advanced non-small cell lung cancer (NSCLC) whose tumors
express PD-L1 from two studies: KEYNOTE-010 and KEYNOTE-001. The
findings are being presented at the 52^nd Annual Meeting of
the American Society of Clinical Oncology (ASCO) in Chicago (Abstracts
#9015 and #9026).

A sub-analysis from the phase 2/3 KEYNOTE-010 trial includes OS data
with KEYTRUDA compared to chemotherapy in previously treated patients
with advanced NSCLC based on varying levels of PD-L1 expression; other
data from KEYNOTE-010 are currently under review by the U.S. Food and
Drug Administration (FDA) and are intended to serve as the basis for the
full approval of KEYTRUDA in lung cancer in patients whose tumors
express PD-L1. Additionally, updated findings from the phase 1b
KEYNOTE-001 trial, the study that supported the accelerated approval of
KEYTRUDA in NSCLC, include overall response rate (ORR), PFS, safety and
two-year survival data.

“We are particularly excited by the results we are seeing with KEYTRUDA
in lung cancer from both studies including longer term follow-up data in
KEYNOTE-001 that continues to demonstrate durable responses in
treatment-naïve and treatment-experienced patients,” said Dr. Roger
Dansey, senior vice president and therapeutic area head, oncology
late-stage development, Merck Research Laboratories. “The KEYNOTE-010
data show that there is a correlation between increased levels of PD-L1
expression and improved benefit, which further underscores the
importance of understanding a patient’s PD-L1 expression when
determining a specific treatment plan.”

Merck has a robust clinical development program for KEYTRUDA
(pembrolizumab) in lung cancer, with five registration-enabling studies
currently underway. The KEYTRUDA clinical development program includes
more than 30 tumor types in more than 270 clinical trials, including
more than 100 trials that combine KEYTRUDA with other cancer treatments.

Findings from KEYNOTE-010 (Abstract #9015)

KEYNOTE-010 is a global, open-label, randomized, pivotal phase 2/3 study
evaluating KEYTRUDA (2 mg/kg or 10 mg/kg every three weeks) compared to
standard of care chemotherapy (docetaxel, 75 mg/m² every
three weeks) in patients with previously treated advanced NSCLC. The
primary endpoints were OS and PFS and were assessed based on patients
whose tumors express high levels of PD-L1 (greater than or equal to 50
percent) and in patients with any level of PD-L1 expression (greater
than or equal to one percent) – as reflected by tumor proportion scores
(TPS). KEYNOTE-010 is 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
NSCLC. As previously announced, the study met its primary objective
showing that KEYTRUDA significantly improved OS compared to chemotherapy
in patients with any level of PD-L1 expression. Findings were similar in
patients who received the FDA-approved dose of KEYTRUDA (2 mg/kg every
three weeks) and the investigational dose of KEYTRUDA (10 mg/kg every
three weeks). These findings also served as the basis for the KEYTRUDA
application currently under review by the FDA.

Findings from abstract #9015 were based on a sub-analysis of patient
outcomes across four PD-L1 expression categories as determined by TPS
(one to 24 percent; 25 to 49 percent; 50 to 74 percent; and greater than
or equal to 75 percent) (n=1,033). Results showed that the OS, PFS, and
overall response rate (ORR) generally increased with increasing levels
of PD-L1 expression in those patients treated with KEYTRUDA, but not
chemotherapy (docetaxel) – with the longest OS and PFS and highest ORR
observed in patients who were in the highest PD-L1 TPS category.

In patients treated with KEYTRUDA (pembrolizumab), median OS was 16.6
months in patients in the highest PD-L1 TPS category (95% CI, 11.2-NR)
and 9.7 months in patients in the lowest PD-L1 TPS category (95% CI,
8.9-11.6); median PFS was 6.2 months in patients in the highest PD-L1
TPS category (95% CI, 4.2-8.2) and 2.6 months in the lowest PD-L1 TPS
category (95% CI, 2.1-3.4); ORR was 33.7 percent in patients in the
highest PD-L1 TPS category and 8.6 percent in the lowest PD-L1 TPS
category.

In patients treated with chemotherapy, median OS was 8.2 months in
patients in the highest PD-L1 TPS category (95% CI, 5.8-10.9) and 8.5
months in patients in the lowest PD-L1 TPS category (95% CI, 7.5-9.9);
median PFS was 4.0 months in patients in the highest PD-L1 TPS category
(95% CI, 2.2-4.5) and 4.0 months in the lowest PD-L1 TPS category (95%
CI, 2.3-5.5); ORR was 7.0 percent in patients in the highest PD-L1 TPS
category and 10.9 percent in the lowest PD-L1 TPS category.

The safety profile of KEYTRUDA was consistent with that observed in
previously reported studies of KEYTRUDA.

On June 4, these data will be presented in a poster session from 8:00 –
11:30 a.m. CDT (Location: Hall A) and in a poster discussion from 3:00 –
4:15 p.m. CDT (Location: E354b).

Findings from KEYNOTE-001 (Abstract #9026)

KEYNOTE-001 is a multicenter, open-label, multi-cohort,
activity-estimating phase 1b trial evaluating KEYTRUDA (2 mg/kg every
three weeks or 10 mg/kg every two or three weeks) in various advanced
cancers, including lung cancer. The lung cancer cohort included
treatment-naïve and previously treated patients with advanced NSCLC. The
primary efficacy outcome measure was confirmed ORR as assessed by
blinded independent central review using RECIST v1.1. Tumor response was
assessed every nine weeks. The secondary outcome measures included PFS,
OS, and duration of response. Findings from this study supported the
accelerated approval of KEYTRUDA in previously treated NSCLC based on
ORR and safety data.

Primary outcome measures observed in treatment-naïve patients (n=101)
showed ORR of 58.3 percent (TPS greater than or equal to 50 percent),
17.4 percent (TPS of one to 49 percent), and 10.0 percent (TPS of less
than one percent); and ORR in previously treated patients (n=449) of
38.3 percent (TPS greater than or equal to 50 percent), 12.9 percent
(TPS of one to 49 percent), and 9.9 percent (TPS of less than one
percent). Data at ASCO also assessed secondary outcome measures,
including OS. In treatment-naïve patients, results showed a median OS of
22.1 months (95% CI, 16.8-27.2) with an 18-month OS rate of 58.1 percent
and a 24-month OS rate of 44.5 percent. In previously treated patients,
results showed a median OS of 10.6 months (95% CI, 8.6-13.3) with an
18-month OS rate of 36.6 percent and a 24-month OS rate of 30.4 percent.

Outcomes were further assessed based on three PD-L1 TPS categories
(greater than or equal to 50 percent; one to 49 percent; and less than
one percent). Results of this analysis showed that while a benefit was
observed across all PD-L1 categories, the greatest benefit was observed
in treatment-naïve patients with higher levels of PD-L1 expression
(greater than or equal to 50 percent of cells expressing PD-L1). In this
group, the 18-month OS rate was 72.7 percent and the 24-month OS rate
was 60.6 percent; the median OS had not been reached at the time of
analysis.

The safety profile of KEYTRUDA (pembrolizumab) was consistent with that
observed in previously reported KEYTRUDA studies. Immune-mediated
adverse events of Grade 3-5 were hypothyroidism, pneumonitis,
hyperthyroidism, severe skin toxicities, colitis, adrenal insufficiency,
and hypophysitis. There were two treatment-related deaths (one case each
of interstitial lung disease and cardiopulmonary arrest).

These data will be presented in a poster session on June 4, 8:00 – 11:30
a.m. CDT (Location: Hall A).

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 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. This
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.

KEYTRUDA (pembrolizumab) is administered at a dose of 2 mg/kg as an
intravenous infusion over 30 minutes every three weeks for the approved
indications.

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
and occurred more frequently in patients with a history of
asthma/chronic obstructive pulmonary disease (5.4%) or prior thoracic
radiation (6.0%). 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 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-mediated 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%) hyperthyroidism. Hypothyroidism occurred in 38 (6.9%)
of 550 patients, including Grade 2 (5.5%) or 3 (0.2%) hypothyroidism.
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 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
(pembrolizumab). 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 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% 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 (pembrolizumab) 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.

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 more than 270 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,
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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 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
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