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October 2, 2015 1:49 pm ET

Patients with EGFR or ALK Genomic Tumor Aberrations Should Have Disease Progression on FDA-Approved Therapy for These Aberrations Prior to Receiving KEYTRUDA

Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced that the U.S. Food and Drug Administration (FDA) has
approved KEYTRUDA^® (pembrolizumab) monotherapy, the company’s
anti-PD-1 (programmed death receptor-1) therapy, at a dose of 2 mg/kg
every three weeks, 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 and who have 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.
Under FDA’s accelerated approval regulations, this indication for
KEYTRUDA is approved 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 is the first and only anti-PD-1 therapy approved for both
squamous and non-squamous metastatic NSCLC. In addition to approving
KEYTRUDA for NSCLC, FDA approved the first companion diagnostic that
will enable physicians to determine the level of PD-L1 expression in a
patient’s tumor. In KEYNOTE-001, the clinical study supporting the FDA
Breakthrough Designation for KEYTRUDA and this approval, KEYTRUDA
demonstrated an overall response rate of 41 percent (n=25/61) in
patients with a PD-L1 expression tumor proportion score (TPS) of 50
percent or more; all responses were partial responses (95% CI, 29, 54).
Eighty-four percent (n=21/25) of those who responded had ongoing
responses, including 11 patients with ongoing responses of six months or
longer. Immune-mediated adverse reactions occurred with KEYTRUDA
including pneumonitis, colitis, hepatitis, hypophysitis,
hyperthyroidism, hypothyroidism, type 1 diabetes mellitus, and
nephritis. Based on the severity of the adverse reaction, KEYTRUDA
(pembrolizumab) should be withheld or discontinued and corticosteroids
administered. Based on its mechanism of action, KEYTRUDA can cause fetal
harm when administered to a pregnant woman. Female patients of
reproductive potential should be advised of the potential hazard to a
fetus. For more information regarding immune-mediated adverse reactions
and use in pregnancy, see “Selected Important Safety Information” below.

“Today’s approval of KEYTRUDA is the result of our deep commitment to
bring the benefits of immunotherapy to cancer patients,” said Dr. Roger
M. Perlmutter, president, Merck Research Laboratories. “Together with
scientists and physicians around the world, we endeavor to improve the
lives of patients suffering from these grievous illnesses.”

“This important news means that we now have a new immunotherapy option
to help patients with squamous and non-squamous metastatic non-small
cell lung cancer with disease progression on or after
platinum-containing chemotherapy and whose tumors express PD-L1. The
durability of response with immune checkpoint inhibitors is exciting and
has given new options for our patients,” said Dr. Naiyer Rizvi, director
of thoracic oncology and director of immunotherapeutics, New York
Presbyterian Hospital, Columbia University Medical Center, and a
principal investigator for the KEYTRUDA lung cancer clinical program.
“And, with the approval of the first PD-L1 companion diagnostic, we can
identify patients who are more likely to experience benefit from
KEYTRUDA.”

KEYTRUDA is an immunotherapy that blocks the interaction between PD-1
and its ligands, PD-L1 and PD-L2, thereby helping the immune system do
what it is meant to do: help detect and fight cancer cells. KEYTRUDA can
also cause the immune system to attack normal organs and tissues.

“We are pleased that today’s approval of KEYTRUDA provides physicians
and patients with a new anti-PD-1 immunotherapy option to help fight
this deadly disease,” said Andrea Ferris, president and chairman,
LUNGevity Foundation. “It is an exciting time as more treatment options
are becoming available that help to combat cancer by harnessing the
power of the body’s own immune system.”

Data Supporting FDA Accelerated Approval in Advanced NSCLC

The accelerated FDA approval was based on a multicenter, open-label
multi-cohort, activity-estimating study (KEYNOTE-001), which evaluated
KEYTRUDA in a cohort of 280 patients with metastatic NSCLC that had
progressed following platinum-containing chemotherapy, and if
appropriate, targeted therapy for EGFR (epidermal growth factor
receptor) or ALK (anaplastic lymphoma kinase) mutations and any evidence
of PD-L1 expression by a clinical trial immunohistochemistry assay. A
prospectively defined subgroup was retrospectively analyzed to evaluate
PD-L1 as a biomarker among 61 patients with a PD-L1 TPS greater than or
equal to 50 percent. Patients received KEYTRUDA monotherapy [10 mg/kg
every two (n=27) or three (n=34) weeks] until unacceptable toxicity or
disease progression. Primary endpoints were overall response rate (ORR)
per RECIST 1.1 and duration of response. In the study, ORR for KEYTRUDA
(pembrolizumab) was 41 percent (n=25/61) in patients with a PD-L1 TPS
greater than or equal to 50 percent; all responses were partial
responses (95% CI, 29, 54). Of the patients who responded, 84 percent
(n=21/25) continued to respond to treatment with KEYTRUDA, including 11
patients with ongoing responses of six months or longer. The ORR and
duration of response were similar regardless of dosing schedule (every 2
weeks or every 3 weeks). In a separate subgroup of 25 patients with
limited follow-up with PD-L1 TPS greater than or equal to 50% receiving
KEYTRUDA at a dose of 2 mg/kg every 3 weeks in KEYNOTE-001, activity was
also observed.

The most common adverse reactions (reported in at least 20% of study
patients) were fatigue (44%), cough (29%), decreased appetite (25%), and
dyspnea (23%).

Merck is conducting multiple Phase 3 clinical studies in advanced NSCLC.

Approval of PD-L1 Companion Diagnostic for Patients with Advanced
NSCLC

In parallel with the approval of KEYTRUDA, the FDA has also given
Pre-Market Approval (PMA) to the first predictive companion diagnostic
for use in detecting PD-L1, an immune-related biomarker expressed on
some tumor cells: the PD-L1 IHC 22C3 pharmDx kit made by Dako North
America, Inc., an Agilent Technologies Company. The data supporting the
approval of KEYTRUDA for metastatic NSCLC showed that 22 percent of
patients (n=61/280) had a PD-L1 TPS greater than or equal to 50 percent.
This companion diagnostic will be available commercially to laboratories
in the U.S. through Dako and testing using the assay will be available
at U.S. reference laboratories including Laboratory Corporation of
America^® Holdings (LabCorp^®), Quest Diagnostics,
and GE Healthcare Clarient Diagnostic Services. These national reference
laboratories do not represent an exclusive network of accredited
pathology laboratories offering PD-L1 testing and PD-L1 testing may be
offered by other accredited pathology laboratories.

Selected Safety Information for KEYTRUDA (pembrolizumab) Injection
100 mg

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 in patients
receiving KEYTRUDA. 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.

Colitis occurred in 4 (0.7%) of 550 patients, including Grade 2 (0.2%)
or 3 (0.4%) colitis in patients receiving KEYTRUDA. 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.

Hepatitis occurred in patients receiving KEYTRUDA (pembrolizumab).
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 indicated. Withhold KEYTRUDA
for Grade 2 and withhold or discontinue for Grade 3 or Grade 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, has occurred
in patients receiving KEYTRUDA. 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.

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.

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 of the adverse reaction to Grade 1 or
less, initiate corticosteroid taper and continue to taper over at least
1 month. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or
less following steroid taper. Permanently discontinue KEYTRUDA for any
severe or 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 patients treated with KEYTRUDA: rash, vasculitis, hemolytic
anemia, serum sickness, myasthenia gravis, bullous pemphigoid, and
Guillain-Barre syndrome.

Infusion-related reactions, including severe and life-threatening
reactions, have occurred in patients receiving KEYTRUDA. Monitor
patients for signs and symptoms of infusion-related reactions including
rigors, chills, wheezing, pruritus, flushing, rash, hypotension,
hypoxemia, and fever. For severe or life-threatening reactions, stop
infusion and permanently discontinue KEYTRUDA.

Based on its mechanism of action, KEYTRUDA (pembrolizumab) 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 patients.
Serious adverse reactions occurred in 38% of patients. The most frequent
serious adverse reactions reported in 2% or more 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%), decreased appetite (25%), dyspnea (23%), and cough
(29%).

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.

Merck’s Commitment to Access for KEYTRUDA

Merck provides multiple programs to help ensure patients who are
prescribed KEYTRUDA have access to our anti-PD-1 therapy. The Merck
Access Program provides reimbursement support for eligible patients
receiving KEYTRUDA, including help with out-of-pocket costs and co-pay
assistance. Merck also offers financial assistance for eligible patients
who are uninsured through our patient assistance program. More
information is available by calling 1-855-257-3932 or visiting www.merckaccessprogram-keytruda.com.

About KEYTRUDA^® (pembrolizumab)

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 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. KEYTRUDA is
also indicated for the treatment of patients with unresectable or
metastatic melanoma and disease progression following ipilimumab and, if
BRAF V600 mutation positive, a BRAF inhibitor. These indications are
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.

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 healthcare 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 healthcare 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 YouTube.

Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA

This news release of Merck & Co., Inc., Kenilworth, NJ, 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 healthcare legislation in the
United States and internationally; global trends toward healthcare 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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