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, Facebook 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
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MerckMedia Contacts:Pamela Eisele, 267-305-3558Courtney Ronaldo,
908-236-1108orInvestor Contacts:Teri Loxam, 908-740-1986Justin
Holko, 908-740-1879
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