FDA Approves Merck’s KEYTRUDA® (pembrolizumab) for Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy
August 8, 2016 5:45 am ET
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), the company’s anti-PD-1
(programmed death receptor-1) therapy, at a fixed dose of 200 mg every
three weeks, 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. Under the FDA’s
accelerated approval regulations, this indication for KEYTRUDA is
approved 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. For HNSCC patients, PD-L1 testing is not needed prior to use of
KEYTRUDA.
The approval is based on data from the KEYNOTE-012 study, which included
patients with recurrent or metastatic HNSCC who had disease progression
on or after platinum-containing chemotherapy or following
platinum-containing chemotherapy administered as part of induction,
concurrent, or adjuvant therapy and ECOG performance status (PS) of zero
or one. The data showed an objective response rate (ORR) of 16 percent
(95% CI: 11, 22), complete response rate of five percent, with responses
of six months or longer observed in 82 percent (n=23/28) of the
responding patients. ORR and duration of response were similar
regardless of human papilloma virus (HPV) status.
Immune-mediated adverse reactions occurred with KEYTRUDA including
pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. Based
on the severity of the adverse reaction, KEYTRUDA 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 represents a meaningful advance for the oncology
community, as well as for our head and neck cancer clinical program,”
said Dr. Roger M. Perlmutter, president, Merck Research Laboratories.
“Together with prior approvals in the treatment of other tumor types,
today’s action by the FDA underscores our tireless commitment to
addressing the unmet needs of patients suffering from a broad range of
cancers.”
KEYNOTE-012 was the first clinical study to investigate the role of a
PD-1 inhibitor in patients with recurrent or metastatic HNSCC with
disease progression on or after platinum-containing chemotherapy. Merck
currently has the largest immuno-oncology clinical development program,
including multiple registration-enabling studies in head and neck
cancer, and is conducting research investigating KEYTRUDA
(pembrolizumab) as a monotherapy, as well as in combination with
chemotherapy compared to the current standard of care.
“Head and neck cancer is a complex disease that historically has been
associated with high recurrence rates and poor long-term outcomes,
highlighting the critical need for new treatment options,” said Dr.
Tanguy Seiwert, associate director of the Head and Neck Cancer Program
and assistant professor of medicine at The University of Chicago. “The
approval of KEYTRUDA for previously treated patients with recurrent or
metastatic head and neck squamous cell carcinoma is an important step
forward in treating this disease.”
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.
“Head and neck squamous cell carcinoma presents unique challenges
including limited treatment options, especially for patients with
recurrent or metastatic disease,” said Holly Boykin, executive director,
Head and Neck Cancer Alliance. “We welcome the approval of KEYTRUDA as a
new treatment option for people whose lives are impacted by this
devastating disease.”
Data Supporting the Approval
The accelerated FDA approval was based on a multicenter, nonrandomized,
open-label, multi-cohort phase 1b study, KEYNOTE-012, that evaluated
safety in 192 patients with recurrent or metastatic HNSCC and ECOG PS of
zero or one; efficacy was evaluated in 174 of these patients who had
disease progression on or after platinum-containing chemotherapy
administered for recurrent or metastatic HNSCC or following
platinum-containing chemotherapy administered as part of induction,
concurrent, or adjuvant therapy. Patients were enrolled regardless of
tumor HPV status (33% were HPV-positive). The median number of prior
lines of therapy administered for the treatment of HNSCC was two. Nearly
all (95%) of the patients enrolled had prior radiation therapy. Patients
received KEYTRUDA (pembrolizumab) at a dose of 10 mg/kg every two weeks
(n=53) or a 200 mg fixed dose every three weeks (n=121) until
unacceptable toxicity or disease progression. Patients without disease
progression were treated for up to 24 months. Treatment with KEYTRUDA
could be reinitiated for subsequent disease progression and administered
for up to one additional year. The primary efficacy outcome measures
were ORR according to Response Evaluation Criteria in Solid Tumors
(RECIST) v1.1, as assessed by blinded independent central review (BICR),
and duration of response.
Efficacy analysis showed an ORR of 16 percent (95% CI: 11, 22) with a
complete response rate of five percent. The median follow-up time was
8.9 months. Among the 28 responding patients, the median duration of
response had not been reached (range 2.4+ to 27.7+ months), with 23
patients having responses of six months or longer. The ORR and duration
of response were similar irrespective of dosage regimen (10 mg/kg every
2 weeks or 200 mg every 3 weeks) or HPV status.
In HNSCC, serious adverse reactions occurred in 45 percent of patients
receiving KEYTRUDA. The most frequent serious adverse reactions reported
in at least two percent of patients were pneumonia, dyspnea, confusional
state, vomiting, pleural effusion, and respiratory failure. The
incidence of adverse reactions, including serious adverse reactions, was
similar between dosage regimens (10 mg/kg every 2 weeks or 200 mg every
3 weeks). The most common adverse reactions (reported in at least 20% of
patients) were fatigue (46%), decreased appetite (22%), and dyspnea
(20%). Adverse reactions in patients with HNSCC were generally similar
to those occurring in patients with melanoma and non-small cell lung
cancer (NSCLC), with the exception of increased incidences of facial
edema (10% all Grades; 2.1% Grades 3-4) and new or worsening
hypothyroidism.
About KEYTRUDA
®
(pembrolizumab)
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.
Lung Cancer
KEYTRUDA is 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, at a dose of 2 mg/kg every three
weeks. Patients with EGFR or ALK genomic tumor aberrations should have
disease progression on FDA-approved therapy for these aberrations prior
to receiving KEYTRUDA (pembrolizumab). 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.
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 at a fixed dose
of 200 mg every three weeks. 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.
Selected Important Safety Information for KEYTRUDA
®
(pembrolizumab)
Immune-mediated pneumonitis, including fatal cases, occurred in patients
receiving KEYTRUDA. Monitor patients for signs and symptoms of
pneumonitis. Evaluate suspected pneumonitis with radiographic imaging
and 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 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.
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 patients receiving KEYTRUDA. 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.
New or worsening hypothyroidism occurred in 28 (14.6%) of 192 patients,
including Grade 3 (0.5%) 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
(pembrolizumab) for Grade 3 or 4 hyperthyroidism.
Type 1 diabetes mellitus, including diabetic ketoacidosis, 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.
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 corticosteroid taper. Permanently discontinue KEYTRUDA for any
Grade 3 immune-mediated adverse reaction that recurs and for any
life-threatening immune-mediated adverse reaction.
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 (pembrolizumab) was discontinued due to adverse reactions in 17
percent of 192 patients. Serious adverse reactions occurred in 45
percent of patients. The most frequent serious adverse reactions
reported in at least 2 percent 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 (46%), decreased appetite (22%), and dyspnea (20%).
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.
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 300 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 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
or
An Phan, 908-255-6325
or
Investor:
Teri Loxam, 908-740-1898
or
Amy Klug, 908-740-1898
