Approval Based on Trial Results
Demonstrating Superior Overall Survival Compared to Chemotherapy in
Previously-Treated Patients
Merck (NYSE:MRK), known as MSD outside the United States and
Canada, today announced that the European Commission (EC) has
approved KEYTRUDA® (pembrolizumab), the company’s anti-PD-1
therapy, at a dose of 2 mg/kg every three weeks, for patients with
locally advanced or metastatic non-small cell lung cancer (NSCLC)
in patients whose tumors express PD-L1 and who have received at
least one prior chemotherapy regimen. Patients with EGFR or ALK
positive tumor mutations should also have received approved therapy
for these mutations prior to receiving KEYTRUDA. The EC approval
allows marketing of KEYTRUDA in all 28 EU member states.
The approval is based on findings from KEYNOTE-010, a pivotal
study which showed KEYTRUDA significantly improved overall survival
(OS) compared to standard of care chemotherapy.
“This approval provides an important new treatment regimen for
patients in Europe with advanced lung cancer, one of the most
common and challenging cancers,” said Dr. Roger Dansey, senior vice
president and therapeutic area head, oncology late-stage
development, Merck Research Laboratories. “In the KEYNOTE-010
trial, patients with advanced lung cancer who had failed prior
regimens experienced improved overall survival when treated with
KEYTRUDA as compared with those treated with traditional
chemotherapy.”
“The survival benefit for KEYTRUDA observed in
previously-treated patients who express PD-L1 is promising,” said
Dr. Luis Paz-Ares, chair of the medical oncology department,
Hospital Universitario, Madrid, Spain. “There is a significant
unmet need for lung cancer patients, and with this
approval, we now have a new personalized treatment option
which uses biomarker testing to predict which patients are most
likely to benefit from treatment.”
About KEYNOTE-010
KEYNOTE-010 is a global, open-label, randomized, pivotal phase
2/3 study evaluating KEYTRUDA (pembrolizumab) (2 mg/kg or 10 mg/kg
every three weeks) compared to standard of care chemotherapy
(docetaxel, 75 mg/m2 every three weeks) in 1,033 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 progression-free
survival (PFS) and were assessed based on patients with any level
of PD-L1 expression (greater than or equal to one percent) and in
patients whose tumors express higher levels of PD-L1 (greater than
or equal to 50 percent) – as reflected by tumor proportion score
(TPS).
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 [95% CI, 0.58-0.88;
P=0.001]) and a 39 percent improvement in OS for the 10 mg/kg dose
(HR 0.61 [95% CI, 0.49-0.75; P<0.001]), compared to docetaxel.
Median OS for KEYTRUDA was 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 [95% CI, 0.38-0.77;
P=0.001]) and by 50 percent for the 10 mg/kg dose (HR 0.50 [95% CI,
0.36-0.70; P<0.001]), 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).
Among patients in the total study population 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, 2.6-4.3), compared
to 4.0 months for docetaxel (95% CI, 3.1-4.2). KEYTRUDA numerically
reduced the risk of progression or death (PFS) at both doses (HR
0.88 [95% CI, 0.73-1.04] for 2 mg/kg; HR 0.79 [95% CI, 0.66-0.94]
for 10 mg/kg). PFS results in the overall population were not
statistically significant for either dose based on
protocol-specified statistical testing requirements.
Patients with higher levels of PD-L1 expression who were treated
with KEYTRUDA had significantly prolonged PFS compared to docetaxel
(HR 0.58 [95% CI, 0.43-0.77; P=0.001] for 2 mg/kg; HR 0.59 [95% CI,
0.45-0.78; P<0.001] for 10 mg/kg). Among patients treated with
KEYTRUDA (pembrolizumab) (2 mg/kg and 10 mg/kg, respectively),
median PFS was 5.2 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).
The safety analysis supporting the European approval of KEYTRUDA
was based on 2,799 patients with advanced melanoma or NSCLC across
three doses (2 mg/kg every three weeks or 10 mg/kg every two or
three weeks) in studies KEYNOTE-001, KEYNOTE-002 and KEYNOTE-010
combined. The most common adverse reactions (>10%) with KEYTRUDA
were fatigue (24%), rash (19%), pruritus (18%), diarrhea (12%),
nausea (11%) and arthralgia (10%). The majority of adverse
reactions reported were of Grade 1 or 2 severity. The most serious
adverse reactions were immune-related adverse reactions and severe
infusion-related reactions.
“We are thrilled that the European Union will now have a new
treatment option for certain patients with advanced non-small cell
lung cancer who have not responded to chemotherapy,” said Stefania
Vallone, president, Lung Cancer Europe. “Lung cancer represents the
leading cause of cancer death worldwide, and this milestone
underscores the importance of innovation and commitment to
developing new treatments that can have a positive impact for
patients living with this disease.”
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 two percent.
About KEYTRUDA® (pembrolizumab) Injection 100
mg in the U.S.
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 (pembrolizumab) is also indicated for the treatment of
patients with advanced 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 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 (pembrolizumab)
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.
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 (pembrolizumab).
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 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, 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.
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