Approval Based on Data Showing Improved
Overall Survival and Progression-Free Survival with KEYTRUDA
Compared to Chemotherapy
First Anti-PD-1 Therapy Approved in Europe
for Previously Untreated Patients with Metastatic NSCLC
Merck (NYSE:MRK), known as MSD outside the United States and
Canada, today announced that the European Commission has approved
KEYTRUDA® (pembrolizumab), the company’s anti-PD-1 therapy, for the
first-line treatment of metastatic non-small cell lung cancer
(NSCLC) in adults whose tumors have high PD-L1 expression (tumor
proportion score [TPS] of 50 percent or more) with no EGFR or ALK
positive tumor mutations.
“The approval of KEYTRUDA as a first treatment instead of
chemotherapy for patients who express high levels of PD-L1 has the
potential to transform the way metastatic non-small cell lung
cancer is treated,” said Dr. Roy Baynes, senior vice
president, head of clinical development, and chief medical officer,
Merck Research Laboratories. “We are committed to ensuring that
patients in Europe – who are in need of new treatment options – are
able to quickly gain access to KEYTRUDA.”
The approval is based on phase 3 data which demonstrated
superior overall survival (OS) and progression-free survival (PFS)
with KEYTRUDA compared to chemotherapy, the current standard of
care for advanced NSCLC. The approval allows marketing of KEYTRUDA
in all 28 EU member states plus Iceland, Lichtenstein and Norway,
at the approved dose of 200 mg every three weeks until disease
progression or unacceptable toxicity. In August 2016, KEYTRUDA
(pembrolizumab) (2 mg/kg every three weeks) was approved in Europe
for previously-treated patients with locally advanced or metastatic
NSCLC whose tumors express PD-L1 (TPS of 1 percent or more) and who
have received at least one prior chemotherapy regimen.
“The data demonstrate that KEYTRUDA provided meaningful
improvements in survival versus the current standard of care in
patients whose tumors express high levels of PD-L1,” said Dr. Luis
Paz-Ares, chair of the medical oncology department, Hospital
Universitario Doce de Octubre, Madrid, Spain. “These findings
supporting the approval also provide further rationale for
biomarker testing in order to identify those patients more likely
to benefit the most from treatment with KEYTRUDA.”
About KEYNOTE-024
The European Commission’s approval is based on data from
KEYNOTE-024, a randomized, open-label, phase 3 study evaluating
KEYTRUDA monotherapy at a fixed dose of 200 mg compared to standard
of care platinum-containing chemotherapy (pemetrexed+carboplatin,
pemetrexed+cisplatin, gemcitabine+cisplatin,
gemcitabine+carboplatin, or paclitaxel+carboplatin) for the
treatment of patients with both squamous and non-squamous
metastatic NSCLC. The study enrolled 305 patients who had not
received prior systemic chemotherapy treatment for their metastatic
disease and whose tumors had high PD-L1 expression with no EGFR or
ALK aberrations. The primary endpoint was PFS; additional efficacy
outcome measures were OS and objective response rate (ORR).
In the study, KEYTRUDA reduced the risk of disease progression
or death by 50 percent compared to chemotherapy (HR, 0.50 [95% CI,
0.37, 0.68]; p<0.001). The median PFS for KEYTRUDA was 10.3
months (95% CI, 6.7-not reached) compared to 6.0 months for
chemotherapy (95% CI, 4.2-6.2). At six months and 12 months,
respectively, 62 percent and 48 percent of patients treated with
KEYTRUDA were alive and had no disease progression compared to 50
percent and 15 percent of those receiving chemotherapy.
Additionally, KEYTRUDA resulted in a 40 percent reduction in the
risk of death compared to chemotherapy (HR, 0.60 [95% CI, 0.41,
0.89]; p=0.005); this finding includes the 66 patients (43.7%) on
the chemotherapy arm who crossed over in-study to receive KEYTRUDA
once their cancer had progressed; median OS was not reached in
either group. The OS rate at six months and 12 months,
respectively, was 80 percent and 70 percent in patients treated
with KEYTRUDA compared to 72 percent and 54 percent in those
receiving chemotherapy.
Further, ORR was 45 percent for patients receiving KEYTRUDA
(pembrolizumab) (95% CI, 37-53), including six complete responses,
compared to 28 percent with chemotherapy (95% CI, 21-36), including
one complete response.
The safety analysis supporting the European approval of KEYTRUDA
was based on 2,953 patients with advanced melanoma or NSCLC across
four doses (2 mg/kg every three weeks, 200 mg every three weeks, or
10 mg/kg every two or three weeks) in studies KEYNOTE-001,
KEYNOTE-002, KEYNOTE-010 and KEYNOTE-024 combined. The most common
adverse reactions (≥10%) with KEYTRUDA were fatigue (24%), rash
(19%), pruritus (17%), 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.
About KEYTRUDA® (pembrolizumab)
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 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 in the U.S.
Melanoma
KEYTRUDA is indicated for the treatment of patients with
unresectable or metastatic melanoma at a dose of 2 mg/kg every
three weeks until disease progression or unacceptable toxicity.
Lung Cancer
KEYTRUDA is indicated for the first-line treatment of patients
with metastatic non-small cell lung cancer (NSCLC) whose tumors
have high PD-L1 expression [tumor proportion score (TPS) ≥50%] as
determined by an FDA-approved test, with no EGFR or ALK genomic
tumor aberrations.
KEYTRUDA is also indicated for the treatment of patients with
metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) 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
(pembrolizumab).
In metastatic NSCLC, KEYTRUDA is administered at a fixed dose of
200 mg every three weeks until disease progression, unacceptable
toxicity, or up to 24 months in patients without disease
progression.
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. 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. In HNSCC, KEYTRUDA is administered at a fixed
dose of 200 mg every three weeks until disease progression,
unacceptable toxicity, or up to 24 months in patients without
disease progression.
Selected Important Safety Information for
KEYTRUDA® (pembrolizumab)
KEYTRUDA can cause immune-mediated pneumonitis, including fatal
cases. Pneumonitis occurred in 94 (3.4%) of 2799 patients receiving
KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%),
and 5 (0.1%) pneumonitis, and occurred more frequently in patients
with a history of prior thoracic radiation (6.9%) compared to those
without (2.9%). 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.
KEYTRUDA can cause immune-mediated colitis. Colitis occurred in
48 (1.7%) of 2799 patients receiving KEYTRUDA, including Grade 2
(0.4%), 3 (1.1%), and 4 (<0.1%) 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.
KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred
in 19 (0.7%) of 2799 patients receiving KEYTRUDA, including Grade 2
(0.1%), 3 (0.4%), and 4 (<0.1%) hepatitis. 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.
KEYTRUDA (pembrolizumab) can cause hypophysitis. Hypophysitis
occurred in 17 (0.6%) of 2799 patients receiving KEYTRUDA,
including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%) hypophysitis.
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.
KEYTRUDA can cause thyroid disorders, including hyperthyroidism,
hypothyroidism, and thyroiditis. Hyperthyroidism occurred in 96
(3.4%) of 2799 patients receiving KEYTRUDA, including Grade 2
(0.8%) and 3 (0.1%) hyperthyroidism. Hypothyroidism occurred in 237
(8.5%) of 2799 patients receiving KEYTRUDA, including Grade 2
(6.2%) and 3 (0.1%) hypothyroidism. Thyroiditis occurred in 16
(0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2
(0.3%) thyroiditis. 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.
KEYTRUDA can cause type 1 diabetes mellitus, including diabetic
ketoacidosis, which have been reported in 6 (0.2%) of 2799
patients. Monitor patients for hyperglycemia or other signs and
symptoms of diabetes. Administer insulin for type 1 diabetes, and
withhold KEYTRUDA and administer antihyperglycemics in patients
with severe hyperglycemia.
KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred
in 9 (0.3%) of 2799 patients receiving KEYTRUDA, including Grade 2
(0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. 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.
KEYTRUDA can cause other clinically important immune-mediated
adverse reactions. 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% (unless otherwise indicated) of
2799 patients: arthritis (1.5%), exfoliative dermatitis, bullous
pemphigoid, rash (1.4%), uveitis, myositis, Guillain-Barré
syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic
anemia, and partial seizures arising in a patient with inflammatory
foci in brain parenchyma.
KEYTRUDA (pembrolizumab) can cause severe or life-threatening
infusion-related reactions, which have been reported in 6 (0.2%) of
2799 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 8% of 682
patients with metastatic NSCLC. The most common adverse event
resulting in permanent discontinuation of KEYTRUDA was pneumonitis
(1.8%). Adverse reactions leading to interruption of KEYTRUDA
occurred in 23% of patients; the most common (≥1%) were diarrhea
(1%), fatigue (1.3%), pneumonia (1%), liver enzyme elevation
(1.2%), decreased appetite (1.3%), and pneumonitis (1%). The most
common adverse reactions (occurring in at least 20% of patients and
at a higher incidence than with docetaxel) were decreased appetite
(25% vs 23%), dyspnea (23% vs 20%), and nausea (20% vs 18%).
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.
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 survival rate for patients
suffering from highly advanced, metastatic (Stage IV) lung cancers
is estimated to be two percent.
Our Focus on Cancer
Our goal is to translate breakthrough science into innovative
oncology medicines to help people with cancer worldwide. At Merck,
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 400 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 over a century, 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.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20170131006176/en/
For MerckMedia:Pamela Eisele, 267-305-3558orCourtney Ronaldo,
908-236-1108orInvestors:Teri Loxam, 908-740-1986orAmy Klug,
908-740-1898
Merck (NYSE:MRK)
Historical Stock Chart
From Mar 2024 to Apr 2024
Merck (NYSE:MRK)
Historical Stock Chart
From Apr 2023 to Apr 2024