Final Overall Survival Data from KEYNOTE-006
To Be Presented at ASCO; KEYTRUDA, the First Anti-PD-1 Monotherapy
to Demonstrate Overall Survival Compared to Ipilimumab, Shows
Continued Benefit with Longer Follow-Up
KEYNOTE-001 Findings Show Continued Benefit
in Response Rates, Duration of Response, and Include New Three-Year
Overall Survival Data for KEYTRUDA
Merck (NYSE:MRK), known as MSD outside the United States and
Canada, today announced final overall survival (OS) data from
KEYNOTE-006 and new findings from KEYNOTE-001, including updated
response rates, duration of response data and three-year OS data
with KEYTRUDA® (pembrolizumab), the company’s anti-PD-1 therapy, in
patients with unresectable or metastatic melanoma. Findings from
the final OS analysis from KEYNOTE-006, a phase 3 study evaluating
KEYTRUDA as monotherapy compared to ipilimumab, continue to show a
significant survival benefit compared to ipilimumab in the
first-line setting for advanced melanoma. These data will be
presented at the 52nd Annual Meeting of the American Society of
Clinical Oncology (ASCO) in Chicago, June 3 – 7, 2016.
Long-term OS data from KEYNOTE-006 to be presented at ASCO
showed that with KEYTRUDA, 55.1 percent and 55.3 percent of
patients were alive two years after starting treatment (10 mg/kg
every two weeks and three weeks, respectively), compared to 43
percent of patients receiving ipilimumab (hazard ratio: 0.68 [95%
CI, 0.53-0.87; p=0.0008] and hazard ratio: 0.68 [95% CI, 0.53-0.86;
p=0.0008], respectively). These data will be presented by Dr. Jacob
Schachter, Ella Institute for Research and Treatment of Melanoma,
Sheba Medical Center, in an oral session on Monday, June 6, from
2:27 to 2:39 p.m. CDT (Location: Arie Crown Theater) (Abstract
#9504).
Additionally, data from KEYNOTE-001, including the long-term,
three-year OS analysis, were featured in the official ASCO Press
Program today and will be presented at ASCO in Chicago. The primary
efficacy measure in KEYNOTE-001 was overall response rate (ORR),
and secondary outcome measures included duration of response,
progression-free survival (PFS) and OS. The data from KEYNOTE-001
discussed today will be presented along with additional findings in
an oral session by Dr. Caroline Robert, Institut Gustave-Roussy, on
Monday, June 6, from 2:15 to 2:27 p.m. CDT (Location: Arie Crown
Theater) (Abstract #9503).
“With longer-term follow-up from two studies, including a
head-to-head trial demonstrating superior survival compared to
another immunotherapy, we are continuing to see durability of
response with KEYTRUDA as monotherapy,” said Dr. Roger Dansey,
senior vice president and therapeutic area head, oncology
late-stage development, Merck Research Laboratories. “These results
add to the growing body of data supporting the use of KEYTRUDA as
first-line treatment in advanced melanoma, and serve as an
important reminder for what we are aiming to achieve through our
immuno-oncology development program – enhanced survival for people
with cancer.”
Findings from the melanoma cohorts of the phase 1b KEYNOTE-001
trial, which included 655 patients, showed an ORR of 33 percent
(per RECIST v1.1). At the time of the analysis, a response duration
of two years or more was observed in 73 percent of patients.
Long-term OS data showed an estimated 40 percent of patients were
alive three years after starting treatment with
KEYTRUDA (pembrolizumab), with a median survival of 24.4 months
(95% CI, 20.2-29.0). Median duration of response has not yet been
reached (range, 1.3+ to 38.8+).
Data from KEYNOTE-001 served as the basis for the U.S. Food and
Drug Administration’s accelerated approval of KEYTRUDA in September
2014. The label was subsequently updated to reflect data from the
KEYNOTE-006 (phase 3) and KEYNOTE-002 (phase 2) trials, expanding
the indication to include treatment of first-line advanced melanoma
regardless of BRAF status. Today, KEYTRUDA is approved for the
treatment of advanced melanoma in more than 50 countries, including
the United States and throughout Europe.
The KEYTRUDA clinical development program includes more than 30
tumor types in more than 270 clinical trials, including more than
100 trials that combine KEYTRUDA with other cancer treatments.
Key Findings from the KEYNOTE-006 Study
KEYNOTE-006 is a global, open-label, randomized, pivotal, phase
3 study evaluating KEYTRUDA (pembrolizumab) compared to ipilimumab
in patients with unresectable stage III or IV advanced melanoma
with no more than one prior systemic therapy. The study randomized
834 patients to receive KEYTRUDA 10 mg/kg every three weeks,
KEYTRUDA 10 mg/kg every two weeks, or four cycles of ipilimumab 3
mg/kg every three weeks. The co-primary endpoints were PFS and OS;
secondary endpoints were ORR, duration of response and safety, with
an exploratory analysis for health-related quality of life (QoL).
Tumor response was assessed at week 12, then every 6 weeks
thereafter per RECIST v1.1 by independent, central, blinded
radiographic review and investigator-assessed, immune-related
response criteria.
Based on data to be presented at ASCO, KEYTRUDA (10 mg/kg every
two or three weeks) continued to provide superior OS, PFS and ORR
compared to ipilimumab. Specifically, long-term OS data showed 55.1
percent and 55.3 percent of patients were alive two years after
starting treatment with KEYTRUDA (every two weeks and three weeks,
respectively) compared to 43 percent of patients receiving
ipilimumab (hazard ratio: 0.68 [95% CI, 0.53-0.87; p=0.0008] and
hazard ratio: 0.68 [95% CI, 0.53-0.86; p=0.0008], respectively).
Median OS was not reached for KEYTRUDA; for ipilimumab, median OS
was 16 months.
Additionally, an estimated 31.2 percent and 27.8 percent of
patients receiving KEYTRUDA (every two weeks and three weeks,
respectively) were alive and were disease progression-free at two
years compared to 13.5 percent of patients receiving ipilimumab
(hazard ratio: 0.61 [95% CI, 0.50-0.75; p<0.0001] for both). For
patients receiving KEYTRUDA, ORR was 36.9 percent and 36.1 percent
(every two weeks and three weeks, respectively) compared to 13.3
percent for patients receiving ipilimumab (p<0.0001 for both
groups).
With longer follow-up, adverse events have remained consistent
with previously reported safety data. There was one
treatment-related death (due to sepsis) in the KEYTRUDA every two
week group.
Key Findings from the KEYNOTE-001 Study
KEYNOTE-001 is a phase 1b multicenter, open-label, multi-cohort
trial evaluating KEYTRUDA in various advanced cancers, including
advanced melanoma. Patients in the melanoma cohorts received 2
mg/kg or 10 mg/kg of KEYTRUDA every three weeks or 10 mg/kg of
KEYTRUDA every two weeks until unacceptable toxicity or disease
progression. The major efficacy outcome measure was confirmed ORR
as assessed by blinded independent central review using RECIST
v1.1. Tumor response was assessed every 12 weeks. The secondary
outcome measures included PFS, OS and duration of response.
The findings to be presented at ASCO include updated response
rates and duration of response data, as well as three-year OS data
from the 655 patients with unresectable or metastatic melanoma and
progression of disease. All patients were followed for at least two
years, with some being followed for almost four years (with median
follow-up duration of 32 months).
Of those patients who responded to treatment with KEYTRUDA
(pembrolizumab), a complete response (CR) was observed in 10
percent of patients. Among the 61 patients who stopped treatment
once a complete response had occurred, the response duration ranged
from 17+ to 44+ months (median duration not reached). Only two
patients who had a complete response experienced disease
progression after stopping treatment. In addition, long-term
survival data showed that 40 percent of patients survived three
years after starting treatment with KEYTRUDA (n=655).
With longer follow-up, adverse events have remained consistent
with previously reported safety data. Immune-mediated
treatment-related adverse events observed in this trial were
hypothyroidism (9.6%), pneumonitis (4.3%), hyperthyroidism (2.3%),
colitis (2.3%), uveitis (1.5%), hepatitis (0.9%), and nephritis
(0.5%).
About KEYTRUDA® (pembrolizumab) Injection 100
mg
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 is also 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. Patients
with EGFR or ALK genomic tumor aberrations should have disease
progression on FDA-approved therapy for these aberrations prior to
receiving KEYTRUDA. 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.
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, including fatal cases, occurred in
patients receiving KEYTRUDA. Pneumonitis occurred in 32 (2.0%) of
1567 patients, including Grade 1 (0.8%), 2 (0.8%), and 3 (0.4%)
pneumonitis. 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 31 (2%) of 1567 patients,
including Grade 2 (0.5%), 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.
Immune-mediated hepatitis occurred in 16 (1%) of 1567 patients,
including Grade 2 (0.1%), 3 (0.7%), 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.
Hypophysitis occurred in 13 (0.8%) of 1567 patients, including
Grade 2 (0.3%), 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.
Hyperthyroidism occurred in 51 (3.3%) of 1567 patients,
including Grade 2 (0.6%) and 3 (0.1%) hyperthyroidism.
Hypothyroidism occurred in 127 (8.1%) of 1567 patients, including
Grade 3 (0.1%) 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 and administer
anti-hyperglycemics in patients with severe hyperglycemia.
Immune-mediated nephritis occurred in 7 (0.4%) of 1567 patients,
including Grade 2 (0.2%), 3 (0.2%), 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.
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
(pembrolizumab) 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
1567 patients: arthritis (1.6%), exfoliative dermatitis, bullous
pemphigoid, uveitis, myositis, Guillain-Barré syndrome, myasthenia
gravis, vasculitis, pancreatitis, hemolytic anemia, and partial
seizures arising in a patient with inflammatory foci in brain
parenchyma.
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.
In Trial 6, KEYTRUDA was discontinued due to adverse reactions
in 9% of 555 patients; adverse reactions leading to discontinuation
in more than one patient were colitis (1.4%), autoimmune hepatitis
(0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and
cardiac failure (0.4%). Adverse reactions leading to interruption
of KEYTRUDA occurred in 21% of patients; the most common (≥1%) was
diarrhea (2.5%). The most common adverse reactions with KEYTRUDA vs
ipilimumab were fatigue (28% vs 28%), diarrhea (26% with KEYTRUDA),
rash (24% vs 23%), and nausea (21% with KEYTRUDA). Corresponding
incidence rates are listed for ipilimumab only for those adverse
reactions that occurred at the same or lower rate than with
KEYTRUDA.
In Trial 2, KEYTRUDA was discontinued due to adverse reactions
in 12% of 357 patients; the most common (≥1%) were general physical
health deterioration (1%), asthenia (1%), dyspnea (1%), pneumonitis
(1%), and generalized edema (1%). Adverse reactions leading to
interruption of KEYTRUDA (pembrolizumab) occurred in 14% of
patients; the most common (≥1%) were dyspnea (1%), diarrhea (1%),
and maculo-papular rash (1%). The most common adverse reactions
with KEYTRUDA (pembrolizumab) vs chemotherapy were fatigue (43%
with KEYTRUDA), pruritus (28% vs 8%), rash (24% vs 8%),
constipation (22% vs 20%), nausea (22% with KEYTRUDA), diarrhea
(20% vs 20%), and decreased appetite (20% with KEYTRUDA).
Corresponding incidence rates are listed for chemotherapy only for
those adverse reactions that occurred at the same or lower rate
than with KEYTRUDA.
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.
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 270 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.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20160518006541/en/
MerckMedia:Pamela Eisele, 267-305-3558An Phan,
908-255-6325orInvestors:Teri Loxam, 908-740-1986Justin Holko,
908-740-1879
Merck (NYSE:MRK)
Historical Stock Chart
From Mar 2024 to Apr 2024
Merck (NYSE:MRK)
Historical Stock Chart
From Apr 2023 to Apr 2024