Results from KEYNOTE-010 Include Improved
Patient-Reported Health-Related Quality of Life Outcomes and
18-Month Findings of Overall Survival and Progression-Free Survival
in Previously Treated Patients Whose Tumors Express PD-L1 (Tumor
Proportion Score of One Percent or More)
Merck (NYSE:MRK), known as MSD outside the
United States and Canada, today announced that KEYTRUDA®
(pembrolizumab), the company’s anti-PD-1 therapy, demonstrated
superiority in overall survival (OS) at 18 months compared to
standard of care chemotherapy (docetaxel) in patients with
metastatic non-small cell lung cancer (NSCLC) previously treated
with platinum-containing chemotherapy whose tumors expressed PD-L1
(tumor proportion score [TPS] of one percent or more), as well as
patients with high levels of PD-L1 expression (TPS of 50 percent or
more). These data, from the phase 2/3 KEYNOTE-010 trial, will be
presented at the ESMO 2016 Congress, the annual meeting of the
European Society for Medical Oncology, in Copenhagen (Abstract
#LBA48).
“These findings – which show superior survival with longer
follow-up across patients with PD-L1 expression (tumor proportion
score of one percent or more), as well as improved quality of life
– point to KEYTRUDA as a durable treatment option for many
previously treated patients with advanced non-small cell lung
cancer,” said Roy S. Herbst, M.D., Ph.D., professor of medicine and
chief of medical oncology, Yale Cancer Center and Smilow Cancer
Hospital at Yale New Haven. “These data also reinforce the value of
using PD-L1 as a biomarker to identify patients who are likely to
benefit from KEYTRUDA.”
In additional data at the ESMO 2016 Congress from KEYNOTE-010,
an analysis of patient-reported health-related quality of life
outcomes showed more patients treated with KEYTRUDA (pembrolizumab)
reported positive outcomes compared to patients treated with
chemotherapy (Abstract #1219P).
Separately at the ESMO 2016 Congress, researchers presented an
analysis of PD-L1 prevalence across three separate studies,
including KEYNOTE-010. Overall, 66 percent of patients with
metastatic NSCLC expressed any level of PD-L1, and 28 percent
expressed high levels of PD-L1 (Abstract #1060P).
“Our research in immuno-oncology continues to show tremendous
promise, with our goal being to extend the lives of significant
numbers of patients with non-small cell lung cancer,” said Roger
Dansey, M.D., senior vice president and therapeutic area head,
oncology late-stage development, Merck Research Laboratories. “In
this longer-term analysis of KEYNOTE-010, among patients who
responded to treatment, four times as many patients receiving
KEYTRUDA were still alive without disease progression compared to
docetaxel. It is gratifying to see these results continue with
additional follow-up.”
Merck has a robust clinical development program for KEYTRUDA in
lung cancer, with multiple registration-enabling studies currently
underway. The KEYTRUDA clinical development program includes more
than 30 tumor types in more than 350 clinical trials, including
more than 100 trials that combine KEYTRUDA with other cancer
treatments.
Efficacy and Safety Findings from KEYNOTE-010 (Abstract
#LBA48)
KEYNOTE-010 is a global, open-label, randomized, pivotal phase
2/3 study evaluating KEYTRUDA (2 mg/kg or 10 mg/kg every three
weeks) compared to standard of care chemotherapy (docetaxel, 75
mg/m2 every three weeks) in patients with previously treated
metastatic NSCLC. The primary endpoints were OS and
progression-free survival (PFS) and were assessed based on patients
whose tumors expressed PD-L1 (TPS of one percent or more) and high
levels of PD-L1 (TPS of 50 percent or more). Secondary endpoints
included overall response rate (ORR) and duration of response.
KEYNOTE-010 is the first study of its kind to evaluate the
potential of an immunotherapy compared to chemotherapy based on
prospective measurement of PD-L1 expression in patients with
metastatic NSCLC. As previously announced, the study met its
primary objective, showing that KEYTRUDA significantly improved OS
compared to chemotherapy in patients with PD-L1 expression (TPS of
one percent or more). Findings were similar in patients who
received the FDA-approved dose of KEYTRUDA (2 mg/kg every three
weeks) and an investigational dose of KEYTRUDA (10 mg/kg every
three weeks). These data also served as the basis for the KEYTRUDA
(pembrolizumab) application approval by the European Medicines
Agency (EMA) in July of this year and are currently under review by
the U.S. Food and Drug Administration (FDA) for the second-line or
greater NSCLC treatment setting.
At the ESMO 2016 Congress, data from this study of 1,034
patients included six months of additional follow-up, with a median
follow-up of 19.2 months (range, 11.7-29.7), and showed superior
outcomes of OS, PFS, and ORR with KEYTRUDA compared to docetaxel in
patients with PD-L1 expression (TPS of one percent or more) as well
as high levels of PD-L1 expression (TPS of 50 percent or more) –
with consistency of outcomes across KEYTRUDA doses.
In patients with PD-L1 expression (TPS of one percent or more),
OS at 18 months was 37 percent (HR, 0.72 [95% CI, 0.60-0.87];
p=0.0003) with KEYTRUDA 2 mg/kg, 43 percent (HR, 0.60 [95% CI,
0.50-0.73]; p<0.00001) with KEYTRUDA 10 mg/kg, and 24 percent
with docetaxel. Among all patients, median OS was 10.5 months with
KEYTRUDA 2 mg/kg, 13.6 months with KEYTRUDA 10 mg/kg, and 8.6
months with docetaxel. ORR was 19 percent (95% CI, 15-23,
p=0.00025) with KEYTRUDA 2 mg/kg, 20 percent (95% CI, 16-25,
p=0.00004) with KEYTRUDA 10 mg/kg and 10 percent (95% CI, 7-13)
with docetaxel. Responses to KEYTRUDA continued to be durable;
among patients with any level of PD-L1 expression who responded to
treatment, 60 percent on each of the KEYTRUDA treatment arms were
alive, progression-free, and had not received additional therapy
for their disease, compared to 15 percent in the docetaxel
treatment arm.
In patients with high levels of PD-L1 expression (TPS of 50
percent or more), OS at 18 months was 46 percent (HR, 0.54 [95% CI,
0.39-0.73]; p=0.00004) with KEYTRUDA 2 mg/kg, 52 percent with
KEYTRUDA 10 mg/kg (HR, 0.48 [95% CI, 0.35-0.66]; p<0.00001), and
24 percent with docetaxel. In this group, median OS was 15.8 months
with KEYTRUDA 2 mg/kg, 18.8 months with KEYTRUDA 10 mg/kg, and 8.2
months with docetaxel. ORR was 29 percent (95% CI, 22-38,
p<0.00001) with KEYTRUDA 2 mg/kg, 32 percent (95% CI, 24-40,
p<0.00001) with KEYTRUDA 10 mg/kg, and nine percent (95% CI,
5-14) with docetaxel. Responses to KEYTRUDA continued to be
durable; among patients with high levels of PD-L1 expression who
responded to treatment, 68 and 63 percent on the KEYTRUDA 2 mg/kg
and 10 mg/kg treatment arms, respectively, were alive,
progression-free, and had not received additional therapy for their
disease, compared to 15 percent in the docetaxel treatment arm.
The safety profile of KEYTRUDA was consistent with that observed
in previously reported studies of KEYTRUDA. Treatment-related
adverse events remained lower with KEYTRUDA compared to docetaxel.
Among the total study population, 13, 17, and 36 percent of
patients experienced Grades 3-5 treatment-related adverse events
with KEYTRUDA (pembrolizumab) 2 mg/kg, KEYTRUDA 10 mg/kg, and
docetaxel, respectively. Compared with the previous analysis, two
additional patients in the KEYTRUDA 2 mg/kg arm and five patients
in the KEYTRUDA 10 mg/kg arm experienced immune-mediated adverse
events, none of which led to death. Grade 3-5 immune-mediated
adverse events that occurred in two or more patients included
pneumonitis (n=14), severe skin toxicities (n=8), and colitis
(n=4). Additional immune-mediated adverse events observed in at
least two patients in the KEYTRUDA arms of the study included
hypothyroidism, hyperthyroidism, pancreatitis, adrenal
insufficiency, myositis, thyroiditis, hepatitis, hypophysitis, and
type 1 diabetes mellitus. In this study to date, there have been 10
treatment-related adverse events that led to death, two with
KEYTRUDA 2 mg/kg, three with KEYTRUDA 10 mg/kg, and five with
docetaxel.
These data will be presented in a poster discussion session on
Oct. 9 from 2:45 – 4:15 p.m. CEST (Abstract #LBA48) (Location:
Oslo).
Patient-Reported Outcomes Findings from KEYNOTE-010 (Abstract
#1219P)
Also reported at the ESMO 2016 Congress were health-related
quality of life (HRQoL) outcomes from the KEYNOTE-010 trial.
Findings were based on patient-reported assessments using the
European Organization for Research and Treatment of Cancer Quality
of Life Questionnaire Core 30 (EORTC QLQ-C30), EORTC QLQ Lung
Cancer 13, and EuroQol-5D-3L instruments to measure for outcomes
such as physical, role, emotional, cognitive, and social
functioning, as well as lung cancer and treatment-related symptoms,
among other measures.
Overall, from baseline to the 12-week assessment, patients
treated with KEYTRUDA (2 mg/kg or 10 mg/kg every three weeks)
reported numeric improvements, some of which were significant, in
HRQoL and prolonged time to deterioration of lung cancer symptoms
(defined using a composite endpoint of cough, dyspnea, and chest
pain) compared with docetaxel (75 mg/m2 every three
weeks).
These findings, along with results from additional
patient-reported outcomes analyses, suggest that HRQoL and symptoms
were maintained or improved more with KEYTRUDA than with
docetaxel.
These data were presented in a poster session on Oct. 8 from 1 –
2 p.m. CEST (Location: Hall E).
PD-L1 Prevalence Findings from KEYNOTE-001, -010, and -024
(Abstract #1060P)
Results from a third NSCLC abstract at the ESMO 2016 Congress
explored, for the first time, the prevalence of PD-L1 in patients
screened across multiple studies. The analysis assessed 4,784
patients with NSCLC who had tumors evaluable for PD-L1 expression
and were screened for eligibility in three registrational studies
of KEYTRUDA (pembrolizumab) – KEYNOTE-001, KEYNOTE-010, and
KEYNOTE-024. Based on this pooled analysis, 66 percent of patients
across all three trials were determined to express PD-L1 (TPS of
one percent or more) and 28 percent were determined to have high
levels of PD-L1 expression (TPS of 50 percent or more). These
findings were similar across demographic and disease
characteristics examined, including prior lines of therapy, age,
tumor source (primary and metastases), and histology (squamous and
non-squamous).
These data will be presented in a poster session on Oct. 9 from
1 – 2 p.m. CEST (Location: Hall E).
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
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. 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 (pembrolizumab) 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 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
(pembrolizumab) 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 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
(pembrolizumab).
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%).
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 350 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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