KEYTRUDA® monotherapy achieved 31
percent overall response rate in patients with PD-L1 positive,
advanced gastric cancer
Phase 2 study to be initiated in first
quarter of 2015 (KEYNOTE-059)
Merck (NYSE:MRK), known as MSD outside the United States and
Canada, today announced the first presentation of data on the
investigational use of KEYTRUDA® (pembrolizumab) – the company’s
anti-PD-1 therapy – in PD-L1 positive, advanced gastric cancer. The
early findings presented showed an overall response rate (confirmed
and unconfirmed) of 31 percent with KEYTRUDA as monotherapy, as
measured by investigator assessed, RECIST v1.1 (n= 12/39: 95% CI,
17-47). Similar overall response rates were observed in Asian
patients (a population with a high incidence of gastric cancer) and
non-Asian patients. At the time of analysis, response durations
ranged from 8+ to 20+ weeks with 11 of 12 responders continuing on
therapy.
These data, from a cohort of the ongoing Phase 1b KEYNOTE-012
study, were presented today, as part of a late-breaking oral
session, by Dr. Kei Muro, Aichi Cancer Center Hospital, Nagoya,
Japan, at the European Society for Medical Oncology (ESMO) 2014
Congress in Madrid, Spain (ABSTRACT #LBA15). Data investigating the
use of KEYTRUDA monotherapy in five tumor types will be presented
at ESMO 2014.
KEYTRUDA is indicated in the United States at a dose of 2 mg/kg
every three weeks for the treatment of patients with unresectable
or metastatic melanoma and disease progression following ipilimumab
and, if BRAF V600 mutation positive, a BRAF inhibitor. 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.
“Merck is advancing the development of KEYTRUDA across different
tumor types and lines of therapy,” said Dr. Alise Reicin, vice
president, oncology, Merck Research Laboratories. “We are
encouraged by the signals of anti-tumor activity in advanced
gastric cancer, and are eager to move ahead with the Phase 2 study
to better understand the potential of KEYTRUDA in advanced gastric
cancer.”
Early findings for investigational use of KEYTRUDA in
advanced gastric cancer
Data from a cohort of the ongoing Phase 1b KEYNOTE-012 study
evaluated KEYTRUDA monotherapy at 10 mg/kg every two weeks in
patients with advanced gastric cancer whose tumors were determined
to be positive for PD-L1 expression (n=39). As measured by Merck’s
proprietary immunohistochemistry (IHC) clinical trial assay, tumors
were classified as PD-L1 positive based on greater than or equal to
one percent of tumor cells demonstrating expression of the PD-L1
marker, or any positive staining with the same reagent in tumor
stroma. Enrollment was designed to include an equal number of Asian
and non-Asian patients. The majority of patients had received two
or more prior lines of therapy.
Antitumor activity by Response Evaluation Criteria in Solid
Tumors (RECIST) v1.1*
Total
n = 39
Non-Asian
n = 20
Asian
n = 19
Overall Response Rate (ORR), % (95% CI) 31 (17-47) 30 (12-54) 31
(12-56) Disease Control Rate (DCR), % (95% CI) 43 (28-60) 35
(15-59) 52 (29-75) Best overall response, n (%)
0 0 0
12 (31) 6 (30) 6 (32)
5 (13) 1 (5) 4 (21)
21 (54) 12 (60) 9 (47)
1 (2) 1 (5) 0
*Analysis cut-off date: August 6, 2014
Using a prototype assay for PD-L1 assessment, there was evidence
of a preliminary relationship between PD-L1 expression and ORR (P =
0.071)
In the study, tumor shrinkage was demonstrated in 41 percent of
evaluable patients who had measurable disease with one post
baseline scan, per RECIST v1.1 criteria.
Adverse events were consistent with previously reported safety
data for KEYTRUDA. The most common investigator-assessed,
treatment-related adverse events (occurring in greater than five
percent) included hypothyroidism (12.8%) and fatigue (12.8%). Grade
3-5 investigator-assessed, treatment-related adverse events
occurred in a total of three patients, with one patient each in
peripheral sensory neuropathy (Grade 3), hypoxia (Grade 5) and
pneumonitis (Grade 4). No infusion-related reactions were observed
and no patients discontinued KEYTRUDA due to a treatment-related
adverse reaction. One treatment-related death due to hypoxia, as
assessed by the investigator, was reported.
About the KEYNOTE-012 study
KEYNOTE-012 is an ongoing multi-center, non-randomized Phase 1b
trial evaluating the safety, tolerability, and anti-tumor activity
of KEYTRUDA monotherapy in patients with advanced triple negative
breast cancer (TNBC), advanced head and neck cancer, advanced
urothelial (bladder) cancer, or advanced gastric cancer. The
primary endpoints of the study include overall safety, tolerability
and anti-tumor activity (as measured by RECIST v1.1) in PD-L1
positive tumors; secondary endpoints include progression-free
survival (PFS), overall survival (OS) and duration of response.
Presentation of additional findings investigating the use of
KEYTRUDA in advanced non-small cell lung cancer (NSCLC)
Also presented today, were updated findings in patients with
treatment-naïve or previously treated advanced non-small cell lung
cancer (NSCLC) across cohorts from the ongoing Phase 1b KEYNOTE-001
study (Abstract #LBA43). Data presented in a late-breaking oral
session showed anti-tumor activity [overall response rate (ORR)]
with KEYTRUDA in both treatment-naïve and previously treated
patients with advanced NSCLC (n=236) of 26 and 20 percent,
respectively, across all doses and schedules assessed as measured
by independent central review, RECIST v1.1. Analysis by dose (2
mg/kg every three weeks, 10 mg/kg every three weeks, and 10 mg/kg
every two weeks) showed comparable ORR across dosing schedules (33
percent, 21 percent, and 21 percent, respectively).
About KEYTRUDA (pembrolizumab)
KEYTRUDA (pembrolizumab) is a humanized monoclonal antibody that
blocks the interaction between PD-1 and its ligands, PD-L1 and
PD-L2. By binding to the PD-1 receptor and blocking the interaction
with the receptor ligands, KEYTRUDA releases the PD-1
pathway-mediated inhibition of the immune response, including the
anti-tumor immune response.
Selected Important Safety Information for KEYTRUDA
Pneumonitis occurred in 12 (2.9%) of 411 patients with advanced
melanoma receiving KEYTRUDA (the approved indication in the United
States), including Grade 2 or 3 cases in 8 (1.9%) and 1 (0.2%)
patients, respectively. 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 pneumonitis.
Colitis (including microscopic colitis) occurred in 4 (1%) of
411 patients, including Grade 2 or 3 cases in 1 (0.2%) and 2 (0.5%)
patients respectively, 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.
Hepatitis (including autoimmune hepatitis) occurred in 2 (0.5%)
of 411 patients, including a Grade 4 case in 1 (0.2%) patient,
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 2 (0.5%) of 411 patients, including a
Grade 2 case in 1 and a Grade 4 case in 1 (0.2% each) patient,
receiving KEYTRUDA. Monitor for signs and symptoms of hypophysitis.
Administer corticosteroids for Grade 2 or greater hypophysitis.
Withhold KEYTRUDA for Grade 2; withhold or discontinue for Grade 3;
and permanently discontinue KEYTRUDA for Grade 4 hypophysitis.
Nephritis occurred in 3 (0.7%) patients receiving KEYTRUDA,
consisting of one case of Grade 2 autoimmune nephritis (0.2%) and
two cases of interstitial nephritis with renal failure (0.5%), one
Grade 3 and one Grade 4. 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.
Hyperthyroidism occurred in 5 (1.2%) of 411 patients, including
Grade 2 or 3 cases in 2 (0.5%) and 1 (0.2%) patients respectively,
receiving KEYTRUDA. Hypothyroidism occurred in 34 (8.3%) of 411
patients, including a Grade 3 case in 1 (0.2%) patient, receiving
KEYTRUDA. 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 corticosteroids for Grade 3 or greater
hyperthyroidism. Withhold KEYTRUDA for Grade 3; permanently
discontinue KEYTRUDA for Grade 4 hyperthyroidism. Isolated
hypothyroidism may be managed with replacement therapy without
treatment interruption and without corticosteroids.
The following clinically significant, immune-mediated adverse
reactions occurred in less than 1% of patients treated with
KEYTRUDA: exfoliative dermatitis, uveitis, arthritis, myositis,
pancreatitis, hemolytic anemia, partial seizures arising in a
patient with inflammatory foci in brain parenchyma, adrenal
insufficiency, myasthenic syndrome, optic neuritis, and
rhabdomyolysis.
Based on its mechanism of action, KEYTRUDA may 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 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.
For the treatment of advanced melanoma, KEYTRUDA was
discontinued for adverse reactions in 6% of 89 patients who
received the recommended dose of 2 mg/kg and 9% of 411 patients
across all doses studied. Serious adverse reactions occurred in 36%
of patients receiving KEYTRUDA (pembrolizumab). The most frequent
serious adverse drug reactions reported in 2% or more of patients
were renal failure, dyspnea, pneumonia, and cellulitis.
The most common adverse reactions (reported in ≥20% of patients)
were fatigue (47%), cough (30%), nausea (30%), pruritus (30%), rash
(29%), decreased appetite (26%), constipation (21%), arthralgia
(20%), and diarrhea (20%).
The recommended dose of KEYTRUDA is 2 mg/kg administered as an
intravenous infusion over 30 minutes every three weeks until
disease progression or unacceptable toxicity. 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. Safety and
effectiveness of KEYTRUDA have not been established in pediatric
patients.
About gastric cancer
Gastric cancer, also called stomach cancer, is a type of cancer
that begins in the stomach.1 Most gastric cancers are
adenocarcinomas, which develop from the cells of the innermost
lining (mucosa) of the stomach.1 Among others, risk factors for
gastric cancer include gender, age, ethnicity, geography and
bacterial infection with Helicobacter pylori.1 More than 70 percent
of gastric cancer cases occur in developing countries, with half of
all cases occurring in Eastern Asia (predominately China).2
Worldwide, gastric cancer is the fifth most common type of cancer
and the third leading cause of cancer death.2
Our focus on cancer
Our goal is to translate breakthrough science into biomedical
innovations to help people with cancer worldwide. For Merck
Oncology, helping people fight cancer is our passion, supporting
accessibility to our cancer medicines is our commitment, and
pursuing research in immuno-oncology is our focus to potentially
bring new hope to people with cancer. For more information about
our oncology clinical trials, visit
www.merck.com/clinicaltrials.
About Merck
Today's Merck is a global healthcare 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 consumer care 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 healthcare through far-reaching policies,
programs and partnerships. For more information, visit
www.merck.com and connect with us on Twitter, Facebook and
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Forward-Looking Statement
This news release includes “forward-looking statements” within
the meaning of the safe harbor provisions of the United States
Private Securities Litigation Reform Act of 1995. These statements
are based upon the current beliefs and expectations of Merck’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 healthcare
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toward healthcare cost containment; technological advances, new
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Merck 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 Merck’s 2013 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 the Medication Guide for KEYTRUDA at
http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf.
KEYTRUDA® is a registered trademark of Merck
Sharp & Dohme Corp., a subsidiary of Merck & Co.,
Inc.
1 American Cancer Society. Stomach Cancer.
http://www.cancer.org/acs/groups/cid/documents/webcontent/003141-pdf.pdf.
Accesses September 17, 2014.
2 World Health Organization. Globocan 2012 Stomach Cancer:
Estimated Incidence, Mortality and Prevalence Worldwide in 2012.
http://globocan.iarc.fr/old/FactSheets/cancers/stomach-new.asp.
Accessed September 17, 2014.
MerckMedia:Ian McConnell, 973-901-5722orClaire Mulhearn,
908-423-7425orInvestor:Joseph Romanelli, 908-423-5185orJustin
Holko, 908-423-5088
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