18.5 Percent Overall Response Rate Observed
in KEYTRUDA-Treated Patients with This Aggressive Form of Breast
Cancer
Phase 2 Study Planned for the First Half of
2015 (KEYNOTE-086)
Merck (NYSE: MRK), known as MSD outside the United States and
Canada, announced today early study findings demonstrating an
overall response rate of 18.5 percent with KEYTRUDA, the company’s
anti-PD-1 therapy, as assessed by RECIST v1.1, central review
(n=5/27), in PD-L1 positive, advanced triple-negative breast cancer
– one of the most aggressive forms of breast cancer. At the time of
analysis, the median duration of response had not been reached with
three of five responders on therapy for 11 months or more (range,
15 to 40+ weeks). These early findings, from the ongoing Phase 1b
KEYNOTE-012 study, were shared today for the first time as part of
the official press program at the 2014 San Antonio Breast Cancer
Symposium (SABCS) (ABSTRACT #S1-09) and will be presented in an
oral session at 10:45 a.m. CST by Dr. Rita Nanda, the University of
Chicago.
“Metastatic, triple-negative breast cancer is an aggressive and
often difficult to treat disease,” said Dr. Rita Nanda, associate
director, breast medical oncology, the University of Chicago and
principal investigator for the KEYTRUDA triple-negative breast
cancer Phase 1b study cohort. “The results presented at this year’s
SABCS, while early, show encouraging anti-tumor activity in these
patients, most of whom had received multiple prior
chemotherapies.”
“This year, Merck has significantly advanced our immuno-oncology
development program and new data for KEYTRUDA have been presented
in seven different cancers, including these first findings in
triple-negative breast cancer,” said Dr. Alise Reicin, vice
president, global clinical development, oncology, Merck Research
Laboratories. “These early data with KEYTRUDA show responses in
patients with one of the most aggressive forms of breast cancer and
further our understanding of the PD-1 pathway’s role in this
disease. Our Phase 2 study planned for the first half of 2015 will
be an important next step for our breast cancer clinical
program.”
Early Findings Evaluating KEYTRUDA in Advanced
Triple-Negative Breast Cancer
Data presented were from a cohort of the ongoing Phase 1b
KEYNOTE-012 study which evaluated KEYTRUDA monotherapy at 10 mg/kg
every two weeks in patients with advanced TNBC whose tumors were
determined to be positive for PD-L1 expression (n=32). As measured
by Merck’s proprietary PD-L1 immunohistochemistry (IHC) clinical
trial assay, tumors were considered to be PD-L1 positive if
staining was present in the stroma or in greater than or equal to
one percent of tumor cells. In the study, 58 percent of patients
screened had tumors determined to be positive for PD-L1 expression.
Most patients enrolled in this study had received two or more prior
chemotherapies for metastatic disease and 87.5 percent had received
prior neo-adjuvant or adjuvant therapy.
Antitumor Activity with KEYTRUDA by Response
Evaluation Criteria in Solid Tumors (RECIST) v1.1, Central
Review*
Patients Evaluable for Response
(n=27)(a)
Overall Response Rate (ORR), n
(%)
5 (18.5%)
Best Overall Response, n (%)
Complete Responseb
1 (3.7%)
Partial Responseb
4 (14.8%)
Stable Disease
7 (25.9%)
Progressive Disease
12 (44.4%)
No Assessmentc
3 (11.1%) *Analysis cut-off as of: November 10, 2014.
aIncludes patients with measurable disease
at baseline who received ≥1 pembrolizumab dose and who had ≥1
post-baseline scan or discontinued therapy before the first scan
due to progressive disease or a treatment-related AE. Five patients
were excluded because they did not have any assessments per central
review (n=2) or because they did not have measurable disease per
central review at baseline (n=3).
bConfirmed responses only.
c“No assessment” signifies patients who
discontinued therapy before the first post-baseline scan due to
progressive disease or a treatment-related AE.
The median time to response was 18 weeks (range, 7-32 weeks). In
the study, 33 percent of patients with KEYTRUDA achieved tumor
shrinkage. At six months, the progression-free survival rate with
KEYTRUDA was 23.3 percent.
Adverse events were consistent with previously reported safety
data for KEYTRUDA. The most common treatment-related adverse events
(occurring in greater than or equal to five percent of patients)
included arthralgia (n=6), fatigue (n=6), myalgia (n=5), nausea
(n=5), ALT increased (n=2), AST increased (n=2), diarrhea (n=2),
erythema (n=2) and headache (n=2). Grade 3-5 treatment-related
adverse events occurred in a total of five patients and included
anemia, disseminated intravascular coagulation (DIC), headache,
meningitis aseptic, decreased blood fibrinogen, and pyrexia. Two
patients discontinued KEYTRUDA due to adverse events. One
treatment-related death was reported in a patient with rapidly
progressive disease and was due to DIC with thrombocytopenia and
decreased blood fibrinogen.
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 assessed by
independent radiology review) in PD-L1 positive tumors; secondary
endpoints include progression-free survival (PFS), overall survival
(OS) and duration of response. In 2014, early findings were
presented for all four cohorts of the Phase 1b KEYNOTE-012
study.
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.
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.
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.
Other clinically important immune-mediated adverse reactions can
occur. 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.
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 of the adverse
reaction to Grade 1 or less, initiate corticosteroid taper and
continue to taper over at least 1 month. Restart KEYTRUDA if the
adverse reaction remains at Grade 1 or less. Permanently
discontinue KEYTRUDA for any severe or Grade 3 immune-mediated
adverse reaction that recurs and for any life-threatening
immune-mediated adverse reaction.
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 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.
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. 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 Breast Cancer
Breast cancer is a malignant tumor that begins in the cells of
the breast.1 Worldwide, breast cancer is most common cancer among
women, with an estimated 1.67 million new cases diagnosed in 2012.2
Breast cancer ranks as the fifth most common cause of cancer death
worldwide.2 Triple-negative breast cancer (TNBC) is an aggressive
type of breast cancer where the cancer cells do not have estrogen
or progesterone receptors and do not have too much HER2, a
growth-promoting protein.3 Approximately 15 to 20 percent of breast
cancer patients are diagnosed with triple-negative breast
cancer.4
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 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 YouTube.
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
legislation in the United States and internationally; global trends
toward healthcare cost containment; technological advances, new
products and patents attained by competitors; challenges inherent
in new product development, including obtaining regulatory
approval; Merck’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 Merck’s patents and other
protections for innovative products; and the exposure to
litigation, including patent litigation, and/or regulatory
actions.
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).
KEYTRUDA® is a registered trademark of Merck
& Co., Inc., Whitehouse Station, N.J., USA
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.
1 American Cancer Society. Breast Cancer. Available at:
http://www.cancer.org/acs/groups/cid/documents/webcontent/003090-pdf.pdf.
Accessibility verified on December 9, 2014. 2 GLOBOCAN. Breast
Cancer: Estimated Incidence, Mortality and Prevalence Worldwide in
2012. Available at:
http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx.
Accessibility verified on December 9, 2014. 3 American Cancer
Society. How is breast cancer classified? Available at:
http://www.cancer.org/cancer/breastcancer/detailedguide/breast-cancer-classifying.
Accessibility verified on December 9, 2014. 4 Li CI et al. J
Clin Oncol 2003;21:28-34
MerckMedia:Pamela Eisele, (267) 305-3558Claire Mulhearn, (908)
236-1118orInvestor:Joseph Romanelli, (908) 740-1986Justin Holko,
(908) 740-1879
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