Data Investigating KEYTRUDA® (pembrolizumab), Merck’s Anti-PD-1 Therapy, in Patients with Advanced Triple-Negative Breast Cancer Presented at 2014 San Antonio Breast Cancer Symposium


December 10, 2014 8:30 am ET

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)

SAN ANTONIO–(BUSINESS WIRE)–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

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


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

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

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

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,

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,
and connect with us on Twitter,
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 (

KEYTRUDA® is a registered trademark of Merck
& Co., Inc., Whitehouse Station, N.J., USA

Please see Prescribing Information for KEYTRUDA (pembrolizumab) at
and the Medication Guide for KEYTRUDA at

1 American Cancer Society. Breast Cancer. Available at:
Accessibility verified on December 9, 2014. 
GLOBOCAN. Breast Cancer: Estimated Incidence, Mortality and Prevalence
Worldwide in 2012. Available at:
Accessibility verified on December 9, 2014. 
American Cancer Society. How is breast cancer classified? Available at:
Accessibility verified on December 9, 2014. 
4 Li
CI et al. J Clin Oncol 2003;21:28-34

Pamela Eisele, (267) 305-3558
Claire Mulhearn, (908) 236-1118
Joseph Romanelli, (908) 740-1986
Justin Holko, (908) 740-1879

Unsubscribe from email alerts