Collaborative Trial is First to Investigate
an Anti-PD-1 Therapy, Pembrolizumab, Combined with
Trastuzumab
Study to Explore Whether New Approach May
Reverse Trastuzumab Resistance in Cancer with Significant Unmet
Need
The International Breast Cancer Study Group (IBCSG), Breast
International Group (BIG), and Merck, known as MSD outside the
United States and Canada, today announced the opening of the
PANACEA study, a global collaborative study exploring a new way to
treat HER2+ breast cancer that has become resistant to the current
standard of care. The PANACEA study will investigate the use of
pembrolizumab (KEYTRUDA®) in combination with trastuzumab to
evaluate whether the addition of an anti-PD-1 therapy can reverse
trastuzumab resistance in patients with HER2+ breast cancer whose
cancer has spread while on trastuzumab therapy.
Worldwide, breast cancer is the most common cancer among women.1
About one in five patients with breast cancer have too much of a
growth-promoting protein known as HER2/neu (or just HER2) on the
surface of cancer cells. Breast cancers with too much of this
protein tend to grow and spread more aggressively.
“PANACEA is the first phase 2 immunotherapy trial not only in
HER2+ breast cancer, but in the entire breast cancer field,” said
Sherene Loi, MD, PhD, study chair, division of cancer medicine,
Peter MacCallum Cancer Centre, Australia. “If successful, this may
herald a new treatment approach in certain types of breast
cancer.”
“Traditionally, breast cancer has not been thought as an
‘immunogenic’ solid tumor, which is why immunotherapies have been
initially evaluated in melanoma and renal cancers,” said Fabrice
André, MD, PhD, study co-chair, department of medical oncology,
Institut Gustave Roussy, France. “However, a significant amount of
preclinical and correlative clinical data suggest that HER2+ breast
cancer could be amenable to immuno-therapeutic approaches. That’s
what the many centers involved in this worldwide collaborative
study will try to prove in the next couple of years.”
“Merck is committing its resources to advance the science of
immuno-oncology, so we can better understand the role of the PD-1
and other immune pathways in the treatment of breast and other
cancers,” said Alise Reicin, MD, vice president, global clinical
development, oncology, Merck Research Laboratories. “This study
will provide insight into the role of the PD-1/PD-L1 pathway in
HER2+ breast cancer, and we are very pleased to be collaborating
with IBCSG and BIG on the PANACEA study.”
About PANACEA Study
The trial, “Anti-PD-1 Monoclonal Antibody in Advanced,
Trastuzumab-resistant, HER2+ Breast Cancer (PANACEA),” is a Phase
1b/2 study in patients with HER2+ breast cancer whose cancer has
spread while on treatment with trastuzumab. Primary outcome
measures of the study are recommended dose and efficacy and safety
profile of pembrolizumab in combination with trastuzumab. Response
will be assessed by RECIST 1.1 criteria. Secondary outcome measures
include safety and tolerability, disease control, duration of
response, time to progression, progression-free survival and
overall survival.
The study is enrolling adult females with unresectable or
metastatic breast adenocarcinoma with confirmed HER2-positivity.
There are 10 sites participating in the study across Europe and
Australia: Peter MacCallum Cancer Centre and Westmead Hospital in
Australia; Medical University of Vienna in Austria; Jules Bordet
Institute and CHU Sart Tilman in Belgium; Institut de Cancérologie
de l’OUEST, Centre Léon Bérard and Institut Gustave Roussy in
France; and Istituto Europeo di Oncologia Milano and Azienda USL4
Prato in Italy.
For more information on the PANACEA study, including how to
enroll, please visit:
http://clinicaltrials.gov/ct2/show/NCT02129556?term=pembrolizumab+AND+breast&rank=1.
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 the International Breast Cancer Study Group
(IBCSG)
The International Breast Cancer Study Group is a non-profit
research organization dedicated to innovative clinical research
designed to improve the prognosis of women with breast cancer.
Formed in 1977 as the Ludwig Breast Cancer Study Group, IBCSG
strives to conduct clinical trials at the highest level of
knowledge in breast cancer medicine, trial methodology, data
handling, and ethical conduct. Patients and investigators from six
continents (Europe, Australia/New Zealand, Africa, Asia, North and
South America) cooperate by participating in extensive clinical
trials in breast cancer populations, guided by the highest
scientific and ethical standards. IBCSG plays a key role in
disseminating practice-changing trial results to the breast cancer
community. For more information, visit www.ibcsg.org.
About Breast International Group (BIG)
The Breast International Group (BIG) is a non-profit
organization for academic breast cancer research groups from around
the world, based in Brussels, Belgium.
Founded by leading European opinion leaders in 1999, BIG now
constitutes a network of 55 collaborative groups from Europe,
Canada, Latin America, Asia and Australasia. These entities are
tied to several thousand specialized hospitals and research centers
worldwide. More than 30 clinical trials are run or are under
development under the BIG umbrella at any one time. BIG also works
closely with the US National Cancer Institute (NCI) and the North
American Breast Cancer Groups (NABCG), so that together they act as
a strong integrating force in the breast cancer research arena.
To make significant scientific advances in breast cancer
research, reduce unnecessary duplication of effort, and optimally
serve those affected by the disease, global collaboration is
crucial. Therefore BIG facilitates breast cancer research at
international level, by stimulating cooperation between its members
and other academic networks, and collaborating with, but working
independently from, the pharmaceutical
industry.www.BIGagainstbreastcancer.org
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.
Merck’s 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.
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).
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
& Co., Inc., Whitehouse Station, N.J., USA
1 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.
Photos/Multimedia Gallery Available:
http://www.businesswire.com/multimedia/home/20141210005070/en/
International Breast Cancer Study GroupLaura Cava Northrop,
617-632-3973press@ibcsg.orgorBreast International GroupCecilia
Waldvogel, +41 79
478-0238cecilia.waldvogel@BIGagainstbc.orgorMerckClaire Mulhearn,
908-236-1118claire.mulhearn@merck.com
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