WALTHAM, Mass. and KENILWORTH, N.J., Sept.
28, 2015 /PRNewswire/ -- Syndax Pharmaceuticals, Inc.
and Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced the dosing of the
first patients in the Phase 1b/2 clinical trial of Syndax's
entinostat in combination with Merck's anti-PD-1 therapy
KEYTRUDA® (pembrolizumab) in patients with non-small
cell lung cancer (NSCLC) or melanoma. The clinical trial,
designated ENCORE 601 by Syndax and KEYNOTE 142 by Merck, is
evaluating the safety, tolerability and efficacy of entinostat, an
oral, small molecule that targets immune regulatory cells, combined
with KEYTRUDA, an anti-programmed cell death protein 1 (anti-PD-1)
antibody.
"This is an important clinical milestone for Syndax and our
collaboration with Merck that was achieved on schedule with our
joint development plan," said Michael L.
Meyers, M.D., Ph.D., Syndax's Chief Development Officer. "As
entinostat has been shown in preclinical models to reduce the
number and inhibit the function of host immune suppressor cells, we
believe that entinostat combined with KEYTRUDA could result in an
improved response rate for the combination compared to either agent
alone. The initiation of this trial advances our immuno-oncology
program developing entinostat as a potential combination therapy in
multiple cancer indications with an initial focus on tumors that
have shown sensitivity to immunotherapy."
"Our collaboration with Syndax exemplifies our interest in
exploring innovative therapeutic combinations with KEYTRUDA," said
Eric Rubin, M.D., vice president and
therapeutic area head, early-stage oncology development, Merck
Research Laboratories. "We are pleased with the rapid initiation
and progress being made by Syndax towards gaining a better
understanding of the potential of KEYTRUDA and entinostat in these
difficult-to-treat patient populations."
The ENCORE 601/KEYNOTE 142 trial is designed as a Phase 1b/2
open label clinical trial with dose escalation for entinostat, in
which the Phase 1b portion will evaluate the safety and
tolerability of the combination of entinostat and KEYTRUDA in
patients with NSCLC, and the Phase 2 portion will assess the safety
and preliminary efficacy of the combination in separate cohorts in
patients with NSCLC or melanoma. The trial will be conducted in
the United States and is expected
to enroll up to 178 patients.
About KEYTRUDA® (pembrolizumab)
KEYTRUDA 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 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, including
Grade 2 or 3 cases in 8 (1.9%) and 1 (0.2%) patients, respectively,
receiving KEYTRUDA. 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 patients for signs and symptoms of
hypophysitis (including hypopituitarism and adrenal insufficiency).
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.
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.
Type 1 diabetes mellitus, including diabetic ketoacidosis, has
occurred in patients receiving KEYTRUDA. Monitor patients for
hyperglycemia and other signs and symptoms of diabetes. Administer
insulin for type 1 diabetes, and withhold KEYTRUDA in cases of
severe hyperglycemia until metabolic control is achieved.
Nephritis occurred in 3 (0.7%) patients, 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.
Other clinically important immune-mediated adverse reactions can
occur. The following clinically significant immune-mediated adverse
reactions occurred in patients treated with KEYTRUDA: exfoliative
dermatitis, uveitis, arthritis, myositis, pancreatitis, hemolytic
anemia, partial seizures arising in a patient with inflammatory
foci in brain parenchyma, severe dermatitis including bullous
pemphigoid, 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.
Infusion-related reactions, including severe and
life-threatening reactions, have occurred in patients receiving
KEYTRUDA. Monitor patients for signs and symptoms of
infusion-related reactions including rigors, chills, wheezing,
pruritus, flushing, rash, hypotension, hypoxemia, and fever. For
severe or life-threatening reactions, stop infusion and permanently
discontinue KEYTRUDA.
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.
KEYTRUDA was discontinued for adverse reactions in 9% of 411
patients. Adverse reactions, reported in at least two patients,
that led to discontinuation of KEYTRUDA were: pneumonitis, renal
failure, and pain. Serious adverse reactions occurred in 36% of
patients. The most frequent serious adverse reactions, reported in
2% or more of patients, were renal failure, dyspnea, pneumonia, and
cellulitis.
The most common adverse reactions (reported in at least 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 Syndax Pharmaceuticals, Inc.
Syndax is a clinical stage biopharmaceutical company developing
entinostat as a combination therapy in multiple cancer indications
with an initial focus on tumors that have shown sensitivity to
immunotherapy, including lung cancer, melanoma and triple-negative
breast cancer (TNBC). Entinostat is an oral, small molecule drug
candidate that has direct effects on both cancer cells and immune
regulatory cells, potentially enhancing the body's immune response
to tumors. Entinostat is being evaluated as a combination
therapeutic in Phase 1b/2 clinical trials with Merck for non-small
cell lung cancer and melanoma and with Genentech for TNBC, as well
as in a Phase 3 clinical trial with ECOG-ACRIN for advanced hormone
receptor positive breast cancer. For more information on Syndax
please visit www.syndax.com.
Syndax's Cautionary Note on Forward-Looking
Statements
This press release contains forward-looking statements.
Forward-looking statements contained in this press release include,
without limitation, statements regarding Syndax's expectations
regarding the results of the Phase 1b/2 clinical trial combining
entinostat and KEYTRUDA, the development of its immuno-oncology
program, its belief that the Phase 1b/2 clinical trial combining
entinostat and KEYTRUDA advances its immuno-oncology program
developing entinostat as a potential combination therapy in
multiple cancer indications and the expected enrollment in this
trial. Words such as "may," "believe," "will," "expect," "plan,"
"anticipate," "estimate," "intend" and similar expressions (as well
as other words or expressions referencing future events, conditions
or circumstances) are intended to identify forward-looking
statements. These forward-looking statements are not guarantees of
future performance and involve a number of unknown risks,
assumptions, uncertainties and factors that are beyond Syndax's
control. All forward-looking statements are based on Syndax's
expectations and assumptions as of the date of this press release.
Actual results may differ materially from these forward-looking
statements. Except as required by law, Syndax expressly disclaims
any responsibility to update any forward-looking statement
contained herein, whether as a result of new information, future
events or otherwise.
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. For more information about our oncology clinical trials,
visit www.merck.com/clinicaltrials.
About Merck
Today's Merck is 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 and
YouTube.
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 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; 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 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 2014
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 at
http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdfand
the Medication Guide for KEYTRUDA at
http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf
Contacts
|
Merck Media
Relations:
|
Syndax Investor and
Media Relations:
|
Kim Hamilton: (908)
740-1863 Merck Investor Relations:
|
Karen L.
Bergman
BCC
Partners
(650) 575-1509,
kbergman@bccpartners.com
|
Teri Loxam: (908)
740-1986
Justin Holko: (908)
740-1879
|
Jen
LaVin
BCC
Partners
(207) 360-0473,
jlavin@bccpartners.com
|
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SOURCE Syndax Pharmaceuticals, Inc.