Merck and NanoString Announce Clinical Research Collaboration to Develop an Immune-Related Gene Expression Assay for Use in the Development Program for KEYTRUDA® (pembrolizumab)
May 28, 2015 7:30 am ET
Collaboration Builds on Merck’s R&D and NanoString’s Biomarker Development Leadership Positions in Immuno-Oncology
Early Data Evaluating Immune-Related Signatures with KEYTRUDA in Multiple Cancers to be Presented for the First Time at 2015 ASCO Annual Meeting
KENILWORTH, N.J. & SEATTLE–(BUSINESS WIRE)–Merck (NYSE:MRK), known as MSD outside the United States and Canada, and
NanoString Technologies, Inc. (NASDAQ:NSTG) today announced a clinical
research collaboration to develop an assay that will optimize
immune-related gene expression signatures and evaluate the potential to
predict benefit from Merck’s anti-PD-1 therapy, KEYTRUDA®
(pembrolizumab), in multiple tumor types. The collaboration between
NanoString Technologies, Inc., a provider of life science tools for
translational research and molecular diagnostic products, and Merck,
through a subsidiary, will utilize NanoString’s nCounter®
Analysis System to optimize gene expression signatures as part of the
clinical development program for KEYTRUDA.
“Our commitment to advancing the science of immuno-oncology includes
pursuing cutting-edge RNA and DNA approaches to identify a range of
biomarkers, such as immune-related gene expression signatures, that in
addition to PD-L1 expression, may help to identify patients who may be
more likely to experience improved benefit with KEYTRUDA,” said Dr. Eric
Rubin, vice president and therapeutic area head, oncology early-stage
development, Merck Research Laboratories. “Our collaboration with
NanoString Technologies is an important advancement for our early-stage,
immuno-oncology development program. Early data exploring the predictive
value of the NanoString-derived gene expression signatures with KEYTRUDA
will be presented at ASCO 2015.”
“We are excited to work with Merck to help direct treatment with
KEYTRUDA,” said Brad Gray, president and chief executive officer of
NanoString Technologies. “New approaches in immuno-oncology, like
KEYTRUDA, have the potential to transform cancer care across many
different tumor types. With our nCounter technology and in vitro diagnostic
capability, NanoString is ideally positioned to address the critical
challenge of matching patients to powerful new therapies. This
collaboration with Merck complements our existing relationships with MD
Anderson and the Cancer Immunotherapy Trials Network, and builds on our
leadership position in immuno-oncology biomarker development.”
Early Data on Immune-based Gene Expression Signatures at 2015 ASCO
Annual Meeting
First-time presentations of data evaluating immune-based gene expression
signatures developed using NanoString’s nCounter® Analysis
System, and their correlation to patient benefit with KEYTRUDA will be
presented at this year’s 51st Annual Meeting of the American
Society of Clinical Oncology (May 29-June 2, 2015 in Chicago). The early
data to be presented include findings in bladder cancer (Abstract
#4502), advanced melanoma (Abstract #3001), gastric cancer (Abstract
#3026), and head and neck cancer (Abstract #6017). These early data are
based on an initial signature, the interferon-gamma response gene, which
was derived from initial findings that expression of this immune
response gene predicted response to KEYTRUDA in advanced melanoma
patients. Additional signatures are in development based on extension of
these initial findings.
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
administered as an intravenous infusion over 30 minutes 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 a broad and fast-growing clinical development program
for KEYTRUDA with more than 100 clinical trials – across more than 30
tumor types and enrolling more than 16,000 patients – both as a
monotherapy and in combination with other therapies.
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 NanoString Technologies, Inc.
NanoString Technologies provides life science tools for translational
research and molecular diagnostic products. The company’s nCounter
Analysis System has been employed in life sciences research since it was
first introduced in 2008 and has been cited in over 700 peer-reviewed
publications. The nCounter Analysis System offers a cost-effective way
to easily profile the expression of hundreds of genes, proteins, miRNAs,
or copy number variations, simultaneously with high sensitivity and
precision, facilitating a wide variety of basic research and
translational medicine applications, including biomarker discovery and
validation. The company’s technology has also been applied to diagnostic
use. The Prosigna Breast Cancer Prognostic Gene Signature Assay together
with the nCounter Dx Analysis System is FDA 510(k) cleared for use as a
prognostic indicator for distant recurrence of breast cancer. For more
information, please visit www.nanostring.com.
NanoString Technologies, Inc. Forward-Looking Statement
This press release contains forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995,
including statements regarding the likelihood of this collaboration to
translate genomic discoveries to diagnostic assays, and the potential to
develop diagnostic assays on the nCounter platform that will predict
response to KEYTRUDA and other anti-PD-1 therapies. Forward-looking
statements are subject to risks and uncertainties that could cause
actual results to differ materially and reported results should not be
considered as an indication of future performance. These risks and
uncertainties include, but are not limited to: risks associated with
keeping pace with rapidly changing technology and customer requirements;
risks regarding the company’s ability to successfully introduce new
products; risks that new market opportunities may not develop as quickly
as expected; risks associated with competition in marketing and selling
products; risks of increased regulatory requirements; as well as the
other risks set forth in the company’s filings with the Securities and
Exchange Commission. These forward-looking statements speak only as of
the date hereof. NanoString Technologies disclaims any obligation to
update these forward-looking statements.
The NanoString Technologies logo, NanoString, NanoString Technologies,
nCounter and Prosigna are either registered trademarks or trademarks
of NanoString Technologies, Inc.
Merck’s 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 healthcare leader working to help the world be
well. Merck is known as MSD outside of 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 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 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 (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
Merck Media Relations:
Pamela Eisele, 267-305-3558
Claire Mulhearn, 908-236-1118
or
Merck Investor Relations:
Justin Holko, 908-740-1879
or
NanoString Investor/Media Relations:
Leigh Salvo, 415-513-1281
