Merck and Dynavax Announce New Collaboration Investigating the Combination of Immuno-Oncology Therapies


June 1, 2015 7:30 am ET

Studies to Evaluate the Combination of Dynavax’s SD-101 with Two Immunotherapies from Merck’s Pipeline, KEYTRUDA® (pembrolizumab) and MK-1966

Collaboration Includes First-in-human Study for MK-1966, a New Investigational Anti-interleukin-10 (anti-IL-10) Immunomodulator from Merck’s Rapidly Growing Immuno-oncology Pipeline

KENILWORTH, N.J. & BERKELEY, Calif.–(BUSINESS WIRE)–Merck (NYSE:MRK), known as MSD outside the United States and Canada, and
Dynavax Technologies Corporation (Nasdaq: DVAX) today announced they
have entered into two clinical trial collaboration agreements to
investigate the potential synergistic effect of combining
immunotherapies from both companies’ pipelines: Merck’s anti-PD-1
therapy, KEYTRUDA® (pembrolizumab), and its investigational
anti-interleukin-10 (anti-IL-10) immunomodulator, MK-1966, with
Dynavax’s investigational toll-like receptor 9 (TLR9) agonist, SD-101.

SD-101, KEYTRUDA, and MK-1966 are immunotherapies designed to enhance
the body’s own defenses in fighting cancer. SD-101 is designed to
mediate anti-tumor effects by triggering both innate and adaptive immune
responses, including the induction of high levels of Type 1 interferon
to stimulate recruitment of T-cells. KEYTRUDA is a humanized monoclonal
antibody that blocks the interaction between PD-1 (programmed death
receptor-1) and its ligands, PD-L1 and PD-L2. MK-1966 is an
investigational anti-IL-10 immunomodulator designed to neutralize the
immune-suppressive environment for tumors. The collaboration includes
multiple studies that will evaluate:

  • Safety and efficacy of combining SD-101 with KEYTRUDA in
    patients with advanced melanoma; this Phase 1b/2, multicenter,
    open-label study is expected to be initiated in the second half of
  • Safety and efficacy of combining SD-101 with MK-1966 in patients with
    solid or hematological malignancies; this Phase 1 study is expected to
    be initiated in the second half of 2015.

“The collaboration with Dynavax is rooted in Merck’s commitment to
advancing breakthrough science in the field of immuno-oncology in order
to address the complex interplay between the immune system and cancer,”
said Dr. Eric Rubin, vice president and therapeutic area head, oncology
early stage development, Merck Research Laboratories. “We are pleased
that this latest collaboration not only investigates the potential of
KEYTRUDA as a combination therapy, but also includes our new
immunomodulator candidate, MK-1966.”

“Our interest in working with Merck on these clinical collaborations was
propelled by the synergistic activity we have seen when SD-101 is
combined with checkpoint inhibitors in preclinical models,” said Eddie
Gray, chief executive officer of Dynavax. “These collaborations with
Merck will facilitate our objective to demonstrate SD-101’s potential to
complement multiple therapeutic modalities and thereby provide benefit
to patients.”

Under the terms of the agreement, Dynavax will sponsor and fund the
SD-101 and KEYTRUDA study. Merck will sponsor and fund the SD-101 and
MK-1966 study. The agreements include provisions where the parties may
agree to extend either collaboration to include a Phase 3 clinical
trial. Additional details of the agreements between Dynavax and Merck,
through a subsidiary, were not disclosed.

About SD-101

SD-101 is a proprietary, second-generation, TLR9 agonist CpG-C class
oligodeoxynucleotide. SD-101 activates multiple anti-tumor activities of
innate immune cells and activates plasmacytoid dendritic cells to
stimulate T cells specific for antigens released from dying tumor cells.
TLR9 agonists such as SD-101 enhance T and B cell responses and provide
potent Type 1 interferon induction and maturation of plasmacytoid
dendritic cells to antigen-presenting cells. SD-101 is being evaluated
in several Phase 1/2 oncology studies to assess its preliminary safety
and activity.

About MK-1966

MK-1966, an investigational anti-interleukin-10 (anti-IL-10)
immunomodulator, is designed to neutralize the immune-suppressive
environment for tumors. MK-1966 blocks the activity of IL-10 which is
known to down modulate the immune activation that is needed to kill
tumor cells in the tumor microenvironment. These effects include
decrease in cytokine production, upregulation of T regulatory cell
activity and downregulation of antigen presenting cell activity. Based
on preclinical data, co-administration of an anti-IL-10 with a TLR9
agonist may provide clinical benefit in the treatment of certain cancers.

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

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 Dynavax

Dynavax, a clinical-stage biopharmaceutical company, discovers and
develops novel vaccines and therapeutics in the areas of infectious and
inflammatory diseases and oncology. Dynavax’s lead product candidates
are HEPLISAV-B™, a Phase 3 investigational adult hepatitis B vaccine and
SD-101, an investigational cancer immunotherapeutic currently in several
Phase 1/2 studies. For more information visit

Dynavax Forward Looking Statements

This press release contains “forward-looking” statements, including
expectations for the conduct and timing of clinical trials of SD-101.
Actual results may differ materially from those set forth in this press
release due to the risks and uncertainties inherent in our business,
including whether we can timely provide adequate clinical supplies,
initiate one or more studies, enroll a sufficient number of subjects and
ultimately complete any study, and whether or not the parties may reach
any future agreement on further studies or a more extensive
collaboration beyond the clinical trials contemplated under the existing
agreements, as well as other risks detailed in the “Risk Factors”
section of our current periodic reports with the SEC. We undertake no
obligation to revise or update information herein to reflect events or
circumstances in the future, even if new information becomes available.
Information on Dynavax’s website at is
not incorporated by reference in our current periodic reports with
the SEC.

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,

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,
and connect with us on Twitter,
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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 (

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

Merck Media Relations:
Pamela Eisele, 267-664-0282
Claire Mulhearn, 908-200-1889
Merck Investor Relations:
Justin Holko, 908-740-1879
Dynavax Investor/Media Relations:
Michael Ostrach, 510-665-7257

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