Merck and Moderna Announce Strategic Collaboration to Advance Novel mRNA-Based Personalized Cancer Vaccines with KEYTRUDA® (pembrolizumab) for the Treatment of Multiple Types of Cancer
June 29, 2016 6:00 am ET
Collaboration Combines Merck’s Leadership in Immuno-Oncology with Moderna’s Pioneering mRNA Vaccine Technology and Rapid Cycle Time, Small-Batch GMP Manufacturing Capabilities
KENILWORTH, N.J. & CAMBRIDGE, Mass.–(BUSINESS WIRE)–Merck (NYSE:MRK), known as MSD outside the United States and Canada, and
Moderna Therapeutics today announced a strategic collaboration and
license agreement to develop and commercialize novel messenger RNA
(mRNA)-based personalized cancer vaccines. The collaboration will
combine Merck’s established leadership in immuno-oncology with Moderna’s
pioneering mRNA vaccine technology and GMP manufacturing capabilities to
advance individually tailored cancer vaccines for patients across a
spectrum of cancers.
Moderna and Merck will develop personalized cancer vaccines that utilize
Moderna’s mRNA vaccine technology to encode a patient’s specific
neoantigens, unique mutations present in that specific patient’s tumor.
When injected into a patient, the vaccine will be designed to elicit a
specific immune response that will recognize and destroy cancer cells.
The companies believe that the mRNA-based personalized cancer vaccines’
ability to specifically activate an individual patient’s immune system
has the potential to be synergistic with checkpoint inhibitor therapies,
including Merck’s anti-PD-1 therapy, KEYTRUDA®
(pembrolizumab). In addition, Moderna has developed a rapid cycle time,
small-batch manufacturing technique that will uniquely allow the company
to supply vaccines tailored to individual patients within weeks.
Under the terms of the agreement, Merck will make an upfront cash
payment to Moderna of $200 million, which Moderna will use to lead all
research and development efforts through proof of concept. The
development program will entail multiple studies in several types of
cancer and include the evaluation of mRNA-based personalized cancer
vaccines in combination with Merck’s KEYTRUDA® (pembrolizumab). Moderna
will also utilize the upfront payment to fund a portion of the build-out
of a GMP manufacturing facility in suburban Boston for the purpose of
personalized cancer vaccine manufacturing.
Following human proof of concept studies, Merck has the right to elect
to make an additional undisclosed payment to Moderna. If exercised, the
two companies will then equally share cost and profits under a worldwide
collaboration for the development of personalized cancer vaccines.
Moderna will have the right to elect to co-promote the personalized
cancer vaccines in the U.S. The agreement entails exclusivity around
combinations with KEYTRUDA. Moderna and Merck will each have the ability
to combine mRNA-based personalized cancer vaccines with other (non-PD-1)
“Combining immunotherapy with vaccine technology may be a new path
toward improving outcomes for patients,” said Dr. Roger Perlmutter,
president, Merck Research Laboratories. “While the area of personalized
cancer vaccine research has faced challenges in the past, there have
been many recent advances, and we believe that working with Moderna to
combine an immuno-oncology approach, using KEYTRUDA, with
mRNA-based personalized cancer vaccines may have the potential to
transform the treatment of cancer.”
“Our team has made significant progress since beginning our work in
personalized cancer vaccines just last year. Through this collaboration
with Merck, we are now well-positioned to accelerate research and
development with a goal of entering the clinic in 2017, as well as to
apply our unique GMP manufacturing capabilities to support the rapid
production of these highly individualized vaccines,” said
Stéphane Bancel, chief executive officer of Moderna. “We value our
continued collaboration with Merck, and we look forward to working
together to harness the potential of personalized cancer vaccines and
immuno-oncology to bring a new treatment paradigm to patients.”
Merck and Moderna have an existing collaboration and license agreement
focused on the discovery and development of mRNA-based infectious
disease vaccines and passive immunity treatments. Moderna is also
advancing its own pipeline of infectious disease vaccine candidates and
currently has two phase 1 studies underway in Europe and the U.S.
KEYTRUDA is a humanized monoclonal antibody that works by increasing the
ability of the body’s immune system to help detect and fight tumor
cells. KEYTRUDA blocks the interaction between PD-1 and its ligands,
PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both
tumor cells and healthy cells.
KEYTRUDA is indicated for the treatment of patients with unresectable or
KEYTRUDA is also indicated for the treatment of patients with metastatic
non-small cell lung cancer (NSCLC) whose tumors express PD-L1 as
determined by an FDA-approved test with disease progression on or after
platinum-containing chemotherapy. Patients with EGFR or ALK genomic
tumor aberrations should have disease progression on FDA-approved
therapy for these aberrations prior to receiving KEYTRUDA. 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.
KEYTRUDA is administered at a dose of 2 mg/kg as an intravenous infusion
over 30 minutes every three weeks for the approved indications.
Selected Important Safety Information for KEYTRUDA
Immune-mediated pneumonitis, including fatal cases, occurred in patients
receiving KEYTRUDA® (pembrolizumab). Pneumonitis occurred in 32 (2.0%)
of 1567 patients with melanoma, including Grade 1 (0.8%), 2 (0.8%), and
3 (0.4%) pneumonitis. Pneumonitis occurred in 19 (3.5%) of 550 patients
with NSCLC, including Grade 2 (1.1%), 3 (1.3%), 4 (0.4%), or 5 (0.2%)
pneumonitis and more frequently in patients with a history of
asthma/chronic obstructive pulmonary disease (5.4%) or prior thoracic
radiation (6.0%). 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
or recurrent Grade 2 pneumonitis.
Immune-mediated colitis occurred in 31 (2%) of 1567 patients with
melanoma, including Grade 2 (0.5%), 3 (1.1%), and 4 (0.1%) colitis.
Immune-mediated colitis occurred in 4 (0.7%) of 550 patients with NSCLC,
including Grade 2 (0.2%) or 3 (0.4%) colitis. Monitor patients for signs
and symptoms of colitis. Administer corticosteroids for Grade 2 or
greater colitis. Withhold KEYTRUDA (pembrolizumab) for Grade 2 or 3;
permanently discontinue KEYTRUDA for Grade 4 colitis.
Immune-mediated hepatitis occurred in patients receiving KEYTRUDA.
Hepatitis occurred in 16 (1%) of 1567 patients with melanoma, including
Grade 2 (0.1%), 3 (0.7%), and 4 (0.1%) hepatitis. 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 13 (0.8%) of 1567 patients with melanoma,
including Grade 2 (0.3%), 3 (0.3%), and 4 (0.1%) hypophysitis.
Hypophysitis occurred in 1 (0.2 %) of 550 patients with NSCLC, which was
Grade 3 in severity. Monitor patients for signs and symptoms of
hypophysitis (including hypopituitarism and adrenal insufficiency).
Administer corticosteroids and hormone replacement as clinically
indicated. Withhold KEYTRUDA for Grade 2; withhold or discontinue for
Grade 3 or 4 hypophysitis.
Hyperthyroidism occurred in 51 (3.3%) of 1567 patients with melanoma,
including Grade 2 (0.6%) and 3 (0.1%) hyperthyroidism. Hypothyroidism
occurred in 127 (8.1%) of 1567 patients with melanoma, including Grade 3
(0.1%) hypothyroidism. Hyperthyroidism occurred in 10 (1.8%) of 550
patients with NSCLC, including Grade 2 (0.7%) or 3 (0.3%)
hyperthyroidism. Hypothyroidism occurred in 38 (6.9%) of 550 patients
with NSCLC, including Grade 2 (5.5%) or 3 (0.2%) hypothyroidism. 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 replacement
hormones for hypothyroidism and manage hyperthyroidism with thionamides
and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for
Grade 3 or 4 hyperthyroidism.
Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 3
(0.1%) of 2117 patients. Monitor patients for hyperglycemia or other
signs and symptoms of diabetes. Administer insulin for type 1 diabetes,
and withhold KEYTRUDA and administer anti-hyperglycemics in patients
with severe hyperglycemia.
Immune-mediated nephritis occurred in patients receiving KEYTRUDA.
Nephritis occurred in 7 (0.4%) of 1567 patients with melanoma including,
Grade 2 (0.2%), 3 (0.2%), and 4 (0.1%) nephritis. Monitor patients for
changes in renal function. Administer corticosteroids for Grade 2 or
greater nephritis. Withhold KEYTRUDA (pembrolizumab) for Grade 2;
permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis.
Other clinically important immune-mediated adverse reactions can occur.
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 ® (pembrolizumab)
and administer corticosteroids. Upon improvement to Grade 1 or less,
initiate corticosteroid taper and continue to taper over at least 1
month. Based on limited data from clinical studies in patients whose
immune-related adverse reactions could not be controlled with
corticosteroid use, administration of other systemic immunosuppressants
can be considered. Resume KEYTRUDA when the adverse reaction remains at
Grade 1 or less following corticosteroid taper. Permanently discontinue
KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs
and for any life-threatening immune-mediated adverse reaction.
The following clinically significant, immune-mediated adverse reactions
occurred in less than 1% (unless otherwise indicated) of 1567 patients
with melanoma: arthritis (1.6%), exfoliative dermatitis, bullous
pemphigoid, uveitis, myositis, Guillain-Barré syndrome, myasthenia
gravis, vasculitis, pancreatitis, hemolytic anemia, and partial seizures
arising in a patient with inflammatory foci in brain parenchyma. The
following clinically significant, immune-mediated adverse reactions
occurred in less than 1% of 550 patients with NSCLC: rash, vasculitis,
hemolytic anemia, serum sickness, and myasthenia gravis.
Severe and life-threatening infusion-related reactions have been
reported in 3 (0.1%) of 2117 patients. Monitor patients for signs and
symptoms of infusion related reactions including rigors, chills,
wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever.
For Grade 3 or 4 reactions, stop infusion and permanently discontinue
Based on its mechanism of action, KEYTRUDA can 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.
In Trial 6, KEYTRUDA was discontinued due to adverse reactions in 9% of
555 patients with advanced melanoma; adverse reactions leading to
discontinuation in more than one patient were colitis (1.4%), autoimmune
hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and
cardiac failure (0.4%). Adverse reactions leading to interruption of
KEYTRUDA occurred in 21% of patients; the most common (≥1%) was diarrhea
(2.5%). The most common adverse reactions with KEYTRUDA vs ipilimumab
were fatigue (28% vs 28%), diarrhea (26% with KEYTRUDA), rash (24% vs
23%), and nausea (21% with KEYTRUDA). Corresponding incidence rates are
listed for ipilimumab only for those adverse reactions that occurred at
the same or lower rate than with KEYTRUDA (pembrolizumab).
In Trial 2, KEYTRUDA was discontinued due to adverse reactions in 12% of
357 patients with advanced melanoma; the most common (≥1%) were general
physical health deterioration (1%), asthenia (1%), dyspnea (1%),
pneumonitis (1%), and generalized edema (1%). Adverse reactions leading
to interruption of KEYTRUDA occurred in 14% of patients; the most common
(≥1%) were dyspnea (1%), diarrhea (1%), and maculo-papular rash (1%).
The most common adverse reactions with KEYTRUDA vs chemotherapy were
fatigue (43% with KEYTRUDA), pruritus (28% vs 8%), rash (24% vs 8%),
constipation (22% vs 20%), nausea (22% with KEYTRUDA), diarrhea (20% vs
20%), and decreased appetite (20% with KEYTRUDA). Corresponding
incidence rates are listed for chemotherapy only for those adverse
reactions that occurred at the same or lower rate than with KEYTRUDA.
KEYTRUDA was discontinued due to adverse reactions in 14% of 550
patients with NSCLC. Serious adverse reactions occurred in 38% of
patients. The most frequent serious adverse reactions reported at least
2% of patients were pleural effusion, pneumonia, dyspnea, pulmonary
embolism, and pneumonitis. The most common adverse reactions (reported
in at least 20% of patients) were fatigue (44%), cough (29%), decreased
appetite (25%), and dyspnea (23%).
No formal pharmacokinetic drug interaction studies have been conducted
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 and for 4 months after the final dose.
Safety and effectiveness of KEYTRUDA have not been established in
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
As part of our focus on cancer, Merck is committed to exploring the
potential of immuno-oncology with one of the fastest-growing development
programs in the industry. We are currently executing an expansive
research program that includes more than 300 clinical trials evaluating
our anti-PD-1 therapy across more than 30 tumor types. We also continue
to strengthen our immuno-oncology portfolio through strategic
acquisitions and are prioritizing the development of several promising
immunotherapeutic candidates with the potential to improve the treatment
of advanced cancers.
For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.
For 125 years, Merck has been 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,
About Moderna Therapeutics
Moderna is a clinical stage pioneer of messenger
RNA Therapeutics™, an entirely new in vivo drug technology that
produces human proteins, antibodies and entirely novel protein
constructs inside patient cells, which are in turn secreted or active
intracellularly. This breakthrough platform addresses currently
undruggable targets and offers a potentially superior alternative to
existing drug modalities for a wide range of diseases and conditions.
Moderna is developing and plans to commercialize its innovative mRNA
drugs through its own ventures and its strategic relationships with
established pharmaceutical and biotech companies. Its current ventures
focused on oncology, Valera,
focused on infectious diseases, Elpidera,
focused on rare diseases, and Caperna,
focused on personalized cancer vaccines. Cambridge-based Moderna is
privately held and currently has strategic agreements with AstraZeneca,
Pharmaceuticals and Merck.
To learn more, visit www.modernatx.com.
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“company”) includes “forward-looking statements” within the meaning of
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respect to pipeline products that the products will receive the
necessary regulatory approvals or that they will prove to be
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Please see Prescribing Information for KEYTRUDA (pembrolizumab) at
Patient Information/Medication Guide for KEYTRUDA at
Pamela Eisele, 267-305-3558
Courtney Ronaldo, 908-236-1108
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