--First clinical study to demonstrate that an
off-the-shelf vaccine targeting dendritic cells can safely lead to
robust humoral and cellular immunity--
Celldex Therapeutics, Inc. (Nasdaq:CLDX) announced today that final
data from its Phase 1 study of CDX-1401 in solid tumors, including
long-term patient follow-up, have been published in Science
Translational Medicine (Vol 6 Issue 232). The data demonstrate
robust antibody and T cell responses and evidence of clinical
benefit in patients with very advanced cancers and suggest that
CDX-1401 may predispose patients to better outcomes on subsequent
therapy with checkpoint inhibitors. CDX-1401 is an off-the-shelf
vaccine consisting of a fully human monoclonal antibody with
specificity for the dendritic cell receptor DEC-205 linked to the
NY-ESO-1 tumor antigen. The vaccine is designed to activate the
patient's immune system against cancers that express the tumor
marker NY-ESO-1. While the function of NY-ESO-1 continues to be
explored, references in the literature suggest that its expression
might reflect the acquisition of properties that cancers find
useful, such as immortality, self-renewal, migratory ability and
the capacity to invade.
The Phase 1 study of CDX-1401 is the first clinical study to
demonstrate that an off-the-shelf vaccine that targets dendritic
cells in vivo through DEC-205 can safely lead to robust humoral and
cellular immunity—overcoming a significant challenge in the
development of protein based vaccines. Targeting protein antigens
to the DEC-205 receptor on dendritic cells was pioneered by the
late Ralph Steinman, MD, a member of Celldex's Scientific Advisory
Board. Dr. Steinman received the 2011 Nobel Prize in Physiology or
Medicine for his discovery of the dendritic cell and its role in
adaptive immunity. This now-proven ability to target proteins, like
NY-ESO-1, to dendritic cells to generate potent immune responses
specific to these proteins represents a promising approach for the
next generation of vaccines against pathogens and cancer.
"CDX-1401 offers a novel, well-tolerated and practical approach
to generating protein specific immunity that can be readily
combined with other treatment strategies to boost immunity against
pathogens and tumors," said Dr. Madhav Dhodapkar, MBBS, Arthur H.
and Isabel Bunker Professor of Medicine and Immunobiology, Chief of
the Section of Hematology at the Department of Internal Medicine
and Clinical Research Program Leader of the Hematology Program at
Yale Cancer Center and lead author of the paper. "The preliminary
findings in patients who received therapy with a checkpoint
inhibitor following the vaccine provide further rationale for
combination immunotherapy strategies, meriting further
investigation."
Thomas Davis, MD, Senior Vice President and Chief Medical
Officer of Celldex Therapeutics added, "CDX-1401 has overcome a
significant historical challenge in the development of protein
based vaccines by successfully targeting dendritic cells in vivo.
It now sits at the forefront of a new generation of off-the-shelf
dendritic cell targeted vaccines that we believe hold significant
promise. Based on the results observed in this Phase 1 study, we
expect CDX-1401 to enter at least two combination studies this year
with both our own investigational therapies and external therapies
in melanoma and other indications where we believe a dendritic cell
vaccine regimen could play an important role."
Initial results from the Phase 1 study of CDX-1401 were
presented at the 2012 Society for Immunotherapy of Cancer (SITC)
Annual Meeting. The manuscript published today expands upon this
data and includes longer-term patient follow up.
CDX-1401 Phase 1 Study Overview and Results
The study was designed to assess the safety, immunogenicity and
clinical activity of escalating doses of CDX-1401 with TLR agonists
(resiquimod and/or Poly ICLC (Hiltonol®) in 45 patients with
advanced malignancies refractory to all available therapies.
CDX-1401 was well tolerated, with no dose limiting or grade 3
toxicities reported. The most frequently reported adverse events
were administration site reaction, fatigue, nausea and chills.
Treatment induced humoral and cellular immunity to NY-ESO-1 in
patients with NY-ESO-1 expressing tumors across various dose levels
and adjuvant combinations.
Significant anti-NY-ESO-1 titers occurred in 79% (33/42) of
evaluable patients, with high titers (>1:10,000) in 52% and very
high titers (>1:100,000) in 33% of patients. Similarly strong
humoral immunity developed in each cohort and in patients with or
without confirmed NY-ESO-1 expression in their tumor. Approximately
54% of patients with NY-ESO-1 positive tumors had anti-NY-ESO-1
titers at baseline and most increased after vaccination.
NY-ESO-1-specific T cell responses were absent or low at baseline,
but increased post-vaccination in 56% of evaluable patients,
including both CD4 and/or CD8 T cell responses. Durability of the T
cell response was demonstrated in two patients from whom samples
from additional cycles of CDX-1401 treatment were available. In
these patients, the induction of NY-ESO-1 specific T cells was
maintained through three cycles (approximately seven months) of
treatment.
Thirteen patients experienced stable disease, with a median
duration of 6.7 months (2.4+ to 13.4). In addition, two patients
with melanoma experienced tumor regression of about 20% shrinkage
in target lesions. The detection of NY-ESO-1 expression in tumor
tissue did not appear to correlate with patient outcome. Stable
disease was seen in 7/27 (26%) of the patients with NY-ESO-1
expression, and in 5/15 (33%) of those lacking NY-ESO-1 expression.
However, the proportion of patients with stable disease was higher
for those who maintained or developed NY-ESO-1 specific T cell
responses. Stable disease was seen in 3/6 (50%) patients who
entered the study with pre-existing cellular immunity to NY-ESO-1,
and all three had increased responses while on study. For the
remaining 13 patients who developed cellular immunity while on
treatment, 6 (46%) experienced stable disease. In contrast, stable
disease was seen in only 2/15 (13%) patients who did not develop
cellular immunity to NY-ESO-1. Interestingly, 4/6 (67%) patients
that displayed the strongest responses (>50 IFN-gamma spots per
2 x 105 PBMC) also experienced stable disease. The association of
cellular response and stable disease does not appear to be a
consequence of extended duration of therapy. Peak responses were
observed in the first treatment cycle for seven of the nine
patients with stable disease who developed cellular immunity.
Of the 45 patients in the Phase 1 study, eight went on to
receive subsequent therapy of either Yervoy® or an investigational
checkpoint inhibitor and six of these patients had objective tumor
regression. Six patients with melanoma received Yervoy within three
months of treatment with CDX-1401 and four (67%) had objective
tumor responses, including one complete response, which compares
favorably to the overall response rate of 11% previously reported
in metastatic melanoma patients treated with single-agent Yervoy.
In addition, two patients with non-small cell lung cancer received
an investigational checkpoint blockade within two months of
completing treatment with CDX-1401 and both achieved partial
responses. All six of the responding patients had tumors confirmed
to express NY-ESO-1. Interestingly, five also developed
NY-ESO-1-specific cellular response, while four also developed or
maintained NY-ESO-1 specific humoral response, by the end of
treatment with CDX-1401.
Hiltonol® is a registered trademark of Oncovir, and Yervoy® is a
registered trademark of Bristol Myers Squibb. About
CDX-1401 CDX-1401 is a next-generation, off-the-shelf
cancer vaccine designed to activate the patient's immune system
against cancers that express the tumor marker, NY-ESO-1. CDX-1401
consists of a fully human monoclonal antibody with specificity for
the dendritic cell receptor DEC-205 genetically linked to the
NY-ESO-1 tumor antigen. Celldex has accessed NY-ESO-1 through a
licensing agreement with the Ludwig Institute for Cancer Research.
By selectively delivering the NY-ESO-1 antigen to dendritic cells
in the body, CDX-1401 is intended to induce robust immune responses
against the antigen-expressing cancer cells.
About Celldex Therapeutics, Inc.
Celldex is developing targeted therapeutics to address
devastating diseases for which available treatments are inadequate.
Our pipeline is built from a proprietary portfolio of antibodies
and immunomodulators used alone and in strategic combinations to
create novel, disease-specific therapies that induce, enhance or
suppress the body's immune response. Visit www.celldex.com.
Safe Harbor Statement Under the Private Securities
Litigation Reform Act of 1995:
This release contains "forward-looking statements" made pursuant
to the safe harbor provisions of the Private Securities Litigation
Reform Act of 1995, including those related to the Company's
strategic focus and the future development and commercialization
(by Celldex and others) of rindopepimut (CDX-110), glembatumumab
vedotin ("glemba"; CDX-011), Varlilumab (CDX-1127), CDX-1401,
CDX-301, CDX-014 and other products. Forward-looking statements
reflect management's current knowledge, assumptions, judgment and
expectations regarding future performance or events. Although
management believes that the expectations reflected in such
statements are reasonable, they give no assurance that such
expectations will prove to be correct and you should be aware that
actual results could differ materially from those contained in the
forward-looking statements. Forward-looking statements are subject
to a number of risks and uncertainties, including, but not limited
to, our ability to successfully complete research and further
development and commercialization of rindopepimut, glembatumumab
vedotin and other drug candidates, our ability to obtain additional
capital to meet our long-term liquidity needs on acceptable terms,
or at all, including the additional capital which will be necessary
to complete the clinical trials that we have initiated or plan to
initiate; the uncertainties inherent in clinical testing; our
limited experience in bringing programs through Phase 3 clinical
trials; our ability to manage research and development efforts for
multiple products at varying stages of development; the timing,
cost and uncertainty of obtaining regulatory approvals; the failure
of the market for the Company's programs to continue to develop;
our ability to protect the Company's intellectual property; the
loss of any executive officers or key personnel or consultants;
competition; changes in the regulatory landscape or the imposition
of regulations that affect the Company's products; and other
factors listed under "Risk Factors" in our annual report on Form
10-K.
All forward-looking statements are expressly qualified in their
entirety by this cautionary notice. You are cautioned not to place
undue reliance on any forward-looking statements, which speak only
as of the date of this release. We have no obligation, and
expressly disclaim any obligation, to update, revise or correct any
of the forward-looking statements, whether as a result of new
information, future events or otherwise.
CONTACT: Company Contact:
Sarah Cavanaugh
Vice President of Investor Relations &
Corp Communications
Celldex Therapeutics, Inc.
(781) 433-3161
scavanaugh@celldex.com
Media Inquiries:
Dan Budwick
Pure Communications, Inc.
(973) 271-6085
dan@purecommunicationsinc.com
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