-- Early data from investigator-initiated pilot
study of CDX-301/radiation therapy combination in patients with
advanced NSCLC show promising effect on tumor burden even in
non-irradiated tumors --
Celldex Therapeutics, Inc. (NASDAQ:CLDX) today announced promising
early data from an investigator-initiated pilot study evaluating
the combination of CDX-301 and stereotactic body radiotherapy
(SBRT) in patients with advanced non-small cell lung cancer
(NSCLC). CDX‑301 (recombinant human Flt3 ligand) is a potent
hematopoietic cytokine that uniquely expands dendritic cells and
hematopoietic stem cells. This translational study is the
culmination of significant preclinical research into strategically
combining radiation and immunotherapy to effectively treat
aggressive tumors and is supported by a Small Business Innovation
Research (SBIR) grant from the National Cancer Institute to Celldex
in collaboration with Albert Einstein College of Medicine, part of
Montefiore. The data were presented during a plenary session at the
American Association for Cancer Research (AACR) Annual Meeting 2018
earlier this week by Nitin Ohri, M.D., Attending Physician,
Montefiore and Assistant Professor, Department of Radiation
Oncology, Einstein, and principal investigator on the study.
The concept that increasing the number of dendritic cells with
Flt3 ligand combined with an ablative course of radiation to the
primary tumor induces a systemic anti-tumor response, suppresses
metastases and promotes survival and immune memory was demonstrated
through preclinical studies led by Dr. Chandan Guha and colleagues
at the Einstein College of Medicine.1 Based on this seminal work, a
Phase 2 pilot study of CDX-301 in combination with SBRT was
initiated at the Montefiore Einstein Center for Cancer Care. The
study is currently enrolling up to 29 patients, and the primary
objective is progression-free survival at four months after
treatment (PFS4). Key secondary objectives include evaluation of
dose-limiting toxicities and response rate in non-irradiated
tumors, where tumor shrinkage from radiation therapy or CDX-301
independently would not be expected. Responses were particularly
impressive when classified by PERCIST (PET Response in Solid
Tumors) criteria, in which a partial response is at least a 45%
reduction of total glycolytic activity, a volumetric measure of
disease burden. The presentation included data from nine patients,
seven of whom were previously treated with anti-PD(L)1 checkpoint
inhibitors. The one-week course of treatment included subcutaneous
injections of CDX-301 and SBRT directed to a single lung tumor
lesion.
Key Highlights
- PFS4 was achieved in 56% (5/9) of patients overall (n=9;
enrollment ongoing) and in 100% (5/5) of patients who experienced
partial responses (PRs) by PERCIST
- Notably, PRs were observed in non-irradiated tumors in 56%
(5/9) of patients at two months; 3 PRs (3/9) were confirmed by
immune-related response criteria (irRC)
- In the patients previously treated with immune checkpoint
inhibitors, 71% (5/7) experienced PRs and PFS4 versus 0% (0/2) in
patients not treated with an anti-PD(L)1 therapy
- SBRT in combination with CDX-301 induced and reactivated
anti-tumor immune responses in patients who had progressive disease
on checkpoint inhibitors
- No dose-limiting toxicities were observed
“The combination of CDX-301 and radiation produced a significant
decrease in tumor burden after just one course of treatment, even
in non-irradiated tumors. We saw a longer period of survival for
several of our patients with advanced lung cancer,” said Dr. Ohri.
“We are looking forward to completing enrollment in the study,
determining an optimal dosing regimen and identifying additional
immune modulating agents.”
“Of particular interest is the potential correlation of clinical
benefit with those patients who previously were treated with PD-1
blockade therapy, suggesting SBRT and CDX-301 may be able to reboot
the immune system for an effective anti-tumor response,” said Tibor
Keler, Ph.D., Executive Vice President and Chief Scientific Officer
of Celldex Therapeutics. “We believe that the activity of this
combination may potentially be augmented by the addition of
CDX-1140, our unique CD40 agonist antibody, which is designed to
activate dendritic cells and is currently in a Phase 1
dose-escalation study.”
Additionally, Celldex and its collaborating investigators
presented four posters at the AACR Annual Meeting 2018:
- Poster CT058: Molecular and clinical activity of
CDX-3379, an anti-ErbB3 monoclonal antibody, in head and neck
squamous cell carcinoma: A preoperative "window of opportunity"
study (Duvvuri, et al)A “window-of-opportunity” study
enrolled 12 patients to evaluate the effect of CDX-3379 on
phosphorylated ErbB3 (pErbB3) and other potential biomarkers in
patients with head and neck squamous cell carcinoma (HNSCC).
Patients with newly diagnosed HNSCC received two doses of CDX-3379,
at a two-week interval prior to tumor resection. CDX-3379 reduced
pErbB3 levels in 83% (10/12) of patient samples, with greater than
or equal to 50% decreases in 58% of patients (7/12), which met the
primary study objective. Stable disease was observed in 92% (11/12)
of patients prior to surgery, and a patient with HPV-negative
disease experienced significant tumor shrinkage (92% in primary
tumor; 26% in metastatic lesion). CDX-3379 was well-tolerated, and
no treatment-related adverse events were observed.
- Poster 876: Effective reduction of PD-L1 expression by
simultaneous blockade of EGFR and HER3 (ErbB3) in head and neck
cancer (Chen, et al)Investigators examined the effects of
combining CDX-3379, a monoclonal antibody targeting ErbB3, and
cetuximab, a monoclonal antibody targeting EGFR, in xenograft
models of head and neck squamous cell carcinoma. Combining CDX-3379
and cetuximab inhibited tumor growth more potently than cetuximab
alone. Mechanistic studies demonstrated a reduction of PD-L1
expression from the combination.
- Poster 3816: Efficacy of CDX-1140, an agonist CD40
antibody, in preclinical tumor models (Thomas, et
al)Building off previously presented preclinical work,
CDX-1140 was further characterized showing tumor shrinkage and
prolonged survival in several xenograft models. These preclinical
studies support the potential of CDX-1140 having direct anti-tumor
effects on CD40-positive tumors that may supplement its activity as
an immune activating agent.
- Poster 5624: Development of novel bispecific immune
modulating antibodies (Vitale, et al)Celldex’s initial
bispecific antibody (BsAb) couples CD27 co-stimulation with
blockade of the PD-L1/PD-1 pathway, using novel highly active
anti-PD-L1 antibodies. The BsAb was more potent in human T cell
activation and anti-tumor activity, compared to the combined CD27
and PD-L1 antibodies. Enhanced efficacy has been attributed to more
efficient cross-linking of the BsAb/CD27 receptor, resulting in
stronger T cell activation.
The CDX-301 presentation and all posters are available on the
"Publications" page of the "Science" section of the Celldex
website.
About
CDX‑301CDX-301 (Flt3L)
is a potent hematopoietic cytokine that has demonstrated a unique
capacity to increase the number of circulating dendritic cells in
both laboratory and clinical studies, including CD141+ dendritic
cells critical for cross-presenting tumor antigens to cytotoxic T
cells. In addition, CDX‑301 has shown impressive results in models
of cancer, infectious diseases and inflammatory/autoimmune
diseases. Celldex believes this ligand may hold significant
opportunity for synergistic development in combination with other
proprietary molecules in the Company's portfolio.
About CDX-3379CDX-3379 is a human
immunoglobulin G1 lambda (IgG1λ) monoclonal antibody that
selectively binds and inhibits ErbB3 activity. ErbB3 may be an
important receptor regulating cancer cell growth and survival as
well as resistance to targeted therapies, and it is expressed in
many cancers, including head and neck, thyroid, breast, lung and
gastric cancers, as well as melanoma. The proposed mechanism of
action for CDX-3379 sets it apart from other drugs in development
in this class due to its ability to block both ligand-independent
and ligand-dependent ErbB3 signaling by binding to a unique
epitope. It has a favorable pharmacologic profile, including a
longer half-life and slower clearance relative to other drug
candidates in this class. CDX-3379 also has potential to enhance
anti-tumor activity and/or overcome resistance in combination with
other targeted and cytotoxic therapies to directly kill tumor
cells.
About CDX-1140CDX-1140 is a fully human
monoclonal antibody targeted to CD40, a key activator of immune
response that is found on dendritic cells, macrophages and B cells
and is also expressed on many cancer cells. Potent CD40 agonist
antibodies have shown encouraging results in early clinical
studies; however, systemic toxicity associated with broad CD40
activation has limited their dosing. CDX-1140 has unique properties
relative to other CD40 agonist antibodies: potent agonist activity
is independent of Fc receptor interaction, contributing to more
consistent, controlled immune activation; CD40L binding is not
blocked, leading to potential synergistic effects of agonist
activity with activated T cells in lymph nodes and tumors; and the
antibody does not promote cytokine production in whole blood
assays. CDX-1140 activates dendritic cells and other CD40
expressing cells and has also shown direct anti-tumor activity in
preclinical models of lymphoma. The Company believes that the
potential for CDX-1140 will be best defined in combination studies
with other immunotherapies or conventional cancer treatments.
References1. Chakravarty, et al. Cancer Res.
1999. 59(24):6028-32.
About Celldex Therapeutics, Inc.Celldex is
developing targeted therapeutics to address devastating diseases
for which available treatments are inadequate. Our pipeline
includes antibodies, antibody-drug conjugates and other
protein-based therapeutics derived from a broad set of
complementary technologies which have the ability to engage the
human immune system and/or directly inhibit tumors to treat
specific types of cancer or other diseases. Visit
www.celldex.com.
Forward Looking StatementThis release contains
"forward-looking statements" made pursuant to the safe harbor
provisions of the Private Securities Litigation Reform Act of 1995.
These statements are typically preceded by words such as
"believes," "expects," "anticipates," "intends," "will," "may,"
"should," or similar expressions. These 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 or that those goals will be
achieved, 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 Company 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; our ability to realize the
anticipated benefits from the acquisition of Kolltan and to operate
the combined business efficiently; the uncertainties inherent in
clinical testing and accruing patients for clinical trials; our
limited experience in bringing programs through Phase 3 clinical
trials; our ability to manage and successfully complete multiple
clinical trials and the research and development efforts for our
multiple products at varying stages of development; the
availability, cost, delivery and quality of clinical and commercial
grade materials produced by our own manufacturing facility or
supplied by contract manufacturers, who may be our sole source of
supply; 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 and quarterly reports on Form
10-Q.
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.
Contacts
Sarah CavanaughSenior Vice President, Corporate Affairs &
AdministrationCelldex Therapeutics, Inc.(781)
433-3161scavanaugh@celldex.com
Charles LilesAssociate Director, Investor Relations & Corp
CommunicationsCelldex Therapeutics, Inc.(617)
383-3433cliles@celldex.com
Celldex Therapeutics (NASDAQ:CLDX)
Historical Stock Chart
From Mar 2024 to Apr 2024
Celldex Therapeutics (NASDAQ:CLDX)
Historical Stock Chart
From Apr 2023 to Apr 2024