Celldex Therapeutics, Inc. (NASDAQ:CLDX) today announced data from
multiple presentations at the Society for Immunotherapy of Cancer’s
(SITC) 35th Anniversary Annual Meeting & Pre-Conference
Programs (SITC 2020). An interim update from the Company’s ongoing
Phase 1 study of its CD40 agonist antibody, CDX-1140, and
preclinical data from its AXL discovery program were presented at
the meeting. In addition, the Phase 1 study design for the
Company’s bispecific candidate, CDX-527, which couples CD27
co-stimulation with blockade of the PD-L1/PD-1 pathway, were also
presented in a clinical trial in progress poster.
“CDX-1140 continues to emerge as a potential best in class CD40
agonist,” said Diane C. Young, MD, Senior Vice President and Chief
Medical Officer of Celldex Therapeutics. “At SITC, we reported data
from the monotherapy and CDX-301 combination cohorts at the
recommended 1.5 mg/kg CDX-1140 dose, which provided high systemic
exposure that led to effective modulation of the tumor
microenvironment to a more pro-inflammatory and less suppressive
state. We believe this supports the clinical activity we continue
to see in very difficult to treat, refractory tumor types,
including tumor shrinkage and necrosis in a number of patients with
squamous cell head and neck cancers and a durable complete
response, or CR, in a patient with heavily pre-treated follicular
lymphoma.
We are building on this strong foundation by exploring CDX-1140
in combination with other key mechanisms that could be
complementary, including with the PD-1 inhibitor pembrolizumab. At
SITC, we reported preliminary safety data from this cohort,
demonstrating that the combination is well tolerated, and announced
the initiation of expansion cohorts with pembrolizumab in both head
and neck squamous cell carcinoma and non-small cell lung cancer. We
also recently initiated an expansion cohort with chemotherapy in
pancreatic cancer which is supported by strong preclinical studies
and promising early clinical data with CD40 agonist antibodies.
In addition to the CDX-1140 data, we were pleased to present the
trial design from our ongoing study of the first bispecific
candidate from our platform, CDX-527, and emerging data from our
preclinical program targeting Axl, which is also being developed as
a potential bispecific antibody. We look forward to updating across
these programs next year,” concluded Dr. Young.
Presentation Highlights
CDX-1140 Presentation Highlights
(Poster #405): CD40,
expressed on dendritic cells and other antigen presenting cells, is
an important target for immunotherapy, as it plays a critical role
in the activation of innate and adaptive immune responses. CDX-1140
is a fully human agonist anti-CD40 monoclonal antibody that was
specifically designed to balance good systemic exposure and safety
with potent biological activity, a profile which differentiates
CDX-1140 from other CD40-activating antibodies.
CDX-1140 is currently in a Phase 1 dose escalation and expansion
study. The study includes monotherapy and combination cohorts,
including with CDX-301, Celldex’s dendritic cell growth factor,
with the PD-1 inhibitor pembrolizumab in patients who have
progressed on checkpoint therapy and in combination with standard
of care chemotherapy (gemcitabine and nab-paclitaxel) in first line
metastatic pancreatic cancer.
Prior data presented at SITC 2019 established the maximum
tolerated dose (MTD) and recommended dose for continued study at
1.5 mg/kg—one of the highest systemic dose levels in the CD40
agonist class. The update presented at SITC 2020 focused on
patients treated at the MTD from both the monotherapy (n=25) and
CDX-301 (n=16) combination cohorts. In addition, preliminary safety
data from the combination cohort with pembrolizumab (n=9; 4 at 0.72
mg/kg and 5 at 1.5 mg/kg CDX-1140) were also presented.
- CDX-1140 monotherapy and in combination with CDX-301 or
pembrolizumab was generally well tolerated with mostly grade 1 or
grade 2 drug related adverse events.
- Clinical activity both as a monotherapy and in combination with
CDX-301 has been previously reported for CDX-1140 at varying doses,
including an unconfirmed partial response (uPR) and tumor
cavitation. At SITC 2020, analysis was focused on patients treated
at the MTD and recommended dose of 1.5 mg/kg. 41 patients had been
treated at the 1.5 mg/kg dose at the time of data cutoff; 29
patients had post-treatment scans performed and five patients had
not reached their first post-treatment response assessment.
- Activity at 1.5mg/kg dose of CDX-1140 to date included:
- An ongoing (6+ months) complete response (CR) in a patient with
follicular lymphoma treated with CDX-1140 in combination with
CDX-301;
- Notable tumor shrinkage and/or necrosis in 6 patients with
squamous cell head and neck cancer (SCCHN), including extensive
tumor cavitation/necrosis of a large baseline protruding neck mass
associated with decreased tumor pain in a patient; and,
- Stable disease (n=10) for 11 to 32 weeks.
- CDX-1140 at the recommended dose of 1.5 mg/kg provided good
systemic exposure that enhanced the distribution into tissues and
tumor and resulted in marked changes in the tumor microenvironment
(TME) consistent with a more inflammatory and less
immunosuppressive state as demonstrated by gene expression
analysis.
- Interferon signaling and cytotoxicity pathways were most highly
upregulated, while immunosuppression via TGFb signaling and
metastatic pathways were downregulated, marking the first clear
demonstration in patients of biological activity within the TME for
a systemically administered agonist anti-CD40 mAb.
- Pre-treatment of patients with CDX-301 greatly increased the
number of circulating dendritic cells prior to CDX-1140
administration and peripheral blood mononuclear cells (PBMCs)
isolated from CDX-301 pretreated patients were more responsive to
CDX-1140 than PBMCs from non-pretreated patients.
Ongoing cohorts:
- The combination of CDX-1140 with pembrolizumab has completed
the safety run-in and expansion cohorts in patients with
checkpoint-refractory squamous cell head and neck cancer and
non-small cell lung cancer have initiated.
- The combination of CDX-1140 with gemcitabine/nab-paclitaxel
recently opened to enrollment to patients with previously untreated
metastatic pancreatic adenocarcinoma.
- Data updates from these cohorts are expected in the first half
of 2021.
Axl Preclinical Program (Poster:
#550): Axl is a member of the TAM
(Tyro3/Axl/MerTK) family of receptor tyrosine kinases and a
negative regulator of innate immunity. Activation of Axl through
its ligand, Gas6, leads to suppression of myeloid cell activity,
while its activation in tumor cells drives tumor growth and
metastasis, and is associated with acquired resistance to targeted
therapies, including radiotherapy and chemotherapy. The
presentation described a Celldex-created humanized IgG1
Axl-targeting monoclonal antibody (mAb) that potently inhibits Gas6
binding and activation of Axl in tumor cell lines. The preclinical
candidate elicited a robust inflammatory response in human primary
myeloid cells via an FcR-dependent mechanism, leading to T cell
activation in mixed lymphocyte reactions. Administration of the
Axl-targeting mAb to tumor cells co-cultured with human PBMCs led
to dose-dependent killing of Axl-expressing tumor cells in vitro
and in vivo. The pleiotropic effects of Axl activation in cancer
support combination of Axl-targeting agents with other targeted
agents, either as drug combinations or as part of the same
molecule. To this end, Celldex has developed a prototype
tetravalent bispecific antibody combining PD-L1 and Axl targeting
that retains all the properties of the parental antibodies and
demonstrates enhanced activity in immune activation assays. Other
combinations are also under consideration and future efforts will
focus on the development of a multispecific molecule co-targeting
Axl with a second immune modulator.
CDX-527 Presentation Highlights
(Poster #406): CDX-527
is the first candidate from Celldex’s bispecific antibody platform.
It uses the Company’s proprietary highly active anti-PD-L1 and CD27
human antibodies to couple CD27 costimulation with blockade of the
PD-L1/PD-1 pathway to help prime and activate anti-tumor T cell
responses through CD27 costimulation, while preventing PD-1
inhibitory signals that subvert the immune response. In August
2020, Celldex initiated a multi-center Phase 1 dose-escalation
study in up to ~90 patients with advanced or metastatic solid
tumors that have progressed during or after standard of care
therapy to be followed by tumor-specific expansion cohorts. The
study is designed to determine the MTD during a dose-escalation
phase and to recommend a dose level for further study in the
subsequent expansion phase. The expansion is designed to further
evaluate the tolerability, and biologic and anti-tumor effects of
selected dose level(s) of CDX-527 in specific tumor types.
Enrollment is ongoing and initial data from the Phase 1 study are
anticipated in the first half of 2021.
KEYTRUDA® is a registered trademark of Merck Sharp & Dohme
Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ
USA.
About Celldex Therapeutics, Inc.Celldex is a
clinical stage biotechnology company dedicated to developing
monoclonal and bispecific antibodies that address devastating
diseases for which available treatments are inadequate. Our
pipeline includes antibody-based therapeutics which have the
ability to engage the human immune system and/or directly affect
critical pathways to improve the lives of patients with
inflammatory diseases and many forms of cancer. Visit
www.celldex.com.
Forward Looking Statement This 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; the effects of the
outbreak of COVID-19 on our business and results of operations; 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 cost of paying development, regulatory approval
and sales-based milestones under our merger agreement with Kolltan,
including the cost, timing, and outcome of our declaratory judgment
action against the Kolltan stockholder representative with respect
to certain of those milestones; 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; our ability to
continue to obtain 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; 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.
Company ContactSarah CavanaughSenior Vice
President, Corporate Affairs & AdministrationCelldex
Therapeutics, Inc.(781) 433-3161scavanaugh@celldex.com
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