Celldex Therapeutics Initiates Phase 1/2 Study of Varlilumab in Combination with Atezolizumab in Renal Cell Carcinoma
December 08 2015 - 8:59AM
Celldex Therapeutics, Inc. (NASDAQ:CLDX) today announced the
initiation of an open-label, Phase 1/2 safety and tolerability
study examining the investigational combination of varlilumab and
Roche's atezolizumab (MPDL3280A) in patients with unresectable
stage III or IV renal cell carcinoma (RCC). Celldex previously
announced the collaboration with Roche to evaluate the novel
immunotherapy combination in March 2015. Under the terms of the
agreement, Roche will provide atezolizumab, and Celldex will be
responsible for conducting and funding the study. Varlilumab is
currently being studied in five Phase 1/2 combination studies.
Varlilumab is Celldex's fully human monoclonal agonist antibody
that binds and activates CD27, a critical co-stimulatory molecule
in the immune activation cascade. Atezolizumab is designed to
target PD-L1 expressed on tumor cells and tumor-infiltrating immune
cells, preventing PD-L1 from binding to PD-1 and B7.1 on anti-tumor
T cells. By inhibiting PD-L1, atezolizumab may enable the
activation of anti-tumor T cells. These two antibodies are part of
a new class of investigational medicines known as cancer
immunotherapies. They are designed to harness the body's own immune
system to fight cancer through separate yet complementary
mechanisms of action that may enable the activation of T cells,
restoring their ability to effectively detect and attack tumor
cells.
Data from multiple preclinical tumor models suggest the
combination of these two mechanisms are synergistic and enhance
anti-tumor immune response compared to either agent alone. Also, in
a Phase 1 study of varlilumab in multiple solid tumors, promising
signs of clinical activity in patients with refractory RCC were
observed, including a durable partial response (duration of
response = 13.6+ months) that continued to decrease in tumor volume
over time and prolonged stable disease (four patients with a range
of 5.3 to 36.2+ months).
"Together, preclinical and clinical data suggest that combining
varlilumab and atezolizumab may enhance anti-tumor immune responses
compared to monotherapy," said Thomas Davis, M.D., Executive Vice
President and Chief Medical Officer of Celldex Therapeutics.
"Varlilumab is an attractive candidate for combination
immunotherapy across a variety of cancers due to its target's
restricted expression and strong activity in a variety of tumor
models, as well as positive data and a favorable safety profile
from our Phase 1 study."
Study Design
Phase 1 study portion
The Phase 1, dose-escalation portion of the study will assess
the safety and tolerability of varlilumab at 0.3, 1.0 and 3.0 mg/kg
combined with atezolizumab at 1200 mg in order to identify a
recommended dose for the Phase 2 portion of the study. The Phase 1
portion will enroll patients with unresectable stage III or IV
melanoma, RCC, triple negative breast cancer, bladder cancer, head
and neck cancer or non-small cell lung cancer (NSCLC).
Phase 2 study portion
The Phase 2 portion of the study will enroll patients with RCC.
The primary objective of this portion of the study is to assess the
preliminary anti-tumor efficacy of the varlilumab/atezolizumab
combination measured by objective response rate (ORR). Secondary
objectives include safety and tolerability, pharmacokinetics,
immunogenicity and further assessment of anti-tumor activity across
a broad range of endpoints.
In total, the Phase 1/2 study is anticipated to include up to 10
sites in the United States and enroll approximately 60 patients. In
each 12-week cycle for both phases of the trial, varlilumab and
atezolizumab will be administered once every three weeks (four
doses). Patients will be treated with varlilumab until intolerance,
disease progression or completion of up to 4 cycles. There is no
limit on the duration of treatment with atezolizumab.
About Varlilumab
Varlilumab is a fully human monoclonal agonist antibody that
binds and activates CD27, a critical co-stimulatory molecule in the
immune activation cascade. CD27 can be effectively manipulated with
activating antibodies to induce potent anti-tumor responses and may
result in fewer toxicities due to its restricted expression and
regulation. Varlilumab is a potent anti-CD27 agonist that induces
activation and proliferation of human T cells when combined with T
cell receptor stimulation. In lymphoid malignancies that express
CD27 at high levels, varlilumab may have an additional mechanism of
action through a direct anti-tumor effect. Varlilumab has completed
a Phase 1 dose-escalation study, demonstrating potent immunologic
activity consistent with its mechanism of action and anti-tumor
activity in patients with advanced, refractory disease. No maximum
tolerated dose was reached and minimal toxicities were observed.
Celldex has initiated a broad development program for varlilumab to
explore its role as an immune activator in combination with a
number of complementary investigational and approved oncology
drugs.
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.
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, including those related to the Company's
strategic focus and the future development and commercialization
(by Celldex and others) of RINTEGA® ("rindopepimut"; "rindo";
CDX-110), glembatumumab vedotin ("glemba"; CDX-011), varlilumab
("varli"; CDX-1127), CDX-1401, CDX-301 and other products and our
goals for 2015. 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 RINTEGA, 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 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; our ability to maintain and
derive benefit from the Breakthrough Therapy Designation for
RINTEGA, which does not change the standards for regulatory
approval or guarantee regulatory approval on an expedited basis, or
at all; 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.
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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