Celldex Therapeutics' Phase 2 EMERGE Study of Glembatumumab Vedotin in Metastatic Breast Cancer Published in Journal of Clini...
April 06 2015 - 04:01PM
Celldex Therapeutics, Inc. (Nasdaq:CLDX) today announced that data
from the Phase 2 EMERGE study of glembatumumab vedotin in
metastatic breast cancer have been published in the Journal of
Clinical Oncology. The data from this study supported the
initiation of the ongoing, pivotal Phase 2 METRIC study in patients
with triple negative breast cancers that over-express glycoprotein
NMB (gpNMB). Glembatumumab vedotin is an antibody-drug conjugate
that targets and binds to gpNMB, a protein expressed by multiple
tumor types, including breast cancer. Overexpression of gpNMB has
been shown to promote the invasion and metastasis of cancer and has
been associated with poor clinical outcome.
"Previous studies of glembatumumab vedotin suggested that gpNMB
over-expression might correlate with the potential anti-cancer
activity of glembatumumab vedotin in breast cancer," said Thomas
Davis, MD, Executive Vice President and Chief Medical Officer of
Celldex Therapeutics. "We designed the EMERGE study to thoroughly
explore this hypothesis and observed impressive response rates and
prolonged survival in patients that over-expressed gpNMB on the
surface of their tumor cells. These data supported the initiation
of the METRIC study in patients with triple negative breast
cancer—where gpNMB over-expression is seen in approximately 40% of
patients. We believe gpNMB could be an important marker in breast
cancer and that glembatumumab vedotin holds significant potential
as a possible targeted therapy for women facing this disease."
EMERGE was a randomized, multi-center, controlled study. 124
patients with advanced, heavily pre-treated (2-7 lines of prior
chemotherapy including a taxane, an anthracycline, capecitabine,
and, if HER2-positive, trastuzumab and lapatinib) breast cancer
were enrolled and randomized (2:1) to receive glembatumumab vedotin
or "Investigator's Choice" (IC) single agent, approved
chemotherapy. The primary endpoint of the study was overall
response rate. Secondary endpoints included duration of response,
progression-free survival, overall survival, safety, and
pharmacokinetic and pharmacodynamic analyses. gpNMB expression
levels were evaluated via central immunohistochemistry on archived
tumor tissue.
Key findings:
- Glembatumumab was well tolerated in patients with
treatment-refractory breast cancer. The most common
treatment-related adverse events were nausea, rash, fatigue,
neuropathy, alopecia and neutropenia.
- Virtually all patients (99%) with breast cancer screened for
potential enrollment into the study expressed gpNMB at or greater
than 5%, the predefined expression level required for entry into
the study.
- A stratification and analysis explored whether intensity of
gpNMB expression in malignant epithelial (tumor) cell or stromal
tissues was associated with greater treatment effect and determined
that:
- Low or high expression in the stroma did not generally
correlate with outcome after glembatumumab vedotin, although there
was a trend towards increased PFS and OS for patients with high
stromal intensity.
- Patients whose tumors expressed higher levels of gpNMB in
malignant epithelial cells (>10 and >25%), had a
significantly greater likelihood of tumor response when compared
with all other pooled patients. No such correlation was seen in
patients treated with IC. Specifically, an ORR of 30% (7/23) was
observed for patients with >25% expression in malignant
epithelial cells as compared to 9% (1/11) on the IC arm. This was
also associated with improved progression-free survival and overall
survival. (PFS: 2.8 ms glembatumumab vs 1.5 ms IC; hazard ratio:
0.63; p=0.18. OS: 10.0 ms glembatumumab vs 5.7 ms IC; hazard ratio
0.67; p=0.31).
- In patients with triple negative breast cancer (TNBC), where
gpNMB is correlated with the metastatic phenotype and is more
frequently expressed, noteworthy activity was observed for
glembatumumab vedotin in patients with higher gpNMB expression
levels (>25% gpNMB expression in malignant epithelial cells),
with an ORR of 40% (4/10) for the glembatumumab vedotin arm and 0%
(0/6) for the IC arm. An improvement in PFS and OS was also noted
(PFS: 3.5 ms glembatumumab vs 1.5 ms IC; hazard ratio 0.11;
p=0.0017. OS: 10.0 ms glembatumumab vs 5.5 ms IC; hazard ratio
0.14; p=0.003).
About Glembatumumab Vedotin
Glembatumumab vedotin (CDX-011) is a fully-human monoclonal
antibody-drug conjugate (ADC) that targets glycoprotein NMB
(gpNMB). gpNMB is a protein overexpressed by multiple tumor types,
including breast cancer and melanoma. gpNMB has been shown to be
associated with the ability of the cancer cell to invade and
metastasize and to correlate with reduced time to progression and
survival in breast cancer. The gpNMB-targeting antibody, CR011, is
linked to a potent cytotoxic, monomethyl auristatin E (MMAE), using
Seattle Genetics' proprietary technology. Glembatumumab vedotin is
designed to be stable in the bloodstream, but to release MMAE upon
internalization into gpNMB-expressing tumor cells, resulting in a
targeted cell-killing effect. Glembatumumab vedotin is in
development for the treatment of locally advanced or metastatic
breast cancer, with an initial focus in triple negative disease,
and for the treatment of Stage III and IV melanoma. Additional
studies are planned in squamous cell lung cancer, osteosarcoma,
uveal melanoma and pediatric sarcoma.
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.
Celldex 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; 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
our 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: Celldex Company Contacts:
Investors:
Sarah Cavanaugh
Vice President of Investor Relations &
Corp Communications
Celldex Therapeutics, Inc.
(781) 433-3161
scavanaugh@celldex.com
or
Media:
Dan Budwick
Pure Communications, Inc.
(973) 271-6085
dan@purecommunicationsinc.com
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