Celldex Therapeutics, Inc. (NASDAQ:CLDX) today presented positive,
mature results from the Company's Phase 2 study of glembatumumab
vedotin in patients with stage III/IV checkpoint
inhibitor-refractory, and, if applicable, BRAF/MEK
inhibitor-refractory metastatic melanoma (n=62). Glembatumumab
vedotin is a fully human monoclonal antibody-drug conjugate (ADC)
that targets glycoprotein NMB (gpNMB), a protein overexpressed by
multiple tumor types, including metastatic melanoma, where more
than 80% of patients overexpress the marker. High tumor expression
of gpNMB is associated with shorter metastasis-free survival and
reduced overall survival.1 Study results were presented today in an
oral presentation by Patrick A. Ott, M.D., Ph.D., Clinical Director
of Dana-Farber Cancer Institute's Melanoma Center and its Center
for Immuno-Oncology, Assistant Professor of Medicine at Harvard
Medical School and an investigator in the study, at the 2017
American Society of Clinical Oncology (ASCO) Annual Meeting in
Chicago.
Study Highlights
- Median overall survival (OS) for all patients was 9.0 months
(95% CI: 6.1, 13.0).
- As previously reported in October 2016, 7 of 62 (11%) patients
experienced a confirmed response, and an additional three patients
also experienced single timepoint partial responses. Since data
were reported in October, one patient converted from a confirmed
partial response to a confirmed complete response.
- Patients who experienced rash in Cycle 1 experienced a more
prolonged OS with a median of 15.8 months (p=0.026, HR=0.44) as
compared to those who did not experience rash.
"It’s exciting to see clinical activity in this study as very
few treatment options exist for melanoma patients who progress
after immune checkpoint inhibitors and BRAF targeted therapy," said
Dr. Ott. "The single-agent response rate observed in this study,
including a complete response, and the duration of the objective
responses continue to suggest that glembatumumab vedotin is an
active agent in this disease. I am hopeful that leveraging the
immune system with checkpoint inhibition in combination with the
cytotoxic and immunologic cell death induced by glembatumumab
vedotin could bring benefit to an even larger number of patients
with melanoma, and I look forward to the outcome of these
additional cohorts."
Phase 2 Study Single-agent Cohort Overview and
Previously Presented Results
Patients enrolled in this single-agent, open-label cohort of
glembatumumab vedotin presented with unresectable stage IV (n=62)
melanoma. The median number of prior therapies was three (range of
1 to 8). All patients had been heavily pre-treated and had
progressed during or after checkpoint inhibitor therapy, and almost
all patients had received both ipilimumab (n=58; 94%) and
anti-PD-1/anti-PD-L1 (n=58; 94%) therapy. Twelve patients presented
with BRAF mutation, and fifteen had prior treatment with BRAF or
BRAF/MEK targeted agents. Patients received glembatumumab vedotin
every three weeks until disease progression or intolerance. The
safety profile was consistent with prior studies of glembatumumab
vedotin with rash, neutropenia and neuropathy experienced as the
most significant adverse events.
As previously reported, the primary endpoint of the cohort (6 or
more objective responses in the first 52 patients enrolled) was
exceeded. Seven of 62 (11%) patients experienced a confirmed
response, and an additional three patients also experienced single
timepoint responses. The median duration of response was 6.0
months. A 52% disease control rate (patients without progression
for greater than three months) was demonstrated, and median PFS for
all patients was 4.4 months. Consistent with previous studies in
melanoma and breast cancer, rash was associated with greater
clinical benefit. Patients who experienced rash in Cycle 1
experienced a 21% confirmed response rate, a more prolonged PFS
with a median of 5.5 months (p=0.006; HR=0.39) and a more prolonged
OS with a median of 15.8 months (p=0.026, HR=0.44).
Pre-treatment tumor tissue was available for 59 patients. All
samples were gpNMB positive, and 78% of patients had tumors with
100% of their epithelial cells expressing gpNMB. Given both the
high level of expression and the intensity of expression across
this patient population, identifying a potential population for
gpNMB enrichment is not feasible; therefore, all patients with
metastatic melanoma could be evaluated as potential candidates for
treatment with glembatumumab vedotin in future studies.
Ongoing Cohorts Combining Glembatumumab Vedotin with
Varlilumab or Checkpoint Inhibitor
In August 2016, the Company announced that the study protocol
was amended to add a second cohort of patients to a glembatumumab
vedotin and varlilumab combination. Varlilumab is Celldex's fully
human monoclonal agonist antibody that binds and activates CD27, a
critical co-stimulatory molecule in the immune activation cascade.
This additional cohort has completed enrollment with data
presentation expected in the fall of 2017. Celldex is now enrolling
patients to a third arm in the study to assess a glembatumumab
vedotin and checkpoint combination in patients who have previously
progressed on checkpoint inhibitor. This rationale is strongly
supported by preclinical data that suggest that the anti-tumor
activity may be enhanced with the combination. In addition, due to
their direct cytotoxic properties, microtubule-depolymerizing
agents like MMAE also appear to convert tumor-resident tolerogenic
dendritic cells into active antigen-presenting cells.2
The Company also intends to conduct exploratory analyses of
pre-entry skin biopsies in future patients to investigate potential
predictors of response to glembatumumab vedotin, given the
association of rash and outcome.
About Glembatumumab Vedotin
Glembatumumab vedotin 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, melanoma, lung cancer, uveal melanoma and osteosarcoma.
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, stage III and IV melanoma,
squamous cell lung cancer and uveal melanoma.
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 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 integrate the business and programs of Kolltan with
our business and programs; our ability to successfully complete
research and further development and commercialization of
glembatumumab vedotin and other 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; 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 Fast Track designation for glembatumumab
vedotin 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.
References 1. Rose, et al. Clin Cancer Res.
2010; 16(7):2147-56. 2. Müller, et al. Cancer Immunol. Res. 2014;
2(8):741-55.
Company Contact
Sarah Cavanaugh
Vice President of Investor Relations & Corp Communications
Celldex Therapeutics, Inc.
(781) 433-3161
scavanaugh@celldex.com
Charles Liles
Associate Director of Investor Relations & Corp Communications
Celldex Therapeutics, Inc.
(781) 433-3107
cliles@celldex.com
Media Contact
Dan Budwick
Founder, 1AB Media
(973) 271-6085
dan@1abmedia.com
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