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UPDATED CDX-110 DATA IN
GLIOBLASTOMA MULTIFORME
PRESENTED AT 44th ANNUAL ASCO ANNUAL MEETING
Survival and Time-to-Progression Reported From
CHICAGO June 2, 2008 AVANT
Immunotherapeutics (Nasdaq: AVAN) and Pfizer, Inc. (NYSE: PFE) today
announced the presentation of new data from two Phase 2 studies at the 44th
Annual Meeting of the American Society of Clinical Oncology (ASCO) for CDX-110,
an investigational immunotherapeutic vaccine that targets the
tumor-specific molecule epidermal growth factor receptor variant III
(EGFRvIII). CDX-110 was generally well-tolerated with
primary toxicity reported as local injection site reactions.
Included in the presentation were updated data from
the Phase 2 ACTIVATE trial (n=21) and the continuation study, ACT II (n=23) of
CDX-110 in patients with newly diagnosed EGFRvIII-positive glioblastoma
In the ACTIVATE study, median survival time was 26 months (95% CI: 21.6,
infinity) and median time-to-progression (TTP) was 14.2 months. Median survival
in a historical matched cohort was 15.2 months (17/17) (95% CI: 13.9,
20.5).(p=0.0001) with median time to progression of 7.13 months (p=0,0001). (1) No
significant adverse events were seen in this study.
Preliminary results from the ACT II study currently estimate median overall survival to be 33.1 months,
(1) Heimberger, A., et al. Epidermal
Growth Factor Receptor VIII Peptide Vaccination Is Efficacious Against
Established Intracerebral Tumors. Clin Cancer Res Vol. 9,
pp4247-4254, September 15, 2003.
although the median has not yet been
reached. The survival of a matched
historical control group was 14.3 months (95% CI: 13.0, 16.2) and a subgroup
treated with temozolomide (TMZ) of 15.2 months (95% CI: 13.9, 20.5 p=0.0078).
Overall TTP was 16.6 months (95% CI: 10.8, infinity) compared with 6.4 months
for the historical control group (95% CI: 5.0, 14.1). In this study, primary
toxicity was reported as local injection site reactions.
Vaccination with CDX-110 together with standard of
care temozolomide in patients with glioblastoma multiforme increased time to
progression and overall survival compared with a matched historical control
group in these Phase 2 studies, said John Sampson, M.D., Associate Professor
of Neurosurgery at Duke University Medical Center, who presented the data.
This is encouraging news for patients with this specific type of brain tumor,
who are currently facing very limited treatment options. This treatment is
being further studied in a randomized Phase 2b/3 trial to confirm these
The ACTIVATE trial studied CDX-110 vaccine in 21
patients with newly-diagnosed EGFRvIII-expressing GBM who had undergone
surgical (gross-total) resection followed by conformal radiation therapy with
concurrent oral temozolomide (75 mg/m(2) per day) without tumor
progression. CDX-110 mixed with granulocyte-macrophage colony stimulating
factor (GM-CSF) (142 mcg) was administered intradermally. Sixteen patients
received CDX-110 at two week intervals for three doses, while five patients
received saline in a blinded fashion for the first three vaccinations.
Thereafter, all patients received monthly CDX-110 injections mixed with GM-CSF
until tumor progression. Safety was assessed through evaluation of adverse
events, complete physical and neurological exams, and routine clinical
The ACT II study enrolled a total of 23 patients.
The patient population and treatment scheme were similar to ACTIVATE, except
that no early placebo was given and two dose schedules of maintenance
temozolomide were studied (13 patients received 200 mg/m(2) daily times
five every 28 days, while 10 received 100 mg/m(2) daily times 21 days
every 28 days for a maximum of 12 cycles),.Monthly CDX-110
vaccination mixed with GM-CSF was given on day 21 of
each cycle until tumor progression. Safety was assessed in a similar fashion to
is a mutated form of epidermal growth factor receptor (EGFR) that is only
expressed in cancer cells and not in normal tissue(2) and is a
transforming oncogene that can directly contribute to cancer cell growth, as it
does in about 40 percent of GBM tumors.(3),(4),(5)
is currently enrolling the Phase 2b portion of a Phase 2b/3 clinical trial
called ACT III, which is evaluating CDX-110 in 90 patients at over 20 cancer
centers across North America. The Phase 3 portion will not open until data is
available from Phase 2b and pending further discussions with FDA.
investigational immunotherapy that targets the tumor specific molecule
EGFRvIII, a functional variant of the epidermal growth factor receptor (EGFR),
which is a protein that has been well validated as a target for cancer therapy.
This particular variant, EGFRvIII, was discovered in a collaborative effort
between Bert Vogelstein, M.D. and Bigner, M.D., at Duke University. Application
of this discovery toward the development of the CDX-110 vaccine was further
advanced by Dr. John Sampson, M.D. and his colleagues at the Duke
University Brain Tumor Center in collaboration with Amy Heimberger, M.D. at the
M.D. Anderson Cancer Center. Unlike EGFR, EGFRvIII is not present in normal
tissues, suggesting this target will enable the development of a tumor-specific
therapy for cancer patients. Furthermore, EGFRvIII is a transforming oncogene
that can directly contribute to cancer cell growth. While originally discovered
in GBM, the most common and aggressive form of brain cancer, the expression of
EGFRvIII has also been observed in various tumors such as
C, et al. Mutant Epidermal Growth Factor Receptor (EGFRvIII)
Contributes to Head and Neck Cancer Growth and Resistance to EGFR Targeting Clin
Cancer Res; 12(17) Sept.1, 2006
A., et al. Prognostic Effect of Epidermal Growth Factor Receptor
and EGFR vIII in Glioblastoma Multiforme Patients Clin Cancer Res
Vol 11, p.1462 February 15, 2005
M., et al. Effect of Epidermal Growth Factor on Glioma Cell
Growth, Migration, and Invasion In Vitro. Cancer Res 50, p. 6039
C, et al. Cell Surface Localization and Density of
theTumor-Associated Variant of the Epidermal Growth Factor Receptor, EGFRvII Cancer
Res 57, p.4130, September 15 1997
breast, ovarian, metastatic
prostate, colorectal, and head & neck cancers. Celldex owns the rights
to EGFRvIII vaccines and is pursuing the development of CDX-110 for GBM
therapy, as well as in other cancers through additional clinical studies.
April 16, 2008, Pfizer, Inc. and Celldex Therapeutics, a wholly-owned
subsidiary of AVANT Immunotherapeutics, entered into an agreement that granted