Celldex Initiates ACT IV, a Pivotal International Phase 3 Trial of Rindopepimut in Patients with Glioblastoma
- Vaccine Targets Molecularly Defined Population- Patients with EGFRvIII-positive Glioblastoma -
NEEDHAM, Mass.--(BUSINESS WIRE)--Celldex Therapeutics, Inc. (NASDAQ: CLDX) today announced that it has launched a pivotal, randomized, double-blind, controlled Phase 3 trial of rindopepimut in patients with surgically resected epidermal growth factor variant III (EGFRvIII)-positive glioblastoma, the "ACT IV Study." US investigators have started screening patients for inclusion in the trial that is expected to enroll up to 440 patients internationally to recruit 374 patients with Gross Total Resection (GTR) for the primary analysis. Rindopepimut is a therapeutic cancer vaccine candidate that targets the tumor-specific oncogene EGFRvIII, which confers an enhanced capacity for unregulated tumor growth and which is present in many cancer cell types, but not present at significant levels in normal cells. Expression of EGFRvIII is linked to poor long term survival regardless of other factors such as extent of resection and age. EGFRvIII has been shown by polymerase chain reaction (PCR) analysis to be expressed in approximately 31% of glioblastoma tumors.
"Rindopepimut has demonstrated significant potential to offer a new treatment option to patients suffering from glioblastoma, a disease with an extremely poor prognosis and few treatment options"
"Rindopepimut has demonstrated significant potential to offer a new treatment option to patients suffering from glioblastoma, a disease with an extremely poor prognosis and few treatment options," commented Thomas Davis, M.D., Chief Medical Officer of Celldex. "Celldex has worked diligently with both US and European regulatory authorities to design the ACT IV trial to rigorously evaluate the addition of rindopepimut to standard of care in EGFRvIII-positive glioblastoma patients. This international Phase 3 study will be conducted in a blinded fashion, comparing rindopepimut against a control arm receiving only a low-dose of keyhole limpet hemocyanin (KLH). KLH is a component of rindopepimut and was selected due to its ability to generate a similar injection site reaction to that observed with the rindopepimut vaccine," added Dr. Davis.
"Given the consistent encouraging clinical data from multiple previous trials of rindopepimut showing clear improvements in median Overall Survival and median Progression Free Survival to both matched historical controls and historical data with the standard of care treatment, we look forward to expanding on this body of evidence in the pivotal ACT IV study," said Anthony Marucci, President and CEO of Celldex. "The initiation of ACT IV is an important milestone for Celldex and we expect to make substantial progress in this trial throughout 2012. We are also planning to further expand on the clinical development program for rindopepimut in 2011 by initiating the Phase 2 ReACT study of rindopepimut in combination with Avastin® in patients with recurrent or refractory glioblastoma."
About the ACT IV Study
The ACT IV study is a randomized, double-blind, controlled study of rindopepimut plus GM-CSF added to standard of care temozolomide in patients with newly diagnosed, surgically resected, EGFRvIII-positive glioblastoma. Patients will be randomized after the completion of surgery and standard chemoradiation. The treatment regime includes a vaccine priming phase post-radiation followed by an adjuvant temozolomide phase and a vaccine maintenance therapy phase. Patients will be treated until disease progression or intolerance to therapy. The primary objective of the study is to determine whether rindopepimut plus GM-CSF improves the overall survival of patients with newly diagnosed EGFRvIII positive glioblastoma after GTR when compared to treatment with the current standard of care, temozolomide. A total of approximately 440 patients will be enrolled at over 150 centers worldwide to recruit 374 patients with GTR to be included in the primary analysis. Secondary endpoints include: progression free survival; safety and tolerability of rindopepimut and GM-CSF in combination with temozolomide; neurologic status and quality of life. Patients will be stratified based upon geographic region, RPA class prognostic factors and MGMT methylation status.
Clinical Data Supporting Rindopepimut in Glioblastoma
Rindopepimut has been evaluated in three successful clinical studies of patients with EGFRvIII-positive glioblastoma to date: the ACTIVATE, ACT II and ACT III studies. Notably, rindopepimut demonstrated consistent and statistically significant increased survival rates across all three studies. In ACTIVATE, ACT II and ACT III, median progression free survival (PFS) from diagnosis was 14.2, 15.3 and 12.3 months, while median overall survival (OS) from diagnosis was 24.6, 24.4 and 24.6 months, respectively. The results were not statistically different between these studies. Mature data from the ACT III study were presented at the Society for Neuro-Oncology conference, indicating that 52% of the patients were alive at two years, while 50% of the enrolled patients in both earlier studies were alive at two years from diagnosis. These data compare favorably to a cohort of patients (historical controls) treated at M.D. Anderson Cancer Center and matched for eligibility including having glioblastoma expressing the EGFRvIII oncogene, where median PFS was 6.4 months and median OS was 15.2 months, with less than 6% of patients alive after 2 years. In addition, the four-year survival rate for ACTIVATE is 22%, while follow-up in ACT II and ACT III is ongoing.
In ACT III, the results for the predefined primary endpoint, 66% Progression Free Rate (PFR) at approximately 8.5 months post-diagnosis, show a statistically significant improvement (p=0.0168) over a predetermined estimate of 53%, which is beyond the range of expected progression-free survival for glioblastoma patients receiving standard of care (SOC). Published results for SOC and from matched historical controls are 45% and 29%, respectively, for PFR at 8.5 months post-diagnosis.
In all clinical trials to date, rindopepimut has been generally well tolerated with injection site reaction being the most frequently observed side effect.
Rindopepimut is an investigational immunotherapeutic vaccine that targets the tumor-specific molecule epidermal growth factor receptor variant III (EGFRvIII). EGFRvIII is a mutated form of the epidermal growth factor receptor (EGFR) that is only expressed in cancer cells and not in normal tissue and is a transforming oncogene that can directly contribute to cancer cell growth. Expression of EGFRvIII is linked to poor long term survival regardless of other factors such as extent of resection and age. EGFRvIII has been shown by polymerase chain reaction (PCR) analysis to be expressed in approximately 31% of glioblastoma tumors.
About Celldex Therapeutics, Inc.
Celldex Therapeutics is the first antibody-based combination immunotherapy company. Celldex has a pipeline of drug candidates in development for the treatment of cancer and other difficult-to-treat diseases based on its antibody focused Precision Targeted Immunotherapy (PTI) Platform. The PTI Platform is a complementary portfolio of monoclonal antibodies, antibody-targeted vaccines and immunomodulators used in optimal combinations to create novel disease-specific drug candidates. For more information, please visit http://www.celldextherapeutics.com.
Safe Harbor Statement Under the Private Securities Litigation Reform Act of 1995: 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 rindopepimut (CDX-110), CDX-011, CDX-1135 (formerly TP10), CDX-1401, CDX-1127, CDX-301, Belinostat and other products. 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 obtain additional capital on acceptable terms, or at all, including the additional capital which will be necessary to complete the clinical trials that we plan to initiate in 2011; our ability to adapt APC Targeting TechnologyTM to develop new, safe and effective vaccines against oncology and infectious disease indications; our ability to successfully complete product research and further development of our programs; the uncertainties inherent in clinical testing; our limited experience in bringing programs through Phase 3 clinical trials; our ability to manage research and development efforts for multiple products at varying stages of development; the timing, cost and uncertainty of obtaining regulatory approvals; the failure of the market for the Company's programs to continue to develop; our limited cash reserves and our ability to obtain additional capital on acceptable terms, or at all; 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 risks detailed from time to time in the Company's filings with the Securities and Exchange Commission, including the Company's Form 10-K for the fiscal year ended December 31, 2010, and its Forms 10-Q and 8-K.
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