Celldex Therapeutics Reports Positive Mature Survival Data from Rindopepimut Phase 2 Brain Cancer Study at SNO 2011

Celldex Therapeutics Reports Positive Mature Survival Data from Rindopepimut Phase 2 Brain Cancer Study at SNO 2011

-- Randomized International Phase 3 Trial to Initiate in 2011 --

NEEDHAM, MA (November 21, 2011): Celldex Therapeutics, Inc. (NASDAQ: CLDX) today announced the presentation of mature overall survival (OS) data for ACT III, a multi-center, single arm, Phase 2 clinical trial of rindopepimut (CDX-110) in patients with newly diagnosed EGFRvIII-positive glioblastoma (GB). The data showed a final median OS of 24.6 months from diagnosis, which is significantly better than 15.2 months for a historical cohort of patients selected to match ACT III eligibility criteria. The median OS data obtained from the 31 centers participating in the ACT III study are very consistent with two previous smaller studies with rindopepimut in GB (ACTIVATE and ACT II) conducted at M.D. Anderson and Duke University which showed 24.6 and 24.4 month median OS, respectively. These data were described in an oral presentation at the 16th Annual Meeting of The Society for Neuro-Oncology (SNO) in Orange County, CA by the lead investigator on the study, Dr. Rose Lai.

Previously published retrospective analysis has documented that expression of the EGFRvIII oncogene correlates with poor long term survival. In ACT III, the two-year survival rate was 52% and compares very favorably with 6% for the matched EGFRvIII-positive historical cohort. The two-year survival data in ACT III is also consistent with the two prior studies which showed 50% survival at two years. In addition, data from ACTIVATE and ACT II have shown that approximately 20% of patients from each study continue treatment with durations of 6-8 years on study.

"These data continue to suggest that rindopepimut is extending survival well beyond what we have seen historically in this EGFRvIII patient population," said Rose Lai, M.D., Assistant Professor of Neurology, University of Southern California, and lead investigator on the ACT III study.

"The consistency of data from three separate studies, including a large multicenter trial, is very encouraging and clearly supports our plan to advance clinical development of rindopepimut with ACT IV, a pivotal, randomized, blinded international Phase 3 study," said Thomas Davis, M.D., Chief Medical Officer of Celldex Therapeutics.

Summary of Results for Rindopepimut Studies

Median OS from diagnosis (months)

OS at

24 Months

Median PFS from diagnosis (months)

ACT III (n=65)

24.6

52%

  12.3x

ACT II (n=22)

24.4

50%

15.3

ACTIVATE (n=18)

24.6

50%

14.2

Matched historical control (n=17)#

15.2

 6%

 6.4

Standard of care radiation/TMZ+ (n=287)

14.6

27%

 6.9

 

 

 

 

x Change in median PFS not statistically significant from ACTIVATE and ACT II.

# Sampson, et al. J Clin Oncol. 2010 Nov 1;28(31):4722-9. 

  Historical controls were treated at M.D. Anderson and matched for eligibility (EGFRvIII-positive, KPS ≥ 80%, complete resection, radiation/TMZ and without progression through ~ 3 months post-diagnosis).

+ Stupp, et al. N Engl J Med 2005;352:987-96.

Rindopepimut is an investigational immunotherapeutic vaccine that targets the tumor-specific oncogene, epidermal growth factor receptor variant III (EGFRvIII). The multi-center Phase 2 trial enrolled 65 patients with newly-diagnosed and optimally resected EGFRvIII-expressing GB. About 3 months post-diagnosis and following treatment with standard chemoradiation, patients started vaccination with rindopepimut in combination with standard of care (SoC) temozolomide therapy. 

The results for the predefined primary endpoint (66% Progression Free Rate or “PFR” at approximately 8.5 months post-diagnosis) show a statistically significant improvement (p=0.0168, 95% CI) over a predetermined estimate of 53%, which was a high estimate derived from published results for standard chemoradiation with temozolomide (45%) and a cohort of patients with tumors expressing the EGFRvIII oncogene selected to match major ACT III eligibility criteria (29%).

Median OS was 24.6 months from diagnosis, which is significantly better than the matched EGFRvIII positive cohort (15.2 months). OS at 24 months was 52% compared with 6% for the matched EGFRvIII positive cohort. The apparent PFS and OS benefit was seen in both temozolomide sensitive (MGMT methylated) patients as well as temozolomide resistant (MGMT unmethylated) patients.

Robust, specific and durable anti-EGFRvIII immune responses were generated, and the high level of immunity seen in vaccinated patients is again associated with loss of EGFRvIII at recurrence. Rindopepimut was generally well-tolerated with treatment duration up to more than seven years; toxicities consisted chiefly of injection site reactions, while fatigue, rash, nausea and pruritus also occurred in >10% of patients. Activity and safety data are very consistent with previous smaller studies of rindopepimut in GB conducted at M.D. Anderson and Duke University (ACTIVATE and ACT II).

About Rindopepimut

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 expressed in 31% of GB tumors when assessed using the Celldex PCR assay.

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  HYPERLINK "http://www.celldextherapeutics.com" 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

 

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