Celldex Therapeutics Announces EGFRvIII Vaccine Data In Glioblastoma Multiforme

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Dr. John Sampson presented data from the Phase 2 ACTIVATE trial and ACT II continuation study of CDX-110, an immunotherapy that targets the tumor specific molecule EGFRvIII.

The clinical trial studied in patients with newly diagnosed glioblastoma multiforme that are EGFRvIII positive.

The ACTIVATE study currently shows a median survival time of 126.1 weeks, or almost 2.5 years, as well as a median time-to-progression of 64.5 weeks (p=0.0001) versus the historical control's median of 28.52 weeks. ACT II has not reached median time-to- progression or survival, but preliminary findings indicate that chemotherapy and CDX-110 can be administered concurrently without diminishing the induced immune responses.

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In the ACTIVATE trial, 23 patients with newly diagnosed glioblastoma who tested positive for EGFRvIII received radiation and temozolomide (TMZ) (75 mg/m2) concurrently, followed by vaccination with CDX-110. The current median survival data of 126.1 weeks compares favorably with the published results of Gliadel (59.6 weeks, Westphal et al, 2003) and Temodar (58.4 weeks, Stupp et al, NEJM 2005).

In ACT II, the ACTIVATE continuation study, 14 patients received the same concurrent radiation and TMZ, but received their vaccination on day 21 of repetitive 28-day TMZ cycles (200 mg/m2). These interim results show that EGFRvIII-specific CD3+CD8+gamma-IFN producing T-cells induced by CDX-110 vaccination do not appear to be diminished during cycles of concurrently administered TMZ. Both chemotherapy and CDX-110 can be delivered concurrently without negating the effects of the immunotherapy. TMZ-induced lymphopenia may prove to be synergistic with a peptide vaccine like CDX-110.

"CDX-110 has the potential to be a breakthrough treatment for patients with glioblastoma," said Thomas Davis, M.D., Chief Medical Officer of Celldex Therapeutics. "These updated clinical data provided at ASCO revealed two significant findings: a truly significant median survival figure from the open-label Phase 2a trial that more than doubles that observed through the use of two FDA-approved products, and data demonstrating that giving appropriately-timed chemotherapy can enhance immune responses from the CDX-110 vaccine. We recently initiated and are currently enrolling our Phase 2/3 ACT III clinical trial, which will evaluate CDX-110 in 90 patients at over 20 brain tumor centers across North America."

CDX-110 is an 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 Dr. Bert Vogelstein and Dr Albert Wong at Johns Hopkins University and Dr. Darell Bigner at Duke University. 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

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