Significant Tumor-Specific Immune Response Observed in AVANT's Phase 2 Trial Evaluating CDX-110 with Temozolomide for Treatment of Glioblastoma Multiforme
Tuesday April 15, 4:05 pm ET
- New Data Subject of Late-Breaking Presentation at American Association for Cancer Research Meeting -
NEEDHAM, Mass.--(BUSINESS WIRE)--Celldex Therapeutics (a wholly-owned subsidiary of AVANT Immunotherapeutics, Nasdaq: AVAN) announced today that new data from the Phase 2 ACT II study in glioblastoma multiforme (GBM) suggest that temozolomide, the standard chemotherapy agent for this disease, may potentiate the effect of AVANT’s vaccine candidate CDX-110. These data were presented in a late-breaking presentation at the annual meeting of the American Association for Cancer Research (AACR) in San Diego, California.
All patients vaccinated with CDX-110 in the Phase 2a ACT II extension study showed a tumor-specific immune response, a significant improvement over previous vaccines and over CDX-110 alone. Patients vaccinated in conjunction with the daily temozolomide (TMZ) dose had a statistically significant increase in anti-EGFRvIII antibody titers (P=0.028) compared to patients that received the standard 200 mg/m2 dose of TMZ. In addition, the Delayed Type Hypersensitivity response (DTH) following vaccination was also greater in the patients receiving the continuous 21 day TMZ dose (P=0.05). Early Time to Progression (TTP) and Overall Survival (OS) data also look very promising. Contrary to conventional scientific expectation, these data suggest that chemotherapy enhances the induction of a vaccine specific immune response, and that daily chemotherapy may further enhance the vaccine’s effect.
“These fascinating results may represent a new paradigm in tumor vaccine therapy,” said John Sampson, M.D., a Neurosurgeon at Duke University and the lead investigator of the study. “If we can combine the tumor killing effect of chemotherapy with an enhanced effect from tumor specific immunotherapy, we may be entering a new era for GBM treatment.” Tom Davis, AVANT’s Chief Medical Officer, added, “We are very pleased to see ongoing data confirm our belief that CDX-110 plus TMZ may improve the prognosis for patients with GBM and expect to present survival data from this study at ASCO in June. We also eagerly await the data from AVANT’s currently enrolling randomized Phase 2b/3 study, ACT III, which is designed to confirm the Phase 2a results.”
The Study
Dr. John Sampson and colleagues have previously generated data in the Phase 2a ACTIVATE study suggesting that the CDX-110 vaccine given alone in the adjuvant setting could lead to a doubling of survival in patients with newly diagnosed, resected GBM that expresses EGFRvIII, a proprietary tumor specific variant of the EGFR protein. Traditional scientific thought would suggest that chemotherapy, particularly if given daily, would undermine the effect of a vaccine. Based upon preclinical data suggesting that temozolomide (TMZ), a standard treatment for GBM, might actually improve the effect of CDX-110, Dr. Sampson enrolled 21 patients in the ACT II study. Patients received CDX-110 along with adjuvant temozolomide on either a monthly or daily regimen, and were followed for immune responses, Time to Progression (TTP) and Overall Survival (OS).
About the CDX-110 Vaccine
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 oncogene that can directly contribute to cancer cell growth. While originally discovered in Glioblastoma Multiforme (GBM), the most common and aggressive form of brain cancer, the expression of EGFRvIII has also been observed in various other cancers such as breast, ovarian, metastatic prostate, colorectal, and head & neck malignancies. AVANT has exclusive worldwide 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. |
