CDX-110 : Clinical Program
Clinical Program for Malignant Glioblastoma
CDX-110 is an immunotherapy that targets the tumor specific molecule called EGFRvIII, a functional variant of the epidermal growth factor receptor (EGFR), a protein that has been well validated as a target for cancer therapy. 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 the 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 cancers. Celldex is pursuing the development of CDX-110 for GBM therapy, as well as in other cancers through additional clinical studies.
A summary of the clinical program with CDX-110 is presented below. Initial clinical development of EGFRvIII immunotherapy was led by collaborating investigators at the Brain Tumor Center at the Duke Comprehensive Cancer Center and at the M.D. Anderson Cancer Center in Houston, Texas. The results from Phase 1 and Phase 2 studies have demonstrated a significant increase in the time to disease progression (>100%) post vaccination, and also in overall survival (approx. 1 year) – both relative to appropriately matched historical controls. The therapy has been well tolerated, and significant immune responses to EGFRvIII were generated. The only frequently observed side effect was inflammation at the site of injection. Importantly, 20/23 relapsed tumors that were biopsied were found to no longer have significant EGFRvIII expression - suggesting a potent immune rejection of EGFRvIII expressing tumor cells. In collaboration with our partner, Pfizer, Celldex is currently performing a Phase 2/3 randomized, controlled study of CDX-110 combined with standard of care vs. standard of care alone in patients with newly diagnosed GBM.
CDX-110 Clinical Programs Summary
| Currently Enrolling | |
| Phase 2/3: Newly Diagnosed Glioblastoma Multiforme (GBM) with EGFRvIII Expression | |
| Design: | Randomized, multi-institution study with standard of care control arm. Adequate Phase 2 data (an improvement in 6 month PFS of at least 7%), will trigger continued Phase 3 accrual. |
| Status: | Currently enrolling in multiple centers across North America |
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| Previous Clinical Study | |
| Phase 2: Newly Diagnosed Glioblastoma Multiforme (GBM) with EGFRvIII Expression | |
| Design: | Single arm with matched historical controls; two centers (Duke, MDACC). |
| Status: | 45 patients enrolled into 2 cohorts: CDX-110 vaccine alone (the ACTIVATE Study) or CDX-110 plus temozolomide (The ACT II Study). The vaccine has been well tolerated without evidence of induced autoimmunity. Robust humoral immune responses were generated. When compared to matched historical controls, both TTP and Overall Survival appear to be significantly improved. For more details CLICK HERE |
CDX-110 : Currently enrolling to act III Phase 2/3
Study Title: A Phase 2/3 Randomized Study of CDX-110 with Radiation and Temozolomide in Patients with Newly Diagnosed Glioblastoma Multiforme
About the Clinical Trial
This research study will investigate the anticancer activity, impact on survival, and safety of the addition of CDX-110 vaccine to standard of care maintenance chemotherapy (with temozolomide) with radiation in patients with glioblastoma multiforme.
Enrolled patients will be randomly assigned to receive either standard of care maintenance chemotherapy with radiation, or standard of care plus intradermal injections of CDX-110 on a biweekly to monthly basis, continuing until progression of disease. The randomization will be imbalance, meaning that 2 patients will be randomized to the vaccine arm for every patient randomized to the standard of care arm.
This Phase 2/3 study will be conducted in two stages. Approximately 90 patients will participate in the Phase 2 portion, and if results show an improvement in disease-free survival for the CDX-110 treated patients, an additional 285 participants will be enrolled in the Phase 3 portion.
Patient Eligibility
Major entry criteria include:
- Newly diagnosed glioblastoma multiforme which expresses EGFRvIII (screening is included in pre-study evaluation) in patients 18 years of age or older.
- Previous successful gross tumor resection (less than 1 cm2 residual disease)
- No disease progression after chemoradiation
For more information on enrollment and open clinical trial sites, please contact Celldex Therapeutics at (908) 454-7120 extension 305 or click here for up-to-date information on the study.
