CDX-110 : Clinical Programs

Our Lead Clinical Program for Malignant Glioblastoma

Our lead clinical development program, 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.

EGFRvIII Expression in Various Human Tumors

Cancer Type	US New Cases/Yr	%Positive
GBM	10,000	~45%
Ovarian	25,000	~52%
Breast	215,000	~56%
Prostate	234,000	35-95%
Head & Neck	55,000	~42%
Colorectal	107,000	~56%

A summary of the clinical programs 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 I and phase II studies (16 and 23 patients, respectively) have demonstrated a significant increase in the time to disease progression (>113%) in the vaccinated cohort, and also in overall survival rates (>53%) – both relative to appropriately matched historical controls. The therapy has been well tolerated, and significant immune responses to EGFRvIII were generated. The only observed side effects were mild reddening at the site of injection. Importantly, 6/6 relapsed tumors were found to have lost EGFRvIII expression - suggesting a potent immune rejection of EGFRvIII expressing tumor cells. Independently, active immunotherapy for EGFRvIII in prostate and ovarian cancer patients is being conducted in a phase I trial at the University of Washington.

Celldex will initiate a phase II/III randomized study of CDX-110 combined with standard of care vs. standard of care in patients with GBM in early 2007.

CDX-110 Clinical Programs Summary

 

Currently Enrolling:
Phase II/III: Newly Diagnosed Glioblastoma Multiforme (GBM) with EGFRvIII Expression
Design:	Randomized, multi-institution study with standard of care control arm. Interim analysis after phase II by independent monitoring board.
Status:	Initiation of enrollment planned for early 2007.
Ongoing Clinical Studies:
Phase II: Newly Diagnosed Glioblastoma Multiforme (GBM) with EGFRvIII Expression
Design:	Single arm with matched historical controls; two centers (Duke, MDACC).
Status:	23 Patients enrolled, Well tolerated and without evidence of autoimmunity. Humoral and cellular immune responses were generated. Median TTP from surgery in treated patients is 12 months (n=12), comparing favorably with a historical matched untreated cohort that had a median TTP of 7.1 months (n=39)(p=0.0058). Median survival in this trial has exceeded 18 months which compares favorably to published analyses accounting for known prognostic indicators.
Phase I: Ovarian and Prostate Cancers
Design:	Up to 20 patients receiving EGFRvIII peptide immunotherapy with either KLH or GM-CSF.
Status:	No significant toxicities noted to date. Immune responses to EGFRvIII observed in 2 of 4 evaluable patients.
Completed:
Phase I: Malignant Glioma
Design:	Single arm study utilizing ex vivo dendritic cells pulsed with CDX-110; single center (Duke).
Status:	16 patients completed treatment (13 with GBM). Therapy was well tolerated, and most patients developed EGFRvIII specific T cell responses. Median survival ~20 months, and two of two patients with measurable disease had long-term tumor regression after therapy.
Data presented at World Federation of Neuro-Oncology II/European Association for Neuro-Oncology VI (WFNO-II/EANO-VI) May 5–8, 2005, Edinburgh, United Kingdom
Planned:
Phase II: Ovarian Cancer
Design:	Randomized, multi-center study.
Status:	Planned for 2007.