Celldex Starts Phase II/III Trial Of Peptide Vaccine In Brain Cancer
Celldex Therapeutics Inc. began a Phase II/III trial of its peptide vaccine CDX-110 in patients with newly diagnosed glioblastoma multiforme.
Company officials are encouraged by earlier Phase II data on disease progression and survival, and on updated data from that study to be presented at the upcoming American Society of Clinical Oncology meeting. CDX-110 is an immunotherapy that targets epidermal growth factor receptor variant III, a functional variant of EGFR.
The Phase II/III randomized study will enroll patients whose tumors express that mutation. It will compare the vaccine plus the standard of care, temozolomide (Temodar, Schering-Plough Corp.), to temozolomide alone at more than 20 brain cancer centers in the U.S. and Canada.
The Phase II portion of the ATC III trial is designed to enroll 90 patients. If improved disease control is seen at six months, Celldex would move into the Phase III portion of the study, which would include up to 285 additional patients.
Ron Newbold, vice president of business development at Phillipsburg, N.J.-based Celldex, said data to be presented at the ASCO meeting show "why we are excited about doing the Phase II/III trial. Our hope is that we see statistically significant improvements in time to progression and overall survival for these patients," adding that the Phase III portion of the study would start in about a year if all goes according to plan.
Newbold cited estimates showing there are about 10,000 new cases of glioblastoma multiforme, an aggressive form of brain cancer, each year in the U.S. About 45 percent of them express the EGFRvIII variant, he said.
Initial data from 23 patients in the Phase IIa study, named ACT II, showed median time to disease progression was 12.8 months, comparing favorably with a matched historical cohort (7.1 months) and published reports on temozolomide chemotherapy (6.9 months). Median survival in that trial had not been reached at 18 months, comparing favorably to a matched historical cohort (13 months) and temozolomide therapy (14.6 months).
The extension of that nonrandomized study in about 20 more patients is ongoing.
Newbold told BioWorld Today that Celldex in October began to introduce CDX-110 to potential partners from big biotech and pharmaceutical companies. He said the intention is to find a partner due to the potential size of the market for the product, which also is in Phase I trials in ovarian and prostate cancers. The company is evaluating opportunities in other indications, since EGFRvIII has been observed in other cancers, including breast, colorectal and head and neck.
"We see it as being a substantial product, a substantial commercial opportunity," Newbold said. "We don't want to get ahead of ourselves building a sales and marketing organization. We are fortunate to be talking to a number of companies. They are interested in the target and see the potential commercial and therapeutic opportunities."
The company has several products behind CDX-110, including CDX-1307, the lead program from its APC, or antigen-presenting cells, platform, which links antibodies and antigens for targeted delivery. CDX-1307, which is in two Phase I trials in various solid tumor types, was Celldex's lead program when it was formed in 2003 as a wholly owned subsidiary of Medarex Inc., of Princeton, N.J.
Celldex registered to go public in 2004, but later withdrew that filing and formally spun out from Medarex in October 2005 when it acquired Lorantis Ltd., of Cambridge, UK, and Alteris Therapeutics Inc., of Philadelphia. The deals brought to Celldex CDX-110 and other programs and technologies, along with $30 million in cash. Medarex's stake in Celldex was reduced to 60 percent, with Lorantis gaining 34 percent and Alteris 6 percent.
A third candidate at Celldex is CDX-2101, a viral-like particle-based product being developed for hepatitis B virus infection. Celldex is seeking a partner for that program to begin clinical trials in Asia, which are expected to start late this year or early next year.
Most of the rest of its preclinical pipeline is based on the APC technology, and includes compounds targeting solid tumors, HIV and human papillomavirus. The company also has technology around the Notch signaling pathway.
The company's cash is expected to last at least until the early part of 2008, said Anthony Marucci, vice president and chief financial officer at Celldex. He added that Celldex is exploring various financing alternatives.