Researchers affiliated with the ACTIVATE and ACT II trials have reported that the investigative vaccine CDX-110 has demonstrated impressive survival results when compared with historical controls for patients with glioblastoma multiforme (GBM). These results were recently presented at the 2008 annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois.

Glioblastoma multiforme is the most common primary brain malignancy, affecting approximately 10,000 individuals annually in the United States. Standard therapy for GBM includes resection, radiation therapy, and chemotherapy. Several novel therapeutic agents, namely targeted agents and immune-stimulating vaccines, are currently being evaluated for treatment of GBM, several of which appear to be at least as effective as standard therapies alone.

The epidermal growth factor receptor vIII (EGFRvIII) is a functional variant of the EGFR, a validated target for the treatment of various cancers. The EGFRvIII variant was originally discovered in GBM, and is a transforming oncogene that is not present in normal tissues. Besides GBM, EGFRvIII has been found in breast, ovarian, prostate, colorectal, and head and neck cancers. The investigational vaccine CDX-110 targets EGFRvIII.

The ACTIVATE trial was a Phase II trial that included 21 patients with newly-diagnosed GBM that expressed EGFRvIII. Patients had undergone gross-total resection followed by conformal radiation therapy and concurrent Temodar® ([temozolomide], 75 mg/m2 per day) with no progression of disease.¹ Sixteen patients went on to receive three doses of CDX-110 mixed with granulocyte-macrophage colony stimulating factor (GM-CSF) (142 mcg) intradermally at two week intervals, and five patients received saline placebo for three vaccinations in a blinded fashion. All patients then received monthly CDX-110 plus GM-CSF until disease progression. Evaluation of safety included adverse events, physical and neurological exams and laboratory studies.

• Median survival time was 26 months (95% CI: 21.6, infinity).
• Median time-to-progression (TTP) was 14.2 months.
• Median survival in a historical matched cohort was 15.2 months (95% CI: 13.9, 20.5) (p=0.0001).
• Median TTP in the historical matched control was 7.13 months (p=0.0001).
• There were no significant adverse events reported.

The ACT II study included 23 patients with a treatment schema and safety assessment similar to ACTIVATE.² The early saline placebo phase used in the ACTIVATE study was omitted, and two doses of maintenance Temodar were evaluated (13 patients received 200 mg/m2 daily times five every 28 days, while 10 received 100 mg/m2 daily times 21 days every 28 days for a maximum of 12 cycles). Monthly CDX-110 vaccination mixed with GM-CSF was given on day 21 of each cycle until tumor progression.

• Median overall survival has not yet been reached, but is estimated to be 33.1 months, based on preliminary results.
• The survival of a matched historical control group was 14.3 months (95% CI: 13.0, 16.2) and 15.2 months for a subgroup treated with Temodar (95% CI: 13.9, 20.5 p=0.0078).
• Time to progression was 16.6 months for patients in the ACT II study compared with 6.4 months for the historical control group (95% CI: 5.0, 14.1).
• Local injection site reaction was the primary reported toxicity.

Comments: Researchers associated with these two studies stated that it appears as if CDX-110 significantly improves survival in GBM with little toxicity. A Phase 2b/3 clinical trial referred to as ACTIII is currently enrolling patients at over 20 centers across North America; initiation of the Phase III trial is pending results from the phase 2b portion of the trial.

Related News:

Vaccination and Chemotherapy Appear to Work Together to Increase Survival in Patients with Glioblastoma (9/8/2004)

Clinical Course of Newly Diagnosed Glioblastoma Described (4/23/2008)

Radioactive Monoclonal Antibody Therapy Shows Promise in Glioblastoma Multiforme and Astrocytoma (3/3/2008)

Temodar®, CeeNU® and Radiation Therapy Promising for Glioblastoma (9/25/2006)

Reference: 

¹ Sampson, J, et al. Effect of EGFRvIII-Targeted Vaccine (CDX-110) on Immune Response and TTP when Given with Simultaneous Standard and Continuous Temozolomide in Paitents with GBM. Proceedings from the 2008 annual meeting of the Society of Clinical Oncology (ASCO) Abstract #2011.

² Pfizer. Updated CDX-110 Data in Glioblastoma Multiforme Presented at 44th Annual ASCO Annual Meeting. Available at: http://www.pfizer.com/news/press_releases/pfizer_press_releases.jsp?rssUrl=http://mediaroom.pfizer.com/portal/site/pfizer/index.jsp?ndmViewId=news_view&ndmConfigId=1010794&newsId=20080602006044&newsLang=en.