The study involves human epidermal growth factor receptor 2 (HER2)-expressing patients with either node-positive or high-risk node-negative breast cancer. Patients are randomized to receive AE37 plus granulocyte-macrophage colony-stimulating factor (GM-CSF) or GM-CSF alone (control). The primary endpoint is a reduction in cancer relapse after two years.
Generex Biotechnology Corp. (Toronto, Canada) reported that positive interim-phase 2 clinical data from its ongoing study of a novel Ii-Key hybrid-based HER-2/neu peptide vaccine (AE37) in HER-2 expressing breast cancer patients were presented at the 34th annual CTRC-AACR San Antonio Breast Cancer Symposium (SABCS) in San Antonio, TX, USA, in December 2011. The AE37 vaccine is being developed by its wholly-owned subsidiary, Antigen Express, Inc. (Worcester, MA, USA).
“We are encouraged by the positive interim results in disease-free survival demonstrated in the randomized phase 2 study with AE37 vaccine, especially in patients with low HER2 expression that are not currently eligible for Herceptin [trastuzumab, developed by Roche-Genentech (South San Francisco, CA, USA)],” said Dr. Eric von Hofe, PhD, president of Antigen Express. “While the number of patients with recurrent breast cancer is still too low to demonstrate statistical significance in this ongoing study, we project a sufficient number of events in 2012 and expect to report final results during this period.”
The results were presented at SABC by Col. George E. Peoples, MD, director, Cancer Vaccine Development Program, on December 7, 2011. “Women with breast cancers expressing low levels of HER2 do not benefit from targeted HER2 therapies that are currently available,” said Col. Peoples, a leading researcher in adjuvant breast cancer-vaccine development. “Our research is focused on reducing the recurrence of cancer using a woman’s own immune system to fight her disease, including breast cancers that express low levels of HER2. The AE37 vaccine is based on over five years of research and continues to show potential in a well-designed and ongoing randomized phase 2 clinical trial that if positive, will allow rapid transition to phase 3.”
There are currently over 250 patients enrolled in the phase 2 study. Kaplan-Meier projections of updated data presented at SABCS demonstrate that disease-free survival in the low HER2 expressing patients was 88.6% in the treated group (n = 53) versus 71.9% in the control arm (n = 78) at a median follow-up of 22 months. Patients treated with vaccine also showed a statistically significant increase in positive immune reactions to a test dose of HER2 (AE36 [HER2:776-790]) protein including maintenance of positive immune response up to 12 months postvaccination while there have been no changes in immune responses for control patients.
The company is assessing the data for potential opportunity to move forward with a phase 3 clinical development program following an end-of-phase 2 meeting with the US Food and Drug Administration (FDA) for AE37, which Antigen Express believes, if validated, could occur in the first half of 2012.
Antigen Ii-Key hybrid technology platform entails the modification of fragments of antigens to increase their potency in stimulating critical members of the immune response, known as CD4+ T helper cells. Integrating the Ii-Key modification along with tumor-associated antigens can significantly enhance the immune system’s capability to recognize and destroy cancer cells bearing any of the targeted antigens as well as increasing immunologic memory.
The first product candidate utilizing the company’s Ii-Key Hybrid technology platform is a HER-2/neu peptide vaccine (AE37). This “off-the-shelf” cancer immunotherapy candidate is easier and less expensive to produce than comparable cell-based approaches. AE37 is derived from a peptide fragment of the human epidermal growth factor receptor 2 (HER2) oncoprotein, which is expressed in a range of tumors including 75-80% of breast cancers as well as a high percentage of prostate, ovarian, and other cancers. AE37 represents the only HER2-based peptide vaccine currently being evaluated in a randomized trial and its use is not restricted to patients with a specific type of human leukocyte antigen (HLA) peptide.
For women whose cancer tests positive for increased quantities of the HER2, approved targeted therapies include trastuzumab (Herceptin; manufactured by Roche-Genentech, South Francisco, CA, USA). However, only 25% of breast cancer patients have HER2 levels high enough to be eligible for Herceptin. AE37 is positioned initially as an adjuvant therapy for at least 50% of breast cancer patients; i.e., those with low-to-intermediate levels of HER2 expression.
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Generex Biotechnology
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