A brain tumor is the growth of abnormal cells in the tissues of the brain. Although many growths in the brain are called brain tumors, not all are cancerous; in this case, they are called “benign.” When a brain tumor is classified as “malignant,” it is brain cancer. Malignant tumors grow and spread aggressively, overpowering healthy cells by consuming their space, blood and nutrients. Glioblastoma multiforme, also called grade IV astrocytoma or glioblastoma (GB), is the most common and most aggressive malignant primary brain tumor. Celldex is currently conducting a Phase 3 study in newly diagnosed EGFRvIII (also known as EGFRv3) positive glioblastoma and a Phase 2 study in relapsed EGFRvIII positive glioblastoma.

Glioblastoma Symptoms

Glioblastoma can develop in any area of the brain. Common symptoms of glioblastoma include seizure, nausea and vomiting, headache, and hemiparesis (defined as weakness on one side of the body). Memory, personality or other neurological problems may develop. The tumor can start producing symptoms quickly, or it can grow to a large size before it becomes symptomatic, depending in part on where it is located.

Glioblastoma Diagnosis & Treatments

Glioblastoma is usually diagnosed by a neurologist who will review medical history and perform a thorough exam, which includes checking vision, hearing, balance, coordination and reflexes. The doctor may also request imaging tests such as an MRI, CT, or PET scan of the brain. These tests show the location of the tumor and its effect on brain activity, function and blood flow. The first stage of treatment is usually surgery to attempt to remove as much of the tumor or tumors as possible. Surgery is typically followed by radiotherapy and chemotherapy. Temozolomide, a chemotherapy drug, is the current standard of care used to treat newly diagnosed glioblastoma.

Clinical Trials for Glioblastoma Multiforme

There are also investigational treatments for glioblastoma multiforme being evaluated in clinical trials. Some of these approaches are targeting mutations seen in glioblastoma. Our clinical development candidate, rindopepimut, is an investigational immunotherapy that targets the tumor specific oncogene (a gene that has the potential to cause or contribute to the growth of cancer) called EGFRvIII.

Targeting EGFRvIII in Glioblastoma Multiforme

EGFRvIII is expressed in tumors in about 30% of glioblastoma patients. EGFRvIII is a functional and permanently activated mutation of the epidermal growth factor receptor EGFR, a protein that contributes to cell growth and has been well validated as a target for cancer therapy. Unlike EGFR, EGFRvIII has not been detected at a significant level in normal tissues, but has been identified in glioblastoma; therefore, targeting of this tumor-specific molecule is not likely to impact healthy tissues. EGFRvIII can turn normal cells into malignant cells through its well documented oncogenic properties, providing a constant growth signal to tumor cells which express it. Consequently, cells producing EGFRvIII have an enhanced capacity for unregulated growth and are associated with more aggressive disease and worse prognosis.

EGFRvIII contains immunogenic characteristics, suggesting that immunotherapy might be used against this target. Immunotherapy is defined as treatment that uses certain parts of the immune system to fight diseases. Rindopepimut is an immunotherapy designed to activate the patient’s own immune system against tumor cells expressing the EGFRvIII mutation.

Learn more about rindopepimut.