Rindopepimut with Temodar Appears Promising in Diagnosed Glioblastoma Multiforme

Cancer Connect

Maintenance therapy with rindopepimut (CDX-110) combined with Temodar® (temozolomide) resulted in a 70% progression-free rate at 5.5 months for newly diagnosed patients with glioblastoma multiforme (GBM). These findings were recently presented at the 2010 annual meeting of the American Society of Clinical Oncology (ASCO).[1]

GBM is one of the most common and fatal types of primary brain cancer. It develops from the glial cells, which are the most abundant cells in the nervous system. Glial cells provide supportive functions that facilitate the work of neurons (cells that transmit impulses between the brain, spinal column, and nerves). Current treatment for GBM includes surgery, followed by radiation and chemotherapy with Temodar. However, even with the most aggressive treatment available, many patients will survive less than one year after diagnosis. As such, researchers continue to evaluate new and innovative treatment strategies.

Rindopepimut is an investigational cancer vaccine that is designed to stimulate the immune system to attack targets found on cancer cells. This particular vaccine targets the epidermal growth factor receptor variant III, or EGFRvIII. It is estimated that 25-30% of GBM patients have EGFRvIII-positive disease.

In this Phase IIB study, newly diagnosed EGFRvIII-positive GBM patients were evaluated. Patients who had not experienced tumor progression following surgical removal, conformal radiation therapy, and Temodar were eligible to enroll in this study. Following successful initial treatment, patients continued treatment with Temodar in combination with rindopepimut. Interim results at 5.5 months of 40 out of the planned 65 patients indicate that 70% of patients had not experienced a progression of their disease. Rindopepimut was well tolerated with only one patient discontinuing treatment due to a hypersensitivity reaction.

These results are consistent with previous studies of rindopepimut in GBM. Ongoing studies may further elucidate the role of this promising investigational vaccine in the management of this difficult disease.

Reference:

[1] Lai R, Recht LD, Reardon DA, et al. Interim data for ACT III: Phase II trial of PF-04948568 (CDX-110) in combination with temozolomide (TMZ) in patients (pts) with glioblastoma (GBM). Presented at the 46th Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago, IL, June 4-8, 2010. Abstract 2014.

Comments (2)
No. 1-2
MedMaven
MedMaven

Editor

Any updates available on TOCA or some of the newer viral studies?

Endmathabusenow
Endmathabusenow

Unfortunately this is out-of-date. More recent studies showed no difference between Rindopepimut treatment and controls.

Lessons learned from rindopepimut treatment in patients with EGFRvIII-expressing glioblastoma
Lessons learned from rindopepimut treatment in patients with EGFRvIII-expressing glioblastoma

EGFRvIII is the most common mutation of EGFR and results in the creation of a tumor-specific antigen that is detectable in 23–33% of human glioblastoma (GBM) (1). EGFRvIII arises due to the deletion of EGFR exons 2–7, which generates a truncated extracellular domain capable of constitutive EGFR activation. The truncated extracellular domain creates a new peptide sequence, resulting in a unique, GBM cell-specific, antibody-reactive EGFRvIII antigen. This motivated the development of a peptide treatment strategy, known as rindopepimut (Rintega, formerly CDX-110) that consists of the EGFRvIII peptide conjugated to the adjuvant, keyhole limpet hemocyanin (KLH). The KLH adjuvant is utilized in a variety of cancer vaccine modalities for its strong immunogenicity and acceptable safety levels in humans after inoculation. In the ACTIV trial, rindopepimut was administered intradermally in conjunction with granulocyte-macrophage colony stimulating factor (GM-CSF) (2). Preclinical analysis of the EGFRvIII peptide treatment approach yielded substantial evidence of immune-mediated activity against intracerebral tumors, with a mechanism that included antibody-dependent cellular cytotoxicity (ADCC) (3). This sparked evaluation of rindopepimut in a series of clinical trials, including a phase II multi-center trial against EGFRvIII-expressing newly-diagnosed GBM whereby immunization occurred following gross total resection and standard of care adjuvant chemoradiotherapy. This trial reported an improved overall survival when compared to historical controls matched for entry criteria, prognostic factors, and TMZ treatment with best responses associated to a measurable serological EGFRvIII-specific antibody titer (4). Tumor progression was associated with a loss of EGFRvIII expression, suggesting at that time that rindopepimut induced a specific and effective immune response resulting in the successful eradication of GBM cells expressing the target antigen. It was then hypothesized that tumors escaped immunologic control following vaccination by losing the targeted EGFRvIII antigen. This study was followed by two additional phase II trials, ACT II (5) and ACT III (6) that, tested concurrent rindopepimut treatment with adjuvant TMZ, similarly demonstrating encouraging survival outcomes as compared to historical controls.


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