NEW YORK (GenomeWeb) – RiboMed Biotechnologies and Tocagen today announced a collaboration to use RiboMed's technology to analyze potential epigenetic prognostic and predictive markers in Tocagen's clinical trials evaluating the investigational treatment Toca 511 and Toca FC in patients with recurrent high grade gliomas (HGGs).
HGGs are the most aggressive primary malignant brain tumors. Currently, they are treated with surgery, radiation, and chemotherapy — including temozolomide. Clinicians have found that response to this treatment is variable and almost all tumors recur. Tumor sensitivity to temozolomide correlates with the inactivation O-6-methylguanine-DNA methyltransferase (MGMT), the gene for the DNA repair enzyme, and longer overall survival in patients with glioblastoma. Inactivation of MGMT is primarily caused by DNA methylation in the MGMT gene's control region.
RiboMed has developed a test that improves the reliability and accuracy of MGMT testing, and recently published validation results of this technology in Epigenomics. In Tocagen's Phase 1, open-label, ascending dose, multicenter trial, the researchers reported favorable safety and promising survival data for their investigational treatment in the June 1, 2016 issue of Science Translational Medicine.
Tocagen is now conducting an international Phase 2/3 trial, Toca 5. In its collaboration with RiboMed, Tocagen will use the new assay to analyze MGMT status in tumors resected during the trial and evaluate association with potential treatment activity.
The collaboration also involves evaluating RiboMed's GliomaSTRAT assay, a test designed to stratify gliomas by both tumor aggressiveness and potential for drug activity, initially in tumor samples from earlier clinical trials. In addition to MGMT methylation, the assay includes a DNA methylation biomarker panel to determine the tumor's CpG island methylator phenotype and detect the IDH1 R132H mutation. Both of these prognostic biomarkers identify distinct tumor subtypes that show significant differences in overall survival, independent of initial tumor grade classification.
"Accurate diagnostics information is critical to help inform treatment decisions and expectations for outcomes," David Piccioni, a neurologist at UC San Diego's Moores Cancer Center, said in a statement. "Having a test that can produce accurate and reliable MGMT promoter methylation data with minimal sample is an important advance for patients and their caregivers."