RiboMed, Tocagen Collaborate
News Jul 07, 2016
RiboMed Biotechnologies, Inc. and Tocagen Inc. have announced a collaboration to analyze potential epigenetic prognostic and predictive markers, including the gene for the DNA repair enzyme O-6-Methylguanine-DNA Methyltransferase (MGMT), in Tocagen’s clinical trials evaluating the investigational treatment Toca 511 & Toca FC in patients with recurrent high grade gliomas (HGGs).
HGGs, including glioblastoma, are the most aggressive primary malignant brain tumors and are treated initially with surgery, radiation and chemotherapy, including temozolomide (TMZ, Temodar®). Response to TMZ treatment is variable and almost all tumors ultimately recur. Tumor sensitivity to TMZ correlates with the inactivation of MGMT and longer overall survival in patients with glioblastoma. Inactivation of MGMT is primarily caused by DNA methylation in the MGMT gene’s control region.
Given the prognostic and predictive value of MGMT methylation status, this test has become an informative tool in the management of glioblastoma. RiboMed has developed a new validated test, which improves the reliability and accuracy of MGMT testing. A full description and validation of this technology and comparison to other commonly used DNA methylation methods was recently published in Epigenomics (http://www.futuremedicine.com/doi/pdf/10.2217/epi-2016-0004).
“Accurate diagnostics information is critical to help inform treatment decisions and expectations for outcomes,” said David Piccioni, M.D., Ph.D., neuro-oncologist at UC San Diego’s Moores Cancer Center. “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”.
Favorable safety and promising survival data from Tocagen’s Phase 1, open-label, ascending dose, multicenter trial, that included analysis of epigenetic markers of tumors by RiboMed were published in the cover article of the June 2016 issue of Science Translational Medicine (http://stm.sciencemag.org/content/8/341/341ra75). Based on the positive results reported in this study, Tocagen is now conducting an international Phase 2/3 trial, Toca 5; more information can be found by searching www.clinicaltrials.gov using the clinical trial identifier NCT 02414165).
In collaboration with RiboMed, the assay will be utilized to analyze MGMT status in tumors resected during the trial and evaluate association with potential treatment activity. The collaborative research also includes evaluation of RiboMed’s GliomaSTRAT assay initially in tumor samples from earlier clinical trials. GliomaSTRAT is designed to stratify gliomas by both tumor aggressiveness and potential for drug activity. In addition to MGMT methylation, GliomaSTRAT includes a DNA methylation biomarker panel to determine the tumor’s CpG Island Methylator Phenotype (CIMP) and detection of the IDH1 R132H mutation known to cause CIMP.
These prognostic biomarkers identify two distinct tumor subtypes that show significant differences in overall survival, independent of initial tumor grade classification. The ability to reliably analyze HGGs for multiple DNA methylation biomarkers, particularly with minimal material from FFPE tumor samples, has only recently become possible through the development of RiboMed’s extremely sensitive detection method for measuring both DNA methylation and point mutations using its core technology, Abscription®.
Scientists have identified sodium glucose transporter 2 (SGLT2) as a mechanism that lung cancer cells can utilize to obtain glucose, which is key to their survival and promotes tumor growth. The finding provides evidence that SGLT2 may be a novel biomarker that scientists can use to help diagnose precancerous lung lesions and early-stage lung cancers.READ MORE