A molecular signature index technology that can lead to better radiation therapy decisions for patients with cancer is being developed into a reliable radiosensitivity test by CvergenX, Inc., an advanced cancer diagnostics company. It is being done in conjunction with the National Cancer Institute’s Clinical Assay Development Program (CADP).
Research collaborations between CvergenX and Moffitt Cancer Center have preliminary data on the molecular signature’s efficacy in trials for patients with rectal, esophageal, head and neck cancers and, most recently, for patients with breast cancer. The NCI has selected the technology, called InterveneXRT ™, for further development and validation in a commercial collaboration agreement with CvergenX with the aim of making an assay that is ready for use in clinical trials and approval by the U.S. Food and Drug Administration.
To date, the technology has been developed and correlated with retrospective clinical outcomes over more than seven years of research and with the help of more than $2 million in funding primarily from the NCI.
“Developing a radiosensitivity predictive assay has been a goal of radiation biology for decades,” said Javier F. Torres-Roca, M.D., a member of the Radiation Oncology, Chemical Biology and Molecular Medicine Programs at Moffitt and co-founder and chief scientific officer of CvergenX. “This effort supports the emphasis on personalized medicine, where the goal is to use molecular signatures to guide therapeutic decisions.”
According to Torres-Roca, approximately 60 percent of all cancer patients receive radiotherapy during their treatment. Until now, no molecular diagnostic or biomarker for radiosensitivity had been developed to predict its benefit. Once the assay is fully developed, Intervene XRT ™ may reduce the need for radiation therapy when the assay shows which patients will or will not respond to treatment.
The radiosensitivity molecular signature was originally developed based on gene expression for 10 specific genes and a linear regression algorithm. It was developed in 48 cancer cell lines using a systems-biology strategy focused on identifying biomarkers for cellular radiosensitivity.
The initial effort is focused on rectal cancer where preoperative radiotherapy is part of the standard of care for patients with stage 2 or 3 disease. However approximately 40 percent of patients do not experience a clinical response to pre-operative treatment. The CADP goal is to show whether this assay will “identify patients who will not benefit from preoperative chemoradiation (with 90 percent negative predictive value), enabling physicians to make informed decisions about the use of chemoradiation for these patients.”
The work will be done by the Clinical Assay Development Network, a nationwide network of CLIA certified labs (labs conforming to the Clinical Laboratory Improvements Amendments, 1988) who have placed a bid with the NCI to carry out the project. The NCI will provide the financing, expertise and labor for the assay development.
According to Mary Del Brady, chairman and CEO of CvergenX, the individualization of radiation therapy is an important component of personalized cancer treatment.
“We are the first commercial enterprise to develop a companion diagnostic to radiation therapy, joining a growing group of personalized medicine companies that are applying genomics-based analysis to clinical practice,” said Brady. “Our goal is to have a validated test with proven clinical utility in the marketplace within the next three years. The test will provide more information, and far greater accuracy, than oncologists have ever had, enabling them to adjust their clinical management for better outcomes for their patients.”