University of Colorado-developed treatment effective in Phase 2 Trials in a biomarker-selected group of patients
A combination therapy for treating cancer discovered at the University of Colorado Cancer Center showed improved survival rates in patients with advanced non-small cell lung cancer (NSCLC), according to results presented today from a double-blind, placebo-controlled phase 2 trial run by Syndax Pharmaceuticals.
The phase 2 results show that the combination of entinostat (Syndax’s SNDX-275) and erlotinib was more effective in treating NSCLC in patients with elevated levels of the molecular cancer marker E-cadherin than using erlotinib alone. University of Colorado Cancer Center researchers, who are faculty at the University of Colorado School of Medicine, were the first to identify elevated E-cadherin as a targetable cancer marker, the first to develop the biomarker tumor testing process for elevated E-cadherin and the first to test the combined therapy.
About 40 percent of NSCLC patients have elevated E-cadherin levels, making this a significant advance towards highly personalized treatment for lung cancer patients. Entinostat controls expression of genes that can cause resistance to conventional cancer therapies like erlotinib.
“The outcome of patients with advanced lung cancer has been disappointing historically but the identification of new molecular features and new therapies directed at these molecular features has markedly improved outcome for some patients,” said Paul Bunn, MD, professor of medical oncology at the CU medical school and principal investigator of the University of Colorado Cancer Center’s Specialized Program of Research Excellence in Lung Cancer, funded by the National Cancer Institute.
“Unfortunately, some of the molecular changes are quite rare,” said Bunn. “A more common molecular change is the high expression of epithelial markers such as E-cadherin. HDAC inhibitors such as entinostat can increase the expression of epithelial markers and can delay the development of resistance to EGFR inhibitors such as erlotinib. In this study, the combination of erlotinib and the HDAC inhibitor entinostat lead to a small but not statistically significant improvement in survival in unselected patients but a large and statistically significant improvement in survival in patients with high expression of E-cadherin ( 9.4 months vs.5.4 months). While extremely promising, these results will need to be confirmed in a larger randomized phase III trial.”
“Using a biomarker to select patients based on the tumor biology can improve patient outcomes versus treating an unselected patient population,” said University of Colorado Cancer Center researcher Fred Hirsch, MD, PhD, professor of medical oncology at the CU medical school.
Data from the phase 2 trial, led by Robert Jotte, MD, PhD, of Denver’s Rocky Mountain Cancer Center, was presented at the ASTRO 2010 Chicago Multidisciplinary Symposium in Thoracic Oncology, co-sponsored by the American Society for Radiation Oncology, the American Society of Clinical Oncology, the International Association for the Study of Lung Cancer and The University of Chicago.
“The data presented suggest that NSCLC patients with elevated E-cadherin levels can do better when treated with entinostat and erlotinib,” said Joanna Horobin, MD, president and chief executive officer of Syndax, the company that holds worldwide rights to entinostat. Syndax holds rights to the CU intellectual property related to this type of combination therapy, which includes the use of E-cadherin to predict responsiveness to the therapy.
“Syndax has been a model commercial partner for the University, and we are both encouraged and excited by the Phase 2 results,” said David Poticha, senior licensing manager at the CU Technology Transfer Office.
For more information regarding the presentation please visit http://www.thoracicsymposium.org/.
About non-small cell lung cancer (NSCLC)
Non-small cell lung cancer, a disease in which malignant cells form in the tissues of the lungs, is the most common type of lung cancer. The three main types of non-small cell lung cancer are squamous cell carcinoma, large cell carcinoma, and adenocarcinoma. Each year, there are more than 200,000 cases of newly diagnosed advanced NSCLC. About 60 percent of patients present with advanced NSCLC, meaning it has spread beyond the lung, when they are seen by a doctor. The five-year survival rate is less than 10 percent for patients with advanced NSCLC.
About the University of Colorado Cancer Center
The University of Colorado Cancer Center is the Rocky Mountain region’s only National Cancer Institute-designated comprehensive cancer center. NCI has given only 40 cancer centers this designation, deeming membership as “the best of the best.” Headquartered on the University of Colorado Denver Anschutz Medical Campus, University of Colorado Cancer Center is a consortium of three state universities (Colorado State University, University of Colorado at Boulder and University of Colorado Denver) and five institutions (The Children’s Hospital, Denver Health, Denver VA Medical Center, National Jewish Health and University of Colorado Hospital). Together, our 440+ members are working to ease the cancer burden through cancer care, research, education and prevention and control. Learn more at www.uccc.info.
About the University of Colorado School of Medicine
Faculty at the University of Colorado’s School of Medicinework to advance science and improve care. These faculty members include physicians, educators and scientists at University of Colorado Hospital, The Children’s Hospital, Denver Health, National Jewish Health, and the Denver Veterans Affairs Medical Center. Degrees offered by the University of Colorado School of Medicine include doctor of medicine, doctor of physical therapy, and masters of physician assistant studies. The School is located on the University of Colorado’s Anschutz Medical Campus, one of four campuses in the University of Colorado system. For additional news and information, please visit the UC Denver newsroom online.
About Syndax Pharmaceuticals
Syndax Pharmaceuticals, Inc. is a Waltham, MA-based, oncology-focused pharmaceutical company. Syndax is building a portfolio of new oncology products to extend and improve the lives of patients by developing and commercializing novel cancer therapies in optimized, mechanistically driven combination regimens. Formed in 2005, the company’s intellectual property is based on work from scientific founder Ronald Evans, Ph.D., recipient of the 2004 Albert Lasker Prize for Basic Medical Research, a Member of the National Academy of Sciences, a professor at the Salk Institute for Biological Studies and a Howard Hughes Medical Institute Investigator. Syndax has worldwide rights to develop and commercialize entinostat and is backed by top-tier Venture Capital firms: Domain Associates, MPM Capital, Avalon, Pappas and Forward Ventures. For more information please visit www.syndax.com.