JOHNS HOPKINS UNIVERSITY: Epigenetic therapy to sensitize patients with advanced NSCLC to chemotherapy and immunotherapy targeting reversal of immune tolerance


Year of Grant: 2014

Location: United States


Advanced, treatment resistant, non-small cell lung cancer (NSCLC) is the leading cancer killer in the world with five-year survival of only 5%. For the adenocarcinoma form of NSCLC (LUAD), there exists targeted therapies for specific genetic alterations for only 20% of patients. These yield robust initial responses but resistant disease generally returns within 1 year.


For the remaining 80%, especially in advanced disease, there are little available treatments to offer especially after initial failure of chemotherapy or targeted therapies. Advanced, treatment resistant, squamous cell NSCLC (LUSC) is an even worse scenario with no FDA approaches available.


Previous studies performed by the team of researchers at John Hopkins University found that epigenetic therapy appears to sensitize patients to subsequent treatments including chemotherapy, and very excitingly, to immunotherapy, targeting reversal of immune tolerance.


The new trial, which is based on preliminary results in earlier trials, involves 65 heavily pre-treated patients with NSCLC in which very durable responses were seen with: a) the epigenetic therapy alone (~3% of the patients); b) subsequent chemotherapy in another (~ 20%); and c) a new form of subsequent immunotherapy in which 5 out of 5 patients received medical benefit,  with 2 having stable disease for 8 months and 3 having robust RECIST criteria responses for over 1.5 years to date.


If validated, the study could in a delimited time span, introduce new therapies to radically alter the management of cancers like NSCLC.