Our lung cancer program involves combining entinostat as an immunomodulatory agent with antibodies targeting programmed cell death protein 1 (PD1) or programmed cell death ligand 1 (PDL1). Data from a completed Phase 2 NSCLC clinical trial with entinostat combined with azacitidine suggest that entinostat may prime tumors to be more responsive to subsequent immune therapy targeting PD1 or its ligand, PDL1. Further, preclinical studies have indicated that entinostat works to enhance the activity of immune therapy by inhibiting the activity of host immune cells that function to suppress the activity of anti-tumor immune responses.
- ENCORE 601: Phase 1b Clinical Trial. Phase 1b Clinical Trial. Based on these findings and emerging preclinical data demonstrating synergistic combined anti-tumor effects of entinostat and immune therapy, we are currently planning a Phase 1b clinical trial to examine the combination of entinostat with antibodies targeting PD1 to characterize the safety, define a recommended Phase 2 dose and assess the preliminary clinical activity of this combination. The trial will combine entinostat with Merck’s KEYTRUDA® (pembrolizumab), the first anti-PD-1 therapy approved in the United States, in patients with either advanced non-small cell lung cancer (NSCLC) or melanoma. We anticipate initiating this trial in the second half of 2015 with safety, recommended Phase 2 dose, preliminary activity and correlative data available in mid-2016.
- J1353: Epigenetic Priming to Immunotherapy Trial. This investigator-sponsored Phase 2 clinical trial, funded by Stand Up To Cancer, is currently enrolling up to 120 patients with metastatic NSCLC and is designed to test the ability of epigenetic therapy of entinostat and azacitidine in combination to enhance the response of NSCLC patients to Bristol-Myers Squibb’s OPDIVO® (nivolumab), a type of immunotherapy. We expect to see the interim efficacy data for this trial in mid-2016.
In order to fully understand the potential for entinostat to potentiate the activity of immune therapies, we plan to work with our collaborators to initiate a series of additional clinical studies in combination with targeted immune therapies in melanoma, breast cancer, lung cancer or other solid tumors.