Abstract B26: RRx-001, a novel epigenetic modulator: Resensitization to previously failed therapy in the ongoing phase 2 colorectal cancer study, ROCKET

Abstract

Abstract Background: The development of resistance to chemotherapies in cancer leads to disease progression resulting in impaired survival. Resensitization to these previously effective but now failed therapies could lead to improvements in patient survival and response. RRx-001, a novel dinitroazetidine ROS-mediated epigenetic modulator that has demonstrated activity against DNMTs and HDACs may resensitize colorectal cancer patients to previously effective irinotecan therapies resulting in improvements in survival. Methods: The ROCKET study is a two stage trial that investigates RRx-001-mediated resensitization to irinotecan therapies. Patients with metastatic colorectal cancer who previously responded, then progressed on irinotecan-based therapies, with or without bevacizumab, cetuximab or panitumumab and an ECOG PS 0-1 are randomized in Stage 1 to receive RRx-001 1xweek or regorafenib until progression or unacceptable toxicity. Patients then advance to Stage 2 to receive irinotecan-based therapies. Target accrual is approx. 190 patients and the primary endpoint is overall survival with secondary endpoints to investigate resensitization. Recruitment is ongoing. Study Status and Results: To date, 28 patients have been randomized with 20 entering the resensitization stage of the study. 13 post RRx-001 patients entered the second stage of the study showing an improving patient survival, marked decreases in CEA and radiological responses. In contrast, the 7 regorafenib patients eligible for stage 2 were too systemically unwell to proceed to subsequent treatment. Conclusions: Early results suggest that RRx-001, a systemically non-toxic epigenetic agent, may resensitize colorectal cancer patients to irinotecan-based therapies. These interesting early results appear to be generalized and may translate to increased overall survival, adding an additional regimen after disease progression. The trial is continuing. Citation Format: Tony Reid, George Fisher, Corey Carter, Cheryl Cho-Phan, Pamela Kunz, Bryan Oronsky, Gary Fanger, Meaghan Stirn, Scott Caroen, Christopher Parker, Jan Scicinski. RRx-001, a novel epigenetic modulator: Resensitization to previously failed therapy in the ongoing phase 2 colorectal cancer study, ROCKET. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Sep 24-27, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2016;76(2 Suppl):Abstract nr B26.