Abstract CT119: Early results from a phase II study of RRx-001, a novel, triple epigenetic inhibitor, showing resensitization to irinotecan in colorectal cancer

Abstract

Abstract Background: Resistance acquisition to standard therapy in advanced colon cancer leads to poor patient survival. Epigenetic therapies can potentially reverse the chemoresistant phenotype. RRx-001, a novel ROS-mediated epigenetic modifier may resensitize to irinotecan-based therapies and increase overall survival compared to standard third-line regorafenib. Methods: The phase II ROCKET study evaluates a sequential rechallenge to irinotecan-based therapies after RRx-001 or regorafenib. Patients with an ECOG PS 0-1 with irinotecan-refractory metastatic colorectal cancer who progressed on oxaliplatin-, and irinotecan-based regimens with or without bevacizumab, cetuximab or panitumumab are randomized 2:1 to receive RRx-001 16.5 mg/m2 IV 1x/week or regorafenib 160 mg orally 21 of 28 days until progression or unacceptable toxicity followed by treatment with refractory irinotecan-based therapies. The primary end point is overall survival with secondary endpoints to investigate resensitization. The study is planned to accrue approx. 190 patients and recruitment is ongoing. Study Status and Results: To date, 23 patients have been randomized with 10 patients evaluable for resensitization. Post RRx-001 patients demonstrated marked decreases in CEA in all 6 patients as compared to 4 patients receiving regorafenib who were too systemically unwell to proceed to subsequent treatment. Conclusions: Early results in this study suggest that resensitization to irinotecan-based therapies mediated by RRx-001, a systemically non-toxic novel epigenetic inhibitor, may be a general effect. These early results are intriguing and may predict for 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 R. Fanger, Scott Caroen, Christopher Parker, Jan Scicinski. Early results from a phase II study of RRx-001, a novel, triple epigenetic inhibitor, showing resensitization to irinotecan in colorectal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT119. doi:10.1158/1538-7445.AM2015-CT119