O3.8Early Results: "ROCKET" a phase II Study of XXXX , a novel triple epigenetic inhibitor, Resensitization to @entity2600 in @entity14 .

@entity1 @entity901 @entity137 @entity2600 @entity5 @entity984 @entity8486 @entity876 @entity376 @entity14 @entity64008
BACKGROUND: @entity64008 is a novel broad-spectrum anticancer agent that triply inhibits DNA methyltransferases (DNA MTases), Histone Deacetylases (HDAC), and @entity376 Demethylases. In the first-in- @entity1 , Phase I trial, 5/5 @entity1 who progressed on @entity64008 treatment were resensitized to previously refractory @entity2600 therapy, hinting at a generalized resensitization effect. A randomized open-label multi-part, multi-center phase II trial of @entity64008 versus @entity8486 (ROCKET) is underway to explore the resensitization and/or 'episensitization' potential in @entity2600 refractory @entity5 and its impact on overall survival. METHODS: @entity1 with @entity2600 -refractory metastatic @entity14 with an ECOG PS 0-1 who progressed on @entity901 -, and @entity2600 -based regimens with or without bevacizumab, cetuximab or panitumumab are randomized 2:1 to receive @entity64008 16.5 mg/m(2) IV 1x/week or @entity8486 160 mg orally 21 of 28 days until progression or unacceptable @entity137 followed by treatment with refractory @entity2600 -based therapies. RESULTS: To date, 23 @entity1 have been randomized with 10 @entity1 evaluable for resensitization. Post @entity64008 @entity1 demonstrated marked decreases in CEA in all 6 @entity1 as compared to 4 @entity1 receiving @entity8486 who were too systemically unwell to proceed to subsequent treatment. Progression free survival (ongoing) for @entity64008 + @entity2600 is 5.9 months compared 0.92 months on @entity8486 + @entity2600 . Combined Disease Control Rate (SD + PR) for the combination of @entity64008 and reintroduction of @entity2600 based therapy is currently 100%, whereas no @entity1 to date randomized to the @entity8486 arm have been able to start @entity2600 based therapy secondary to decreasing performance status. CONCLUSIONS: Early results in the ROCKET study suggest that @entity64008 -mediated resensitization to previously refractory therapies may have a generalized effect, independent of @entity984 or @entity876 status. These early results are intriguing and may be a major advancement in epigenetic therapy. @entity64008 is a novel pan-epigenetic inhibitor that may potentially offer improved QOL and overall survival over currently approved therapy in the chemotherapy refractory @entity14 .
