Epigenetic Resensitization to Platinum in Recurrent, Platinum-Resistant Ovarian Cancer (OC) Using Guadecitabine (SGI-110), a Novel Hypomethylating Agent (HMA): Results of a Randomized Phase II Study.

5547Background: Development of resistance to platinum (P) is fatal in OC and epigenetic changes are linked to this process; a previous phase II study demonstrated efficacy of decitabine and carboplatin (C) in P-resistant OC. A phase I trial established the safety of guadecitabine (G), a 2nd-generation, subcutaneously (SC) administered HMA in combination with C. Here we present clinical results of a randomized study comparing G+C to treatment choice (TC) chemotherapy. Methods: This was an open-label, randomized, controlled study in which subjects with recurrent P-resistant high grade serous OC, no limits on prior therapy, measurable (RECIST or CA125) disease, ECOG 0-1, and normal organ function were randomized 1:1 to receive 28-day cycles of G+C vs. TC (pegylated liposomal doxorubicin, topotecan, paclitaxel or gemcitabine). Tumor assessments were performed every 8 weeks. TC pts could crossover to G+C at progression. The primary endpoint was PFS; secondary endpoints were RECIST and CA-125 response rate, 6-m...