3500 Background: Our preclinical model established the rationale for using azacitidine to reverse platinum resistance. Sequential azacitidine and carboplatin treatment conferred an effect against platinum resistant ovarian cancer cells that was greater than from each agent alone (synergistic interaction). Based on a well tolerated phase I regimen of azacitidine 75 mg/m2/day for 5 days plus carboplatin AUC 5 on day 2 once every 28 days, we initiated a phase IIa trial to evaluate efficacy. Methods: Patients with pathologically confirmed epithelial ovarian cancer who progressed within 6 months after a platinum-based regimen (resistant, Plat-RS, n=18) or on a platinum- based regimen (refractory, Plat-RF, n=12), were eligible to receive sequential azacitidine and carboplatin. All patients had measurable disease. Results: Thirty patients received a total of 159 cycles of treatment and 2 patients are still being actively treated at the cycle 14 and 19, respectively. Side effects include neutropenia, anemia, fatigue, nausea, and pain/irritation at the injection sites. All patients were followed for more than 12 months or until death. Remarkably, our regimen resulted in 1 CR, 3 PR (RR: 14%) and 10 SD in 29 evaluable patients, which is in stark contrast to no responses to a carboplatin-based regimen in a similar cohort of patients in the same institution. The median duration of response was 7.5 months. OS at 1-yr was 53%. Patients classified as having Plat-RS disease had an objective response of 22% and one-year OS of 67% compared to 0% and 33% in Plat-RF patients, respectively. Conclusions: To the best of our knowledge, this is the first phase II trial in epithelial ovarian cancer patients that demonstrates the ability of a hypomethylating agent to reverse platinum resistance. Based on these data, a randomized phase III trial in patients with platinum-resistant epithelial ovarian cancer is warranted. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pharmion, Inc Pharmion, Inc. Pharmion, Inc