A Randomized, Placebo-Controlled Phase Ii Trial Comparing Gemcitabine Monotherapy To Gemcitabine In Combination With Azd 1775 (Mk 1775) In Women With Recurrent, Platinum-Resistant Epithelial Ovarian, Primary Peritoneal, Or Fallopian Tube Cancers: Trial Of Princess Margaret, Mayo, Chicago, And California Consortia.

TPS5613 Background: Platinum resistant ovarian cancer (OC) remains a therapeutic challenge. The majority of high grade serous OC (HGSOC) harbor TP53 mutations leading to increased dependency on S- and G2-phase checkpoints. Wee1 inhibition with AZD 1775 (MK 1775) induces G2 checkpoint escape. Gemcitabine is an antimetabolite therapy that kills cells undergoing DNA synthesis and blocks the progression of cells through the G1/S phase boundary. Preclinical data have shown that the addition of AZD 1775 to gemcitabine increased activity in platinum resistant OC cell lines and xenograft models. We propose to evaluate the combination of gemcitabine/AZD 1775 in patients (pts) with platinum resistant OC. Methods: A multicenter 2:1 randomized phase 2 trial was designed to evaluate the progression free survival (PFS) of subjects with recurrent platinum-resistant/refractory OC receiving gemcitabine in combination with AZD 1775 compared to subjects receiving gemcitabine in combination with placebo (NCT02151292). Eligib...