Coleman RL, Handley KF, Burger R, et al. - Researchers examined the safety and preliminary efficacy of demcizumab (DLL4 targeted IgG2 humanized monoclonal antibody; potent inhibitor of the Notch pathway) in combination with weekly paclitaxel in platinum-resistant epithelial ovarian cancer (EOC). Further, they sought for the maximum tolerated dose or maximum administered dose. A 3 + 3 dose-escalation trial was performed including 19 patients with recurrent, platinum-resistant EOC with RECIST v. 1.1 measurable disease and ≤ 4 prior chemotherapy regimens. They targeted two dosing cohorts (2.5 mg/kg and 5 mg/kg); however, an evaluation of an intermediate dose level (3.5 mg/kg) was planned if the 5 mg/kg dose was not tolerable. Administration of demcizumab was done on days 1 and 15 and paclitaxel was provided weekly on days 1, 8, and 15 for each of three 28-day cycles: repetition of the 3-cycle doublet was done once if safe. Thereafter, the administration of paclitaxel was performed until unacceptable toxicity or disease progression. They identified no dose-limiting toxicities; however, they enrolled the intermediate dose level (3.5 mg/kg) and expanded it based on emerging safety data from other trials in the demcizumab program. Outcomes revealed that with a manageable toxicity profile, demcizumab in combination with paclitaxel showed activity in patients with heavily pretreated platinum-resistant ovarian cancer.