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Background: Treatment options for patients with advanced esophageal or esophagogastric junction (EGJ) cancer are limited. Current guidelines for first-line treatment of advanced esophageal or EGJ cancer recommend chemotherapy containing a platinum and a fluoropyrimidine agent. Pembrolizumab demonstrated antitumor activity in previously treated patients with advanced esophageal cancer and in patients with gastroesophageal junction cancer. Aim: To describe the design and rationale for the randomized, double-blind, placebo-controlled Phase III KEYNOTE-590 study, which will be conducted to investigate pembrolizumab in combination with chemotherapy as first-line treatment in patients with advanced esophageal or EGJ cancer.Clinical trial registry & ID: ClinicalTrials.gov: NCT03189719.

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is an employee of MSKCC and MSKCC has an institutional collaboration agreement with IBM for Watson for Oncology and receives royalties from IBM, is the Chair of the Board of Directors of the Mesothelioma Applied Research Foundation, reports receiving commercial research grants from MedImmune, Epizyme, Polaris, Sellas Life Sciences, BMS, and Millenium, and is a consultant/advisory board member for Epizyme and Aldeyra Therapeutics. J.F. Vansteenkiste reports receiving research funding/honoraria from MSD, AZ, BMS, BI, and Roche and is a consultant/advisory board member for AZ, BMS, BI, MSD, and Roche. K. Baker-Neblett, X. Wang, L. Yan, I. Mitrica, and M.P. DeYoung are employees of and hold ownership interest in GlaxoSmithKline. J. Vasquez is an employee of GlaxoSmithKline. D.I. Bellovin is an employee of and holds ownership interest in Five Prime Therapeutics. J.H.M. Schellens is an employee of and holds ownership interest in Modra Pharmaceuticals and is a consultant/advisory board member for Debiopharm. J.M. Trigo reports receiving speakers' bureau honoraria from BMS and BI and is a consultant/advisory board member for BMS, BI, Merck, and Takeda. No potential conflicts of interest were disclosed by the other authors. Ethical approvalAll procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

5541 Background: Quisinostat is an orally bioavailable potent pan-histone deacetylase inhibitor. Combinations of HDAC inhibitors with paclitaxel or cisplatin demonstrate promising results in preclinical models with cisplatin and paclitaxel resistant OC. In phase Ib study the dosage of Quisinostat in combination of paclitaxel and carboplatin recommended for the phase II study was 12 mg. We report results of the phase II study of Quisinostat in combination with paclitaxel and carboplatin in pts with recurrent platinum resistantOC. Methods: the main inclusion criteria was tumor progression observed not less than 1 month and no more than 6 months after completion of the planned number of cycles of 1st line platinum/paclitaxel based CT. Quisinostat was administered at dose 12 mg p.o. each 3 week cycle on Days 1, 3, 5, 7, 9, 11 with of paclitaxel (175 mg/m2) and carboplatin (AUC5) on Day 7 of each cycle, for 2ndline. Pts received up to 6 cycles. The primary efficacy endpoint is the objective response rate (ORR) verified by the ICR. The secondary endpoints include safety, progression free survival (PFS) and overall survival. The study design implies the use of the two-stage Simon model: 29 patients who underwent treatment would provide 80% power for hypothesis testing in order to frequency of the ORR 30% (α = 0.05). Results: 31 pts were enrolled (30 pts evaluated). Median age was 57 years. Twenty one pts (67.7%) received all 6 cycles of therapy. ORR was 50.0% (15 pts). Median duration of response was 5 months (4.2-5.7). Median PFS - 6 months (95%CI 4.4-7.6). Any SAE were seen in 16.1% pts, AE of grade 3 and 4 – in 71% and 48.4% pts temporarily discontinued therapy due to AE. Dose reduction of CT due to AE was performed in 22.6% pts. The most common adverse events were neutropenia – 67,7%, nausea – 61.3%, weakness – 29%, thrombocytopenia – 22.6%, neuropathy – 19.4%, vomiting – 19.4%. Conclusions: Quisinostat in combination with paclitaxel and carboplatin in pts with recurrent platinum resistant ovarian cancer showed high efficacy and good tolerability Clinical trial information: NCT02948075.