LAUSR

2586Background: ONC201 is an orally active, small molecule selective antagonist of the G protein-coupled receptor DRD2 that has established a new class of compounds referred to as imipridones. A first-in-human trial of ONC201 defined its recommended phase II dose (RP2D) as 625mg using once every three week administration that was very well tolerated at doses that yielded antitumor effects. ONC201 also showed stimulatory effects on immune cells in preclinical studies, including increased intratumoral NK cell infiltration in xenografts. Based on the exceptional safety profile of ONC201, weekly dosing has been evaluated. Methods: This open-label, 3+3 dose-escalation study used a starting dose of 375mg and escalated to 625mg using a weekly administration schedule. The primary endpoint was to determine the RP2D of ONC201 and secondary endpoints included PD, PK, toxicity, and anti-tumor efficacy. Based on signs of clinical activity and preclinical tumor type sensitivity studies of ONC201, the patient population...