Clinical activity of the selective DRD2 antagonist ONC201, an imipridone, in metastatic endometrial cancer (mEC).

Abstract

5592 Background: mEC is a generally incurable, with limited therapeutic options. ONC201 is the founding member of the new class of compounds called imipridones that are orally active small molecules. ONC201 a specific antagonist of the G protein-coupled receptor DRD2 exerts antitumor activity via a series of established signaling pathways (dual inhibition ERK/AKT, integrated stress response). DRD2 expression is elevated in malignant versus normal endometrial tissue. Furthermore ONC201 has shown anti-cancer activity in preclinical models of EC. Methods: In a Phase I trial that included an expansion cohort, a total of 28 evaluable patients (pts) were treated with ONC201 at doses from 125mg every 3 weeks to 625 weekly. Five of these patients had advanced mEC. Results: The median age for the mEC patients was 60 years (56-72), the median number of prior treatments was 5 (3-6), 3 patients had prior radiation and all patients had prior surgery. One patient received 375mg ONC201 while the other 4 patients received 625mg ONC201, orally every 3 weeks. The median number of doses was 3 (2-14). Two of 5 patients exhibited regressions in individual metastatic lesions, however they did not qualify as overall objective responses by RECIST criteria. One of these two patients experienced stable disease for 42 weeks. There were no reported SAEs and no Grade > 1 AEs attributed to study drug. Conclusions: ONC201 is clinically active and well tolerated with oral administration in refractory mEC patients. Clinical trial information: NCT02250781. [Table: see text]