Phase 1 multicenter trial of CUDC-907 in children and young adults with relapsed or refractory solid tumors, CNS tumors, and lymphoma.

10542Background: CUDC-907 is a first-in-class small molecule inhibitor of histone deacetylases and phosphatidylinositol-3-kinases. Data from pediatric preclinical models, and adult clinical studies suggest that CUDC-907 can downregulate Myc/Mycn, providing a potential therapeutic strategy for Myc/Mycn-driven pediatric tumors. Methods: Using a 3+3 dose escalation design, CUDC-907 was administered at 3 dose levels to patients 1-21 years of age with relapsed/refractory solid tumors, brain tumors and lymphomas (NCT02909777). Primary objectives were to determine the pediatric recommended phase II dose (RP2D), describe toxicities, and describe PK parameters. Other endpoints included antitumor activity and pharmacodynamic effects. Patients received CUDC-907 orally on a 5 days on / 2 days off (“5/2”) schedule in 28-day cycles, with a pediatric mini-tab formulation for children who could not swallow pills. Results: As of 11/16/2017, 15 patients enrolled, with a median age of 15 (4.6-20.9) years. Diagnoses included...