Figure 5. Proposed model for PK/PD-guided administration of ONC201 as a combinatorial anti-cancer agent.

ONC201 is particularly attractive for combinatorial regimens due to a short half-life and PD that persists for days to weeks. Due to this unique PK/PD relationship, ONC201 could be administered one to two days prior to another anti-cancer agent that would allow for a synergistic PD overlap (green lines) while avoiding drug-drug interactions.