Scientific Poster Session IV - Original Research

Original Research
  Tuesday, November 14, 2023
  08:30 AM–10:00 AM

Abstract

Introduction: ONC201 (dordaviprone) is a novel, orally administered, anti-cancer imipridone with demonstrated antitumor effects in patients with glioma. ONC201 is eliminated primarily by the hepatic enzyme cytochrome P450 3A4

Research Question or Hypothesis: What is the effect of moderate hepatic impairment (HI) on ONC201 pharmacokinetics (PK)?

Study Design: Open-label, parallel, single-period, single-dose

Methods: Eight participants with moderate HI as assessed by Child-Pugh criteria, and 8 participants matched for age (±10 years), body mass index (±20%), and sex, with normal hepatic function, received a single 125mg dose of ONC201. PK blood samples were collected from predose to 168 hours postdose and analyzed for ONC201 using a validated liquid chromatography tandem mass spectrometry method. PK and safety profiles were evaluated between cohorts.

To assess the effect of HI on ONC201 exposure, point estimates and 90% confidence intervals (CIs) were calculated for the ratio of geometric means for PK parameters between cohorts.

Results: All 16 participants were included in the analysis population. Geometric mean ratios and 90% CIs of ONC201 exposure in the HI cohort compared to the healthy-matched cohort were 1.21 (0.88 to 1.67), 1.49 (1.02 to 2.20), and 1.54 (1.04 to 2.28), respectively, for Cmax, AUClast, and AUCinf. Two treatment-emergent adverse events (TEAEs), COVID-19 and atrial fibrillation, were reported in 2 healthy-matched participants; both events were mild and considered not related to ONC201. No participants in the HI cohort reported TEAEs.

Conclusion: The ratio of ONC201 exposure between cohorts was less than 2-fold higher in the HI cohort compared to the healthy-matched cohort. Single dose 125mg ONC201 was well tolerated in both cohorts. The results of this study will be used to inform dosing in patients with HI.

Presenting Author

Odin Naderer PharmD
Chimerix, Inc.

Authors

Margaret Anderson BS
Chimerix, Inc.

Thangam Arumugham Ph.D.
Chimerix

Angela Bartkus MBA, BSN RN
Chimerix, Inc

Joelle Batonga MSc
Certara

Marion Morrison MD
Chimerix

Mark Mullin BS
Chimerix, Inc.

Shamia Faison PhD, PMP
Certara

Tim Tippin PhD
Chimerix, Inc.