Impact of food and high gastric pH on the bioavailability of the WEE1 inhibitor Debio 0123 assessed in a phase 1 dose escalation study

Presented at AACR Annual Meeting 2024

Anne Bellon¹,Omar Saavedra², Ingrid M. E. Desar³, Mathilde Jalving⁴, Jourik A. Gietema⁴, Carla Van Herpen³, Stefan Van Ravensteijn³, Esteban Rodrigo Imedio¹, Sylvia Van Haren¹, Melanie Wirth¹, Sandrine Micallef¹, Vito Dozio¹, Rikke Frederiksen Franzen¹, Marie-Claude Roubaudi-Fraschini¹, Valerie Nicolas-Metral¹, Hans Gelderblom⁵.

1 Debiopharm International S.A., Lausanne, Switzerland
2 Vall d’Hebron University Hospital, Barcelona, Spain
3 Radboud University Medical Center, Nijmegen, Netherlands
4 University Medical Center Groningen (UMCG), Groningen, Netherlands
5 Leiden University Medical Center, Leiden, Netherlands

Background

Debio 0123, an oral brain-penetrant, highly selective WEE1 inhibitor, is currently in clinical development, both as monotherapy and in combination, for the treatment of patients with solid tumors. Food and gastric acid-reducing agents e.g. proton pump inhibitors (PPIs) may modify the solubility, bioavailability, safety and efficacy of oral cancer drugs. Polymedication in cancer patients is common and food restrictions can impact patient compliance and wellbeing. In order to adequately inform drug dosing in clinical trials, effects of food and high gastric pH on Debio 0123 bioavailability were studied over three cycles in patients participating in arm B of a dose escalation Phase 1 study in combination with carboplatin (CTID NCT03968653).