CLINICAL PHARMACOKINETICS OF ADAVOSERTIB IN THE PRESENCE OR ABSENCE OF PD-L1 INHIBITOR DURVALUMAB IN PATIENTS WITH REFRACTORY SOLID TUMORS.

Background: Adavosertib (AZD1775; AD), a highly selective WEE1 inhibitor, is mainly metabolized by CYP3A4 and FMO3. AD is a time-dependent inhibitor of CYP3A4 and weak reversible inhibitor of CYP2C8, − 2C9 and − 2C19. Toxicity in the initial cohort of AD and durvalumab (DB; PD-L1 inhibitor) in a Phase I study (NCT02617277) led to hypothesis that immune-mediated increase in cytokine levels and consequent suppression of CYP expression may alter AD exposure. We evaluated the impact of DB on AD pharmacokinetics (PK); safety and tolerability data were presented at ASCO 2019.