9P Preliminary population pharmacokinetic (popPK) co-variates and exposure response (ER) assessment of QT for RP-3500, a highly potent and specific inhibitor of ataxia telangiectasia and Rad3-related (ATR) protein kinase

摘要: BackgroundRP-3500 is an oral inhibitor of ATR (ATRi) in development for the treatment of patients (pts) with advanced solid tumors carrying alterations in ATRi-sensitizing genes. We report popPK co-variates and effect on QT prolongation in 120 pts treated with RP-3500 in the phase 1 TRESR study (NCT04497116).MethodsPK samples were collected from 120 pts on multiple days across doses and schedules during the dose-finding portion of the study. Pt demographics and baseline characteristics were collected at study enrollment. Triplicate electrocardiograms (ECGs) were collected prior to any drug administration and in conjunction with PK sampling at time points up to 4 hr post-RP-3500 dose. A popPK model was developed using Phoenix WinNonLin. PK co-variates were analyzed to assess the effect of age, sex, body weight (BW), body surface area (BSA), and renal/hepatic function on RP-3500 PK …