Population pharmacokinetics and exposure-safety relationship of nanoliposomal irinotecan (MM-398, nal-IRI) in patients with solid tumors.

e13588 Background: MM-398 is a nanoliposomal irinotecan (nal-IRI). This study characterized the population PK and exposure–response with MM-398 in patients with solid tumors. Methods: Population PK analysis was performed for total irinotecan (IRI) and its active metabolite SN-38 in 353 patients administered MM-398 60-120 mg/m2 in 6 studies. Covariates include body size (BSA), hepatic and renal functions (UGT1A1*28 7/7, bilirubin, liver metastasis, AST, ALT, albumin, CrCl), demographics (sex, race, age), and external factors (co-treatment with 5-FU, manufacturing site). Exposure-safety (neutropenia, diarrhea, and anemia) relationships were evaluated from 6 studies. Predictions of incidence rates of AEs were obtained from exposure-safety and predicted exposure with a dose of 80mg/m2. Results: Population PK of IRI was described as a 2-compartmental model, and SN-38 as a 1-compartmental model. Significant covariates to IRI were race and BSA; covariates to SN-38 were baseline bilirubin and BSA. No other covari...