A Sequential Population Pharmacokinetic Model of Zilovertamab Vedotin in Patients with Hematologic Malignancies Extrapolated to the Pediatric Population.

Background And Objectives: Recently a number of antibody-drug conjugate (ADC) pharmacometric models have been reported in the literature, describing one or two ADC-related analytes. The objective of this analysis was to build a population pharmacokinetic (popPK) three-analyte ADC model to describe efficacy and safety of zilovertamab vedotin, an ROR1-targeting ADC conjugated to monomethyl auristatin E (MMAE).

Methods: Data from a phase 1 study of zilovertamab vedotin in subjects with hematologic malignancies was used in a stepwise ADC modeling strategy based on the simplified ADC popPK model proposed by Gibiansky.

Forward and reverse translational approaches to predict efficacy of neutralizing respiratory syncytial virus (RSV) antibody prophylaxis.

Background: Neutralizing mAbs can prevent communicable viral diseases. MK-1654 is a respiratory syncytial virus (RSV) F glycoprotein neutralizing monoclonal antibody (mAb) under development to prevent RSV infection in infants. Development and validation of methods to predict efficacious doses of neutralizing antibodies across patient populations exposed to a time-varying force of infection (i.

V ACHER: Visualization of complex trial data in pharmacometric analyses with covariates.

Pharmacometric models can enhance clinical decision making, with covariates exposing potential contributions to variability of subpopulation characteristics, for example, demographics or disease status. Intuitive visualization of models with multiple covariates is needed because sparsity of data in visualizations trellised by covariate values can raise concerns about the credibility of the underlying model. V ACHER, introduced here, is a stepwise transformation of data that can be applied to a variety of static (non-ordinary-differential-equation-based) pharmacometric analyses.

Raltegravir (RAL) in Neonates: Dosing, Pharmacokinetics (PK), and Safety in HIV-1-Exposed Neonates at Risk of Infection (IMPAACT P1110).

Background: Adequate pharmacokinetic and safety data in neonates are lacking for most antiretroviral agents. Raltegravir is a selective HIV-1 integrase strand transfer inhibitor available in a granule formulation suitable for use in neonates and young infants as prophylaxis or treatment of HIV infection.

Methods: IMPAACT P1110 is a phase 1, multicenter, noncomparative dose-finding study of raltegravir in infants exposed to HIV-1 infection.