Abstract LB-268: Assessment of flat dosing strategy for INCMGA00012 in patients with advanced tumors

Abstract

Abstract Background: INCMGA00012, a humanized, hinge-stabilized, IgG4κ monoclonal antibody that recognizes human PD-1, is being developed for the treatment of multiple solid tumor types, both as monotherapy and in combination with other potentially immunoactive agents. Flat dosing is preferred to weight-based dosing for multiple reasons, including convenience of preparation and administration, reduced errors in preparation calculation, and minimization of drug waste. A modeling and simulation approach was employed to support flat doses for later phase studies. Patients and Methods: INCMGA00012 has been administered to approximately 200 participants in a Phase 1 study (Study INCMGA 0012-101) at weight-based doses ranging from 1 to 10 mg/kg Q2W or Q4W and at flat doses of 500 mg Q4W and 750 mg Q4W. PK data from weight-based doses were used for population PK model development and data from flat doses were used for model validation. Simulations were performed to support the selection of RP2 flat dose. Results: The concentrations of INCMGA00012 were adequately described by a 2-compartment model with first-order elimination. Higher clearance was estimated for 1 mg/kg (23.5 mL/h) than the other dose groups (13.5 mL/h). Body weight dependence of clearance and volume of distribution for central compartment were characterized by power relationships with exponents of 0.911 and 0.493, respectively. The model was validated using PK data from participants who received INCMGA00012 500 mg Q4W and 750 mg Q4W, respectively, in the cohort expansion phase. Median steady state trough concentrations of 500 mg Q4W and 750 mg Q4W exceeded the target value. Conclusion: Modeling and simulation provide justification for 500 mg Q4W for further clinical development of INCMGA00012 based upon favorable safety, PK characteristics and presumed flat exposure-response relationships for efficacy. Citation Format: Xuejun chen, Phil Wang, Sanjeev Kaul, Bradley Sumrow, Swamy Yeleswaram. Assessment of flat dosing strategy for INCMGA00012 in patients with advanced tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-268.