PII-147 - POPULATION PHARMACOKINETIC MODELING OF NGM438 IN PATIENTS WITH ADVANCED OR METASTATIC SOLID TUMORS.

L. Yan¹, S. Xie², S. Boesmans², L. Rivera¹, W. Li¹, A. Goodyear¹, L. Zheng¹, D. Abhyankar¹, V. Hanes¹, J. Sloan-Lancaster¹; ¹NGM Biopharmaceuticals, ²Amador Bioscience.

Background: Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) is a collagen-binding inhibitory receptor expressed on immune cells. NGM438 is a humanized IgG1 monoclonal antibody that specifically binds to LAIR1 and blocks LAIR1/collagen engagement. Population analysis was conducted to characterize the pharmacokinetic (PK) properties of NGM438 in patients with advanced or metastatic solid tumors.

Methods: PK data from 25 subjects in a Phase 1/1b study of NGM438 as a monotherapy or in combination with pembrolizumab were simultaneously modeled using a population approach. Since 9.5% of post first dose PK data were recorded as below the limit of quantitation (BLQ), model development was performed using both M1 (excluding BLQ observations) and M3 (likelihood of BLQ observations) methods. The predictive performances of both models were assessed by goodness-of-fit diagnostics and visual predictive check (VPC).

Results: Following intravenous infusions, NGM438 PK were adequately described by a two-compartment model with parallel first-order and receptor-mediated nonlinear elimination pathways. Posterior VPC assessments demonstrated that M3 method substantially outperformed M1 for the overall fitting to NGM438 PK data. With the M3 method, estimated systemic clearance of the first-order elimination pathway (CL), central (Vc) and peripheral volume of distribution (Vp) were 0.285 L/d, 3.43 L and 1.94 L, respectively. Both CL and Vc increased with body weight, typical for therapeutic monoclonal antibodies. Baseline albumin was identified as a significant covariate, where lower albumin level was associated with faster CL of NGM438.

Conclusion: PK of NGM438 was typical for therapeutic monoclonal antibodies. Besides body weight, only baseline albumin level was identified as a relevant PK covariate. Age, sex, race and baseline peripheral blood mononuclear cell counts had no impact on NGM438 PK.