Population Pharmacokinetic (poppk) Model of Pembrolizumab (pembro; MK-3475) in Patients (pts) Treated in KEYNOTE-001 and KEYNOTE-002.

3058 Background: The anti–PD-1 antibody pembro has efficacy in advanced cancer pts. We characterized pembro PK properties and quantified the effect of clinical factors on exposure. Immunogenicity was also assessed. Methods: Pooled popPK analysis was performed to characterize pembro serum concentrations over time in pts with melanoma (n = 1077), non-small cell lung cancer (n = 46), and other advanced cancers (n = 16) treated in KEYNOTE-001 and KEYNOTE-002. Simulations were performed to evaluate the magnitude of the effects of several clinical covariates on exposure. To investigate the immunogenicity potential of pembro, the development of antidrug antibodies (ADA) was determined. Results: A 2-compartment model with linear clearance from the central compartment adequately describes the clinical pharmacokinetics of pembro over the 1-10 mg/kg dose range (Table). No significant differences in efficacy have been observed for pembro 2 and 10 mg/kg Q3W and 10 mg/kg Q2W and Q3W. The PK profile is similar to other monoclonal antibodies, with a low clearance (0.2 L/day), limited central volume of distribution (3.8 L), and low to moderate variability (22-41%). The effect of age, sex, geographic location, baseline ECOG PS, eGFR, AST, bilirubin, albumin, glucocorticoid coadministration, tumor type and burden, and prior ipilimumab on pembro exposure is limited, as alterations of 20% or less are predicted by the popPK model. Of 268 pts evaluable for ADA, 1 (<1%) developed confirmed treatment-emergent ADA with no impact on efficacy or safety. Conclusions: The pembro PK profile indicated a low clearance and limited volume of distribution, consistent with other monoclonal antibodies. There was no clinically meaningful effect of baseline clinical factors on pembro exposure. Pembro has limited potential to elicit the formation of ADA. Clinical trial information: NCT01295827 and NCT01704287.Median (90% prediction interval) PK parameters of pembro at steady state based on popPK model. PK Parameter Pembro Dose Regimen 2 mg/kg Q3W 10 mg/kg Q3W 10 mg/kg Q2W Cmax (μg/mL) 64.6 (43.9; 99.2) 318 (215; 488) 393 (261; 691) Ctrough (μg/mL) 22.3 (8.84; 50.1) 110 (40.8; 257) 185 (82; 395) AUCss, 6 wk (μg∙day/mL) 1398 (713; 2730) 6859(3403; 13712) 10353 (5308; 20137)