3827 - Pharmacokinetic (PK) analysis of weight-based and fixed dose cemiplimab in patients (pts) with advanced malignancies

Background

Cemiplimab (cemiplimab-rwlc in the US), a human monoclonal anti–PD-1 antibody, has shown substantial antitumour activity in pts with advanced malignancies and is FDA-approved for pts with advanced (metastatic or locally advanced) cutaneous squamous cell carcinoma (CSCC). We sought to compare weight-based and fixed dosing regimens of cemiplimab in pts with advanced malignancies.

Methods

This PK analysis included 505 pts with advanced tumours, including 135 pts with advanced CSCC, from phase I and phase II studies of cemiplimab (NCT02383212 and NCT02760498, respectively). Pts received either weight-based doses of cemiplimab (1, 3, 10 mg/kg every 2 weeks [Q2W] and 3 mg/kg every 3 weeks [Q3W]) or a fixed dose regimen (200 mg Q2W). This analysis pooled data from 10,935 PK samples including 2,023 samples from pts with advanced CSCC, to predict the Q3W fixed dose regiment with equivalent cemiplimab exposure as the recommended Phase II dose (3 mg/kg Q2W) using a 2compartment population PK (PopPK) model incorporating covariates that improved goodness-of-fit statistics. The selected fixed dose regimen was confirmed by PK data of the regimen in pts with advanced CSCC from the phase II trial.

Results

In the phase I study, dose-proportional kinetics were observed over the 1 to 10 mg/kg Q2W dose range. The 350 mg Q3W fixed dose regimen was selected based on PopPK model simulations as it provided similar cemiplimab exposure to 3 mg/kg Q2W at steady state (ss) over a 6-week (6wk) treatment period (e.g. mean AUC_{6wk, ss} [coefficient of variation (CV)]: 3,800 [37.2%] and 3,710 [35.9%] mg*day/mL for 350 mg Q3W and 3 mg/kg Q2W, respectively). The observed exposures in patients with advanced CSCC in the phase II trial receiving 350 mg Q3W cemiplimab were comparable to the simulated exposures. In addition, the observed exposures at ss were similar between 3 mg/kg Q2W and 350 mg Q3W.

Conclusions

The results from PopPK simulations support the use of a 350 mg Q3W fixed dose regimen, with similar cemiplimab exposure to a weight-based 3 mg/kg Q2W regimen, in pts with advanced malignancies.

Clinical trial identification

NCT02383212 and NCT02760498.

Editorial acknowledgement

Bu Reinen of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc., and Sanofi.

Legal entity responsible for the study

Regeneron Pharmaceuticals, Inc., and Sanofi.

Funding

Regeneron Pharmaceuticals, Inc., and Sanofi.

Disclosure

M.R. Migden: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Regeneron Pharmaceuticals, Inc.; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Genentech; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Eli Lilly; Honoraria (self), Travel / Accommodation / Expenses: Sun Pharma. A. Paccaly: Shareholder / Stockholder / Stock options, Full / Part-time employment: Regeneron Pharmaceuticals, Inc. K.P. Papadopoulos: Research grant / Funding (institution): Regeneron Pharmaceuticals, Inc.; Research grant / Funding (institution): Merck; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Merck KGaA; Research grant / Funding (institution): Mabspace Biosciences. F. Yang: Shareholder / Stockholder / Stock options, Full / Part-time employment: Regeneron Pharmaceuticals, Inc. J.D. Davis: Shareholder / Stockholder / Stock options, Full / Part-time employment: Regeneron Pharmaceuticals, Inc. R. Rippley: Shareholder / Stockholder / Stock options, Full / Part-time employment: Regeneron Pharmaceuticals, Inc. I. Lowy: Shareholder / Stockholder / Stock options, Full / Part-time employment: Regeneron Pharmaceuticals, Inc. M.G. Fury: Shareholder / Stockholder / Stock options, Full / Part-time employment: Regeneron Pharmaceuticals, Inc. E. Stankevich: Shareholder / Stockholder / Stock options, Full / Part-time employment: Regeneron Pharmaceuticals, Inc. D. Rischin: Research grant / Funding (institution), Non-remunerated activity/ies: Regeneron Pharmaceuticals, Inc.; Research grant / Funding (institution), Non-remunerated activity/ies: GSK; Research grant / Funding (institution), Travel / Accommodation / Expenses, Non-remunerated activity/ies: Merck; Research grant / Funding (institution), Non-remunerated activity/ies: Bristol-Myers Squibb; Research grant / Funding (institution): Roche.