Glenmark presents new pharmacokinetic data for immuno-oncology drug candidate

Glenmark Pharmaceuticals presented new pharmacokinetic data from its ongoing Phase 1 trial of GBR 1302, a HER2xCD3 bispecific antibody, at the European Society for Medical Oncology Immuno-Oncology (ESMO-IO) Congress 2018 in Geneva, Switzerland. GBR 1302 is Glenmark’s lead immunooncology candidate and is currently in a first-in-human trial to determine maximum tolerated dose (MTD) in an all-comers population of patients with a variety of HER2 positive cancers. The Phase 1 data will inform dosing regimen optimization of GBR 1302.

“Due to the anticipated potency and limited clinical experience with T-cell redirecting bispecific antibodies, determining the optimal dosing regimen for innovative investigational medicines like GBR 1302 is key to unlocking its potential,” said Dr. Mahboob Rahman, President and Chief Medical Officer at Glenmark Pharmaceuticals. “An innovative method of quantification was developed to facilitate the measurement of very low systemic concentrations of GBR 1302 in the clinical study. These findings provide insights into the pharmacokinetics of GBR 1302 and inform dosing regimen decisions to maximize its potential effectiveness for patients with HER2 positive cancers.”

A low starting dose of 1 ng/kg was selected for the first-in-human Phase 1 study of GBR 1302, and dose escalation continued in small increments using a biweekly regimen. Glenmark developed and utilized a novel hybrid immunocapture-LC/MS/MS method for quantification of GBR 1302 in human serum to overcome the difficulty of generating pharmacokinetic data at the low doses administered in the study.

Pharmacokinetic profiles of GBR 1302 were observed from doses of 30 ng/kg and beyond. In general, maximum concentration (Cmax) was observed close to the end of infusion, after which serum concentrations declined bi-exponentially, with a mean terminal half-life of approximately four to seven days. Both, Cmax and exposure, showed near dose-proportional increases up to 750 ng/kg, the highest dose evaluated in the Phase 1 trial thus far.

Consistent with the half-life findings, Glenmark plans to initiate a study of GBR 1302 in HER2 positive breast cancer patients with a weekly dosing regimen.