Accelerating drug development by efficiently using emerging PK/PD data from an adaptable entry-into-human trial: example of lumretuzumab

Cancer Chemotherapy and Pharmacology
Georgina Meneses-LorenteMartin Weisser

Abstract

This study aimed at evaluating if pharmacokinetic and pharmacodynamic data from the first few patients treated with an investigational monoclonal antibody in a dose-escalation study can be used to guide the early initiation of potentially more efficacious combination regimens. Emerging pharmacokinetic and pharmacodynamic data from the first nine patients treated with lumretuzumab (a glycoengineered anti-HER3 monoclonal antibody) monotherapy at doses from 100 to 400 mg q2w were used along with a pharmacokinetic model that incorporated target-mediated drug disposition to guide the selection of the starting dose for use in combination regimens. The dose-escalation study investigated lumretuzumab doses up to 2000 mg q2w and a maximum tolerated dose was not reached. However, the model described in this report predicted linear lumretuzumab pharmacokinetics and >95% target saturation at doses ≥400 mg q2w. These data, along with safety data, contributed to the decision to begin dose-escalation studies in combination with cetuximab and erlotinib using a starting dose of 400 mg lumretuzumab. Pharmacokinetic data from patients treated with lumretuzumab 400-2000 mg q2w in combination regimens were consistent with the model predictions. PK/...Continue Reading

References

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Feb 24, 2015·Cancer Chemotherapy and Pharmacology·Georgina Meneses-LorenteBirgit Bossenmaier
Oct 16, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Didier MeulendijksUlrik Lassen

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