Mahipal Sinnollareddy, Kinjal Sanghavi, Leonid Gibiansky, Tommy Li, Matthew Putnins, Mohamed-Eslam F Mohamed, Poliana Patah, Elena Favaro, Manish Gupta, Apurvasena Parikh, Steven Xu
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引用次数: 0
Abstract
Background: Epcoritamab is approved for treating various relapsed/refractory (R/R) lymphomas. In a phase I/II study in R/R follicular lymphoma (FL) patients, epcoritamab demonstrated high response rates (EPCORE NHL-1: objective response rate [ORR]: 82.0%, complete response [CR] rate: 62.5% [N = 128]; EPCORE NHL-3: ORR: 95.2%, CR rate: 76.2% [N = 21]) with durable responses and a manageable safety profile with a 2-step step-up dosing (SUD) regimen (0.16/0.8/48 mg [full dose]; Cycles 1-3: once-weekly dosing [QW], Cycles 4-9: every 2-week dosing [Q2W], Cycles 10+: every 4-week dosing [Q4W]).
Methods: A prior population pharmacokinetic model was updated and exposure-response analyses performed to support the selected dosing regimen (0.76-48 mg full doses evaluated).
Results: Higher epcoritamab exposure was associated with higher efficacy (ORR, CR rate, progression-free survival, overall survival; p < 0.05) with potential response rate plateau at 48-mg exposures. Initial response occurred in 96.2% of responders during QW with most maintaining/improving response during Q2W and Q4W, independent of Cycle 4+ exposure. No meaningful trends between epcoritamab exposure and treatment-emergent adverse events were identified, including cytokine release syndrome (CRS). Further optimization using a 3-step SUD regimen (0.16/0.8/3/48 mg), with adequate hydration and dexamethasone prophylaxis in Cycle 1, lowered CRS frequency and severity compared with the 2-step SUD regimen. Similar pharmacokinetics and B-cell depletion occurred with 3-step and 2-step SUD regimens. Median IL-6 levels remained consistently low after each Cycle-1 dose and beyond with the 3-step but not 2-step SUD regimen.
Conclusion: These analyses support and confirm the recommended 3-step SUD regimen with 48 mg full epcoritamab dose administered QW-Q2W-Q4W in patients with R/R FL.
期刊介绍：
Clinical Pharmacokinetics promotes the continuing development of clinical pharmacokinetics and pharmacodynamics for the improvement of drug therapy, and for furthering postgraduate education in clinical pharmacology and therapeutics.
Pharmacokinetics, the study of drug disposition in the body, is an integral part of drug development and rational use. Knowledge and application of pharmacokinetic principles leads to accelerated drug development, cost effective drug use and a reduced frequency of adverse effects and drug interactions.
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