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Background <p>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% [<i>N</i>&#xa0;=&#xa0;128]; EPCORE NHL-3: ORR: 95.2%, CR rate: 76.2% [N&#xa0;=&#xa0;21]) with durable responses and a manageable safety profile with a 2-step step-up dosing (SUD) regimen (0.16/0.8/48&#xa0;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]).</p> Methods <p>A prior population pharmacokinetic model was updated and exposure–response analyses performed to support the selected dosing regimen (0.76–48&#xa0;mg full doses evaluated).</p> Results <p>Higher epcoritamab exposure was associated with higher efficacy (ORR, CR rate, progression-free survival, overall survival; <i>p&#xa0;</i>&lt;&#xa0;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&#xa0;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.</p> Conclusion <p>These analyses support and confirm the recommended 3-step SUD regimen with 48&#xa0;mg full epcoritamab dose administered QW-Q2W-Q4W in patients with R/R FL.</p> Clinical Trial Registration <p>ClinicalTrials.gov: NCT03625037, NCT04542824</p>

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Exposure–Response Analyses to Inform the Optimal Epcoritamab Monotherapy Dosing Regimen in Relapsed or Refractory Follicular Lymphoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月1日

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  • Mahipal Sinnollareddy,
  • Kinjal Sanghavi,
  • Leonid Gibiansky,
  • Tommy Li,
  • Matthew Putnins,
  • Mohamed-Eslam F. Mohamed,
  • Poliana Patah,
  • Elena Favaro,
  • Manish Gupta,
  • Apurvasena Parikh,
  • Steven Xu

摘要

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.

Clinical Trial Registration

ClinicalTrials.gov: NCT03625037, NCT04542824