Optimal Dosing Regimen for Epcoritamab, a Subcutaneous Bispecific Antibody, in Relapsed or Refractory Large B-Cell...

Epcoritamab is a CD3xCD20 bispecific antibody that activates T cells to kill CD20-expressing B cells. Epcoritamab is approved for the treatment of adults with different types of relapsed or refractory lymphoma in various geographies, including the United States, Europe, and Japan. Epcoritamab demonstrated an overall response rate of 63%, a complete response rate of 39%, and manageable safety with the approved dosing regimen (0.16-mg and 0.8-mg step-up doses and 48-mg full dose, with dosing every week in cycles 1-3, every 2 weeks in cycles 4-9, and every 4 weeks in cycles ≥ 10) in patients with relapsed or refractory large B-cell lymphoma from the phase 1/2 EPCORE® NHL-1 trial expansion through January 31, 2022. Exposure-efficacy analyses including the EPCORE NHL-1 and EPCORE NHL-3 trials revealed that higher exposure was associated with a higher overall response rate, complete response rate, progression-free survival, and overall survival. A potential plateau of efficacy was observed at 48 mg or above. The exposure-safety analyses of these trials did not identify any safety concerns with the approved dosing regimen. No associations were detected between exposure and safety endpoints. The step-up doses were clinically active and helped mitigate cytokine release syndrome risk at the subsequent full doses. Most initial responses (94%) were observed during the weekly dosing period, and most responders with large B-cell lymphoma maintained or improved their response during every 2 weeks and every 4 weeks dosing. Overall, these analyses support the approved single-agent epcoritamab 0.16/0.8/48-mg dosing regimen in relapsed or refractory large B-cell lymphoma.