Epcoritamab (CD3×CD20 bispecific) exposure–response supports 48mg QW→Q2W→Q4W with lower CRS via 3-step ramp

Epcoritamab is a subcutaneous CD3×CD20 T-cell–engaging bispecific antibody; these updated population PK and exposure–response analyses across R/R follicular lymphoma (EPCORE NHL-1: ORR 82.0%, CR 62.5% [N=128]; EPCORE NHL-3: ORR 95.2%, CR 76.2% [N=21]) linked higher exposure with higher ORR/CR, PFS, and OS (all p<0.05), with a suggested efficacy plateau around 48mg exposure. Most responses declared early (96.2% of responders during weekly dosing), and later-cycle exposure (Cycle 4+) didn’t appear to drive further response deepening/maintenance, supporting de-escalation to Q2W then Q4W after induction. Safety showed no meaningful exposure–TEAE relationship (including CRS), and a 3-step step-up (0.16/0.8/3/48mg) plus hydration + dexamethasone in Cycle 1 reduced CRS frequency/severity vs a 2-step ramp, with similar PK and B-cell depletion; IL-6 stayed consistently low with the 3-step approach (NCT03625037; NCT04542824). Versus common ≥3L R/R FL options like mosunetuzumab (CD20×CD3; ORR ~80%, CR ~60%, median PFS ~17.9mo) or zanubrutinib+obinutuzumab (BTKi+anti-CD20; ORR ~69% vs 46% with obinutuzumab alone), these response rates look competitive—but this abstract is about optimizing regimen (not a head-to-head efficacy claim).