Englumafusp alfa (CD19–4-1BBL costimulator) + glofitamab (CD20×CD3) drives 56.6% CMR in R/R aggressive B‑NHL

Englumafusp alfa is an off-the-shelf CD19-targeting 4-1BBL co-stimulatory fusion protein designed to augment T-cell activation, combined here with glofitamab, a CD20×CD3 T-cell–engaging bispecific antibody, with obinutuzumab given 7 days before first glofitamab and glofitamab step-up dosing in cycle 1. In this open-label, nonrandomized Phase 1 dose-escalation study (NCT04077723; CTIS 2022-502616-37-00), 134 patients with R/R B‑NHL were enrolled (aggressive n=109; indolent n=25); in the aggressive B‑NHL C2D8 subgroup (n=83) ORR was 68.7% with complete metabolic response (CMR) 56.6%, and in CAR-T–naïve aggressive patients (n=41) ORR/CMR were 73.2%/65.9%—numerically in the ballpark of CD19 CAR‑T outcomes reported across pivotal LBCL programs (typically ORR ~58–82%, CR ~39–58%), but achieved with an “off-the-shelf” bispecific-based backbone rather than individualized cell therapy. Safety was consistent with a high-intensity immune-engaging regimen: AEs in 98.5%, grade 3/4 AEs in 59.0%, and grade 5 AEs in 10 patients; MTD was not reached, with one DLT (grade 5 Pneumocystis jirovecii pneumonia).