NP30179

Background

Phase I/II expansion single-arm pivotal trial (NP30179). 154 patients with relapsed or refractory DLBCL (including HGBCL, PMBCL, FL3B, DLBCL-TFL) after ≥2 prior lines including anti-CD20 and anthracycline, or after CAR-T failure. Evaluated glofitamab, a CD20×CD3 bispecific T-cell engager with a novel 2:1 bivalent CD20-binding format, using step-up dosing to reduce CRS. Pivotal trial supporting FDA approval of glofitamab in June 2023.

Interventions and follow up

Regimen: Glofitamab IV with obinutuzumab 1000 mg pretreatment (day −7), then step-up dosing (2.5 mg → 10 mg → 30 mg) and fixed 30 mg q3w for up to 12 cycles
Primary endpoint: Complete response rate (CRR) per IRC at any time point
Median follow-up: 12.6 months

Results

CR rate (IRC): 39.4%
ORR: 51.6%
12-month DOR (responders): 77.6%
12-month OS: 50.0%

Adverse events

Immune-mediated toxicities: CRS any grade 63.3%, grade ≥3 3.9% (step-up dosing substantially reduced severe CRS); ICANS any grade 11.7%, grade ≥3 3.2%
Cytopenias (grade ≥3): neutropenia 44.8%, anemia 13.6%
Management/mortality: tocilizumab in 29.9%; no treatment-related deaths from CRS

Conclusions

Glofitamab with step-up dosing achieved a 39.4% CR rate in heavily pretreated R/R DLBCL, with durable responses (77.6% maintained at 12 months) and a manageable CRS profile. Fixed-duration treatment (12 cycles) distinguishes it from continuous-therapy bispecifics and may offer a practical advantage.

Key Limitations

Single-arm design without a comparator; cross-trial comparisons with CAR-T and other bispecifics are confounded by differing eligibility and prior-therapy mix. Roughly a third of patients had prior CAR-T, complicating generalizability across the broader R/R population. Median follow-up of 12.6 months limits assessment of long-term durability and late relapse. CRS remains common (any grade 63%), requiring step-up dosing, obinutuzumab pretreatment, and inpatient monitoring during initial cycles.

Clinical Context

FDA granted accelerated approval to glofitamab for R/R DLBCL after ≥2 prior lines in June 2023; EMA approval followed in 2023. Glofitamab is a fixed-duration, off-the-shelf CD20×CD3 bispecific, contrasting with continuous-treatment epcoritamab. Both bispecifics provide an option after CAR-T failure or for CAR-T-ineligible patients. Ongoing trials are evaluating glofitamab in combination (e.g., with gemcitabine-oxaliplatin) and in earlier lines.

References