Background
Phase III, open-label RCT. 274 patients with R/R DLBCL (including high-grade BCL and DLBCL transformed from FL) after ≥1 prior line of anti-CD20 + anthracycline-containing therapy who were not eligible for ASCT. Glofitamab is a CD20×CD3 bispecific antibody (2:1 bivalent CD20 binding). STARGLO was the first Phase III RCT comparing a bispecific antibody combination versus standard chemotherapy in R/R DLBCL.
Interventions and follow up
Arm A: Glofitamab (step-up dosing 2.5mg → 10mg → 30mg fixed-duration 12 cycles) + gemcitabine 1000mg/m² + oxaliplatin 100mg/m² (GemOx) q21d × 8 cycles; obinutuzumab 1000mg pretreatment cycle 1 day 1 for CRS mitigation
Arm B: Rituximab 375mg/m² + gemcitabine 1000mg/m² + oxaliplatin 100mg/m² (R-GemOx) q21d × 8 cycles
Primary endpoint: Overall survival
Median follow-up: 21.3 months
Arm B: Rituximab 375mg/m² + gemcitabine 1000mg/m² + oxaliplatin 100mg/m² (R-GemOx) q21d × 8 cycles
Primary endpoint: Overall survival
Median follow-up: 21.3 months
Results
mOS: 25.5 vs 12.9 months, HR 0.59, 95% CI 0.40–0.89, P=.011
mPFS: 13.8 vs 3.6 months, HR 0.40, 95% CI 0.28–0.57, P<.001
ORR: 72.4% vs 51.7%
CR rate: 58.5% vs 31.7%
mPFS: 13.8 vs 3.6 months, HR 0.40, 95% CI 0.28–0.57, P<.001
ORR: 72.4% vs 51.7%
CR rate: 58.5% vs 31.7%
Adverse events
CRS/ICANS (glofitamab arm): CRS any grade 62.8%, grade ≥3 3.6%; ICANS any grade 6.6%, grade ≥3 2.2%; obinutuzumab pretreatment effectively mitigated CRS severity
Hematologic: Grade ≥3 neutropenia 57.1% vs 43.4%; thrombocytopenia 24.1% vs 34.3%
Infectious: Grade ≥3 infections 16.8% vs 11.7%
Hematologic: Grade ≥3 neutropenia 57.1% vs 43.4%; thrombocytopenia 24.1% vs 34.3%
Infectious: Grade ≥3 infections 16.8% vs 11.7%
Conclusions
Glofitamab + GemOx significantly improved OS (12.6-month gain, HR 0.59) and PFS versus R-GemOx in R/R DLBCL, representing a landmark Phase III OS benefit for a bispecific antibody-based regimen. STARGLO is the first randomized trial to demonstrate OS superiority of a bispecific-based regimen over standard chemotherapy.
Key Limitations
R-GemOx is an accepted but not universally preferred salvage regimen — some centers use R-DHAP or R-ICE. The obinutuzumab pretreatment added complexity and cost. Fixed-duration glofitamab (12 cycles) leaves open questions about optimal treatment duration. Post-progression outcomes and impact on CAR-T eligibility not fully characterized. Trial enrichment toward non-primary-refractory patients may favor prognosis; geographic enrolment imbalance noted.
Clinical Context
FDA approved glofitamab-gxbm (Columvi) in June 2023 for R/R DLBCL after ≥2 prior lines (accelerated approval based on single-arm GO29983 data); STARGLO OS data support broader use, and the glofitamab+GemOx combination received FDA approval in 2025. EMA has approved glofitamab. Glofitamab's fixed-duration regimen (unlike continuous epcoritamab) is a practical advantage. ESMO and ASCO guidance include bispecific antibodies for R/R DLBCL.