CHMP Recommends Approval of Glofitamab Plus Chemotherapy for R/R DLBCL

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended the approval of glofitamab (Columvi) in combination with gemcitabine and oxaliplatin for the treatment of adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified who are ineligible for autologous stem cell transplant (ASCT).1

This recommendation was based on findings from the phase 3 STARGLO trial (NCT04408638), which demonstrated that glofitamab plus gemcitabine and oxaliplatin reduced the risk of death by 41% compared with rituximab (Rituxan) plus gemcitabine and oxaliplatin (HR, 0.59; 95% CI, 0.40-0.89; P = .011). The median overall survival (OS) was not evaluable (NE; 95% CI, 13.8-NE) for glofitamab plus gemcitabine and oxaliplatin (n = 183) vs 9.0 months (95% CI, 7.3-14.4) for rituximab plus gemcitabine and oxaliplatin (n = 91).1,2

“For patients with DLBCL who relapse after initial therapy, urgent and effective treatment is required to regain disease control,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche, stated in a news release.1 “As the first bispecific antibody to show improved survival in DLBCL in a randomized phase 3 study, [glofitamab] could offer an additional treatment option that is immediately available for patients who relapse.”

STARGLO Trial Design

The randomized, multicenter, open-label STARGLO trial enrolled patients with relapsed or refractory DLBCL who had received at least one prior line of therapy and were ineligible for ASCT, or who had received 2 or more prior lines of therapy.

Patients were stratified by number of prior lines of therapy (1 vs ≥2) and geographic region (North America vs Europe vs the rest of the world).2

Patients were randomly assigned in a 1:1 ratio to receive either glofitamab plus gemcitabine and oxaliplatin, or rituximab plus gemcitabine and oxaliplatin. In both arms, gemcitabine and oxaliplatin were given at 1000 mg/2 and 100 mg/m2, respectively, for a total of 8 cycles.2 In the experimental arm, glofitamab was given in a step-up fashion up to 30 mg for 8 cycles, then continued as monotherapy through cycle 12. Rituximab was dosed at 375 mg/m2 for up to 8 cycles.

The primary end point of the study was OS, and key secondary end points included progression-free survival (PFS), complete response rate, objective response rate, duration of response, and safety/tolerability.

Further Efficacy and Safety Findings

After a median follow-up of 7.2 months (95% CI, 6.1-9.2), the median PFS was 12.1 months (95% CI, 6.8-18.3) for glofitamab plus gemcitabine and oxaliplatin vs 3.3 months (95% CI, 2.5-5.6) for rituximab plus gemcitabine and oxaliplatin (HR, 0.37; 95% CI, 0.25-0.55; P < .0001).2

The safety profile of glofitamab plus chemotherapy was generally manageable and consistent with the known profiles of the individual agents with no new safety signals observed.

Any-grade, all-cause adverse effects (AEs) occurred in a higher percentage of patients receiving glofitamab plus gemcitabine and oxaliplatin (100%) compared with those receiving rituximab plus gemcitabine and oxaliplatin (96%).1,2

Cytokine release syndrome (CRS) occurred in 44.2% of patients treated with glofitamab plus gemcitabine and oxaliplatin (grade 1, 31.4%; grade 2, 10.5%; grade 3, 2.3%).1 CRS events were predominantly low grade and occurred primarily in cycle 1.

References

1. CHMP recommends EU approval of Roche’s Columvi combination for people with relapsed or refractory diffuse large B-cell lymphoma. Roche. February 28, 2025. Accessed February 28, 2025. https://www.roche.com/media/releases/med-cor-2025-02-28
2. Abramson JS, Ku M, Hertzberg M, et al. Glofitamab plus gemcitabine and oxaliplatin (GemOx) versus rituximab-GemOx for relapsed or refractory diffuse large B-cell lymphoma (STARGLO): a global phase 3, randomised, open-label trial. Lancet. 2024;404(10466):1940-1954. doi:10.1016/S0140-6736(24)01774-4