FDA Accepts sBLA for Glofitamab in R/R Diffuse Large B-Cell Lymphoma

Supporting data for the sBLA came from the multicenter, open-label, randomized phase 3 STARGLO study (NCT04408638), which evaluated glofitamab with gemcitabine and oxaliplatin compared with rituximab (Rituxan) with gemcitabine and oxaliplatin in patients with relapsed or refractory DLBCL.

A supplemental biologics license application (sBLA) has been accepted by the FDA for glofitamab (Columvi) in combination with gemcitabine and oxaliplatin for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplant and have received at least 1 prior line of therapy, according to a press release from the developer, Roche.¹

The FDA is anticipated to have their decision on approving this regimen by July 20, 2025. Data that support this decision are also being submitted to other health authorities, like the European Medicines Agency, for approval consideration.

As a monotherapy used to treat people with relapsed or refractory DLBCL, glofitamab was the first fixed-duration bispecific antibody to receive accelerated approval by the FDA, as well as conditional marketing authorization in the EU.

Supporting data for the sBLA came from the multicenter, open-label, randomized phase 3 STARGLO study (NCT04408638), which evaluated glofitamab with gemcitabine and oxaliplatin compared with rituximab (Rituxan) with gemcitabine and oxaliplatin in patients with relapsed or refractory DLBCL.

“For people with aggressive lymphomas like DLBCL, timely intervention with effective therapies can be crucial to reduce the risk of disease progression and improve long-term outcomes. We are encouraged by the overall survival [OS] benefit seen with this [glofitamab] combination and hope it can become an important treatment option for those who are in need of alternative therapies,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Roche, wrote in a press release.¹

The primary analysis, assessed after a median follow-up of 11.3 months, found that patients treated with glofitamab had a 41% decrease in the risk of death compared with rituximab (HR, 0.59; 95% CI, 0.40-0.89; P = .011). The median OS was not reached (NR) for the glofitamab group vs 9 months for the rituximab group. The glofitamab group also had a higher median number of cycles when compared with the rituximab group at 11 vs 4, respectively.

At the updated analysis, assessed after a median follow-up of 20.7 months, the median OS was 25.5 months in the glofitamab group (95% CI, 18.3-not evaluable) and 12.9 months (95% CI, 7.9-18.5) in the rituximab group (HR, 0.62; 95% CI, 0.43-0.88).²

The study’s primary end point was OS. Key secondary end points were progression-free survival (PFS), complete response rate, objective response rate, and duration of objective response.

Regarding safety, 180 patients (100%) in the glofitamab group and 84 patients (96%) in the rituximab group experienced at least 1 adverse event (AE); 98 patients (54%) and 15 patients (17%) experienced at least 1 serious AE; 140 patients (78%) and 36 patients (41%) had at least 1 AE of grade 3 or higher; and 48 patients (27%) and 11 patients (13%) discontinued treatment due to an AE.

A total of 19 patients died due to an AE, 15 (8%) of whom were in the glofitamab group and 4 (5%) in the rituximab group. Additionally, 5 patient (3%) deaths were related to glofitamab, and 1 patient (1%) death in the comparator arm was related to rituximab.

Patients were randomly assigned in a 2:1 ratio, stratified by number of previous therapies and relapsed/refractory status, in permuted blocks of 6, to either the glofitamab group or the rituximab group. Dosage for the glofitamab group was as follows: 1000 mg/m² of intravenous gemcitabine and 100 mg/m² of oxaliplatin plus glofitamab in step-up dosing to 30 mg; all for 8 cycles, with 4 additional cycles of glofitamab monotherapy. Dosage for the rituximab group was as follows: 1000 mg/m² of intravenous gemcitabine and 100 mg/m2 of oxaliplatin plus 375 mg/m² of rituximab; all for a total of 8 cycles.

Patient eligibility criteria included having histologically confirmed DLBCL, at least 1 prior line of therapy, confirmed availability of tumor tissue, an ECOG performance status from 0 to 2, adequate hematologic function, and adequate renal function.³

References

1. FDA accepts supplemental Biologics License Application for Roche’s Columvi combination for people with relapsed or refractory diffuse large B-cell lymphoma. News release. Roche. December 5, 2024. Accessed December 5, 2024. https://tinyurl.com/5edss86j
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
3. A phase III study evaluating glofitamab in combination with gemcitabine + oxaliplatin vs rituximab in combination with gemcitabine + oxaliplatin in participants with relapsed/​refractory diffuse large B-cell lymphoma. ClinicalTrials.gov. Updated October 16, 2024. Accessed December 5, 2024. https://tinyurl.com/ytzatcpu