FDA Accepts sBLA for Glofitamab Plus Chemotherapy in Relapsed/Refractory DLBCL
核心洞察
The FDA has accepted Roche's sBLA for glofitamab combined with gemcitabine and oxaliplatin (GemOx) for relapsed/refractory DLBCL (搜索) patients ineligible for autologous stem cell transplant.
The sBLA is based on the phase 3 STARGLO trial, which demonstrated a statistically significant and clinically meaningful improvement in overall survival compared to rituximab plus GemOx.
The FDA is expected to make a decision on the approval of glofitamab in combination with GemOx by July 20, 2025, offering a potential new treatment option.
The FDA has accepted Roche's supplemental Biologics License Application (sBLA) for glofitamab-gxbm (Columvi) in combination with gemcitabine and oxaliplatin (GemOx) for the treatment of patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL (搜索)) who have received at least one prior line of therapy and are not candidates for autologous stem cell transplant. The FDA is expected to decide on approval by July 20, 2025.
The sBLA is based on data from the phase 3 STARGLO trial (NCT04408638), which demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) with the glofitamab and GemOx combination compared to rituximab (Rituxan) and GemOx. The safety profile of the combination was consistent with the known safety profiles of the individual agents.
STARGLO Trial Results
The STARGLO trial is a phase 3, multicenter, open-label, randomized study evaluating the efficacy and safety of glofitamab in combination with GemOx versus rituximab in combination with GemOx in patients with R/R DLBCL (搜索) who have received at least one prior line of therapy and are not candidates for autologous stem cell transplant, or who have received two or more prior lines of therapy. The primary endpoint of the trial was OS, and secondary endpoints included progression-free survival (PFS), complete response rate, overall response rate, duration of response (DOR), and safety and tolerability.
In the primary analysis, conducted after a median follow-up of 11.3 months, patients treated with glofitamab plus GemOx showed a significantly longer length of survival, with a 41% reduction in the risk of death (HR, 0.59; 95% CI, 0.40-0.89, P =.011) compared with the rituximab and GemOx regimen. The median OS was not reached (95% CI, 13.8-NE) with the glofitamab regimen compared with 9 months (95% CI, 7.3-14.4) with the rituximab and GemOx regimen.
At a median follow-up of 9.6 months, the median PFS with glofitamab was 12.1 months (95% CI, 6.8-18.3) versus 3.3 months (95% CI, 2.5-5.6) with rituximab (HR, 0.37; 95% CI, 0.25-0.55; P < .000001).
Safety Profile
Safety data showed that adverse event (AE) rates were higher with the combination of glofitamab and GemOx versus rituximab and GemOx. Cytokine release syndrome (CRS) was one of the most commonly seen AEs and was generally low grade. Any grade CRS was noted in 44.2% of patients, with grade 1, 2, and 3 CRS seen in 31.4%, 10.5%, and 2.3% of patients, respectively. Further, CRS primarily occurred in cycle 1.
Expert Commentary
“For people with aggressive lymphomas like DLBCL (搜索), timely intervention with effective therapies can be crucial to reduce the risk of disease progression and improve long-term outcomes,” said Levi Garraway, MD, PhD, Roche’s chief medical officer and head of global product development. “We are encouraged by the overall survival benefit seen with this Columvi combination and hope it can become an important treatment option for those who are in need of alternative therapies.”
About Glofitamab
Glofitamab is an off-the-shelf, fixed-duration treatment that engages and redirects T cells to eradicate malignant B cells. When given as a monotherapy, glofitamab has produced deep and durable complete remissions in patients with relapsed/refractory DLBCL (搜索) following two or more prior lines of treatment. In June 2023, the FDA granted accelerated approval to glofitamab for use in this population.