FDA to Review sBLA for Glofitamab Plus Chemotherapy in Relapsed/Refractory DLBCL

The FDA has accepted the supplemental biologics license application (sBLA) seeking the approval of glofitamab-gxbm (Columvi) for use in combination with gemcitabine and oxaliplatin (GemOx) for the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who have received at least 1 prior line of therapy and who are not candidates for autologous stem cell transplant (ASCT).1

The sBLA is based on data from the phase 3 STARGLO trial (NCT04408638), which demonstrated that the combination of glofitamab and GemOx led to a statistically significant and clinically meaningful improvement in overall survival (OS) vs rituximab (Rituxan) and GemOx. The safety profile of the investigational regimen was also comparable with the established safety profiles of the individual agents.

Findings from the STARGLO trial have also been filed to other health authorities around the world for potential approval, including the European Medicines Agency.

The FDA is expected to make a decision on the approval by July 20, 2025.

“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,” Levi Garraway, MD, PhD, Genentech’s chief medical officer and head of Global Product Development, said in a news release. “We are encouraged by the 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.”

In June 2023, the FDA granted accelerated approval to glofitamab for patients with relapsed/refractory DLBCL not otherwise specified or large B-cell lymphoma arising from follicular lymphoma, after 2 or more lines of systemic therapy based on findings from the phase 1/2 NP30179 trial (NCT03075696).2

STARGLO was designed as a confirmatory study intended to convert the accelerated approval to full approval. The multicenter, open-label, randomized study enrolled patients with relapsed/ refractory DLBCL following at least 1 prior line of therapy and who are not candidates for ASCT, or who have received at least 2 prior lines of therapy.1

The primary end point of the study was OS. Secondary end points included progression-free survival (PFS), complete response rate, objective response rate, duration of objective response, and safety and tolerability.3

Findings from the primary analysis, which had been conducted after a median follow-up of 11.3 months (95% CI, 9.6-12.7), demonstrated that the median OS was not reached (95% CI, 13.8 months-not evaluable [NE]) with the investigational regimen vs 9.0 months (95% CI, 7.3-14.4) with rituximab plus GemOx (HR, 0.59; 95% CI, 0.40-0.89; P = .011).1,3

After a median follow-up of 7.2 months (95% CI, 6.1-9.2) for PFS, the median PFS was 12.1 months (95% CI, 6.8-18.3) for glofitamab plus GemOx vs 3.3 months (95% CI, 2.5-5.6) for rituximab plus GemOx (HR, 0.37; 95% CI, 0.25-0.55; P < .0001).3

In the updated analysis, which was conducted after a median follow-up of 20.7 months (95% CI, 19.9-23.3), the median OS was 25.5 months (95% CI, 18.3-NE) with glofitamab plus GemOx vs 12.9 months (95% CI, 7.9-18.5) with rituximab plus GemOx (HR, 0.62; 95% CI, 0.43-0.88). After a median PFS follow-up of 15.7 months (95% CI, 13.4-17.0), the median PFS was 13.8 months (95% CI, 8.7-20.5) with glofitamab plus GemOx vs 3.6 months (95% CI, 2.5-7.1) with rituximab plus GemOx (HR, 0.40; 95% CI, 0.28-0.57).

Regarding safety, the rates of adverse effects (AEs) were higher with the investigational regimen compared with rituximab plus GemOx, with patients receiving a median of 11 vs 4 cycles of treatment in each arm, respectively.1 One of the most common AEs was cytokine release syndrome, which was generally low grade (any grade, 44.2%; grade 1, 31.4%; grade 2, 10.5%; grade 3, 2.3%) and occurred primarily in the first cycle of treatment.

References

1. FDA accepts supplemental biologics license application for Genentech’s Columvi combination for people with relapsed or refractory diffuse large B-cell lymphoma. News release. Genentech. December 4, 2024. Accessed December 5, 2024. https://www.gene.com/media/press-releases/15045/2024-12-04/fda-accepts-supplemental-biologics-licen
2. FDA grants accelerated approval to glofitamab-gxbm for selected relapsed or refractory large B-cell lymphomas. FDA. Updated June 16, 2023. Accessed December 5, 2024. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-glofitamab-gxbm-selected-relapsed-or-refractory-large-b-cell
3. 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