Updated STARGLO Data Show Maintained OS Benefit With Glofitamab Plus Chemo in R/R DLBCL

R/R DLBCL | Image Credit:

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Treatment with the combination of glofitamab-gxbm (Columvi), gemcitabine, and oxaliplatin (GemOx) led to a statistically significant and clinically meaningful improvement in overall survival (OS) compared with rituximab (Rituxan) plus GemOx in patients with relapsed/refractory diffuse large B-cell lymphoma who have received at least one prior line of therapy and are not candidates for autologous stem cell transplant (ASCT), according to 2-year follow-up data from the phase 3 STARGLO trial (NCT04408638).1

Findings announced by Genetech showed that at a median follow-up of 24.7 months, patients treated with glofitamab plus GemOx achieved a median OS that was not reached (NR) compared with 13.5 months, translating to a 40% improvement in OS.

Full data from this analysis will be presented at the 2025 ASCO Annual Meeting.

"When cancer comes back or doesn’t respond to treatment, it’s devastating for patients with DLBCL given the aggressive nature of the disease,” Haifaa Abdulhaq, MD, a professor at the University of California San Francisco (UCSF) and director of Hematology at UCSF Fresno, stated in a news release. “In my community practice, I’ve seen the potential of this [glofitamab] combination to help patients start treatment quickly—providing lasting remissions and more time without ongoing therapy.”

In December 2024, the FDA accepted a supplemental biologics license application (sBLA)seeking the approval of glofitamab plus GemOx for the treatment of patients with relapsed/refractory DLBCL who have received at least 1 prior line of therapy and who are not candidates for ASCT.2 The submission was supported by prior data from STARGLO.

However, on May 20, 2025, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 8 to 1 against the applicability of the patient population and results from STARGLO to the United States population of patients with relapsed/refractory DLBCL.3 In the study’s intention-to-treat (ITT) population (n = 274), 9% of patients (n = 25) were from North America, 32% (n = 88) were from Europe, 11% (n = 30) were from Australia, and 48% (n = 131) were from Asia.4

A subgroup analysis from the study presented by the FDA during the ODAC meeting showed that OS benefits differed for glofitamab plus GemOx among patients from Europe (glofitamab arm, n = 62; rituximab arm, n = 26; HR, 1.09; 95% CI, 0.54-2.18), patients from North America (glofitamab arm, n = 15; rituximab arm, n = 10; HR, 2.62; 95% CI, 0.56-12.34), and patients from the rest of the world (glofitamab arm, n = 106; rituximab arm, n = 55; HR, 0.41; 95% CI, 0.27-0.64).

Data from the primary analysis of STARGLO published in The Lancet showed that at median follow-up of 11.3 months (95% CI, 9.6-12.7), patients treated with glofitamab plus GemOx (n = 183) achieved a median OS that was not estimable (NE; 95% CI, 13.8-NE) compared with 9.0 months (95% CI, 7.3-14.4) for those given rituximab plus GemOx (n = 91; HR, 0.59; 95% CI, 0.40-0.89; P = .011).5

In June 2023, the FDA granted accelerated approval to glofitamab for the treatment of adult patients with relapsed/refractory DLBCL not otherwise specified or large B-cell lymphoma arising from follicular lymphoma after at least 2 lines of systemic therapy.6

STARGLO Breakdown

The open-label, multicenter study enrolled patients at least 18 years of age with histologically confirmed relapsed/refractory DLBCL who received at least 1 prior line of systemic therapy and were not candidates for high-dose chemotherapy and ASCT.7 Other key inclusion criteria comprised an ECOG performance status of 0 to 2 and adequate hematological and renal function.

Patients with a history of transformation of indolent disease to DLBCL were excluded, as were those with high-grade B-cell lymphoma with MYC, BCL2, and/or BCL6 rearrangements, high-grade B-cell lymphoma not otherwise specified, and primary mediastinal B-cell lymphoma. Primary or secondary central nervous system (CNS) lymphoma, a history of CNS lymphoma, and current or a history of CNS disease, also precluded patients from enrollment.

Patients were randomly assigned 1:1 to receive 8 cycles of glofitamab in combination with GemOx, followed by up to 4 cycles of glofitamab monotherapy; or rituximab plus GemOx for up to 8 cycles. Notably, those in the experimental arm received a single dose of obinutuzumab 7 days prior to the first dose of glofitamab.

OS served as the trial’s primary end point. Secondary end points included progression-free survival, complete response (CR) rate, objective response rate, duration of response, quality of life, and safety.

Additional data from the updated analysis announced by Genentech showed that the glofitamab regimen reduced the risk of disease progression or death by 59% in the ITT population (HR, 0.41; 95% CI, 0.29-0.58).1 The CR rates were 58.5% and 25.3% in the glofitamab and rituximab arms, respectively.

Safety findings for the glofitamab-based combination were consistent with previous analysis and the known safety profiles of the individual agents.

References

1. New two-year follow-up of Genentech’s Columvi extends overall survival in relapsed or refractory diffuse large B-bell lymphoma patients. News release. Genentech. May 22, 2025. Accessed May 23, 2025. https://www.gene.com/media/press-releases/15063/2025-05-22/new-two-year-follow-up-of-genentechs-col
2. 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 May 23, 2025. https://www.gene.com/media/press-releases/15045/2024-12-04/fda-accepts-supplemental-biologics-licen
3. May 20, 2025, Meeting of the Oncologic Drugs Advisory Committee (ODAC). FDA. https://www.youtube.com/live/iSGFdhMgh1E
4. Glofitamab-gxbm FDA opening remarks. FDA. May 20, 2025. Accessed May 23, 2025. https://www.fda.gov/media/186557/download
5. 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
6. FDA approves Genentech’s Columvi, the first and only bispecific antibody with a fixed-duration treatment for people with relapsed or refractory diffuse large B-cell lymphoma. News release. Genentech. June 15, 2023. Accessed May 23, 2025. https://www.gene.com/media/press-releases/14994/2023-06-15/fda-approves-genentechs-columvi-the-firs
7. 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 April 13, 2025. Accessed May 23, 2025. https://www.clinicaltrials.gov/study/NCT04408638