Columvi Combination Shows Significant Survival Benefit Treating R/R DLBCL in Phase III STARGLO trial

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The combination of Columvi (glofitamab; Roche) with gemcitabine and oxaliplatin (GemOx) produced statistically significant and clinically meaningful results treating relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) in the Phase III STARGLO trial (NCT04408638).¹ Investigators evaluated the Columvi combination in comparison to MabThera/Rituxan (rituximab) in combination with GemOx (R-GemOx) in the treatment of patients with R/R DLBCL previously administered at least one line of therapy and who are not candidates for autologous stem cell transplant (ASCT), or who were previously administered two or more lines of therapy.

"The results from STARGLO are the first to show the potential of a CD20xCD3 bispecific antibody to make a difference in second or later-line DLBCL in people who are ineligible for transplant and have limited options," principal trial investigator Jeremy Abramson, MD, director, Jon and Jo Ann Hagler Center for Lymphoma at the Massachusetts General Hospital Cancer Center, said in a press release. "[Columvi] in combination with GemOx showed clinically significant improvement in overall survival, as well as key secondary endpoints, and the benefits were reinforced with an additional 11 months of follow-up.”¹

Columvi, a CD20xCD3 T-cell engaging bispecific antibody, targets CD3, a protein found on the surface of immune T cells, and CD20, a healthy or malignant protein that lines the surfaces of B cells. Columvi activates the T cell proteins to kill cancer cells on the B cell, thereby dually targeting both cells. Columvi was the first FDA-approved therapy of its kind that is fixed-duration, off-the-shelf, and effective for patients with multiple treatments, according to Roche.²

Columvi is administered as 13 intravenous infusions over a maximum of 12 cycles, including step-up dosing, or until disease progression or intolerance to therapy, whichever occurs first. After the first cycle is completed, Columvi is administered once every three weeks. It is designed to be completed in approximately 8.5 months, offering patients with R/R DLBCL a target end date for the treatment course and the potential for a treatment-free period.³

The multicenter, open-label, randomized STARGLO trial compared the efficacy and safety of Columvi plus GemOx versus MabThera/Rituxan plus GemOx in patients with DLBCL previously administered at least one line of therapy and who are not candidates for ASCT.

The primary endpoint of the trial is overall survival (OS), with secondary endpoints that include progression-free survival, complete response (CR) rate, objective response rate, duration of objective response, as well as safety and tolerability.² The confirmatory trial seeks to convert the accelerated approval granted by the FDA in June 2023 to a full approval for this indication.

The latest results from the trial show that at a median follow-up of 11.3 months, the primary OS endpoint was achieved, showing that patients administered Columvi plus GemOx had a 41% lower risk of death (hazard ratio [HR]=0.59, 95% CI: 0.40-0.89, p=0.011) compared with R-GemOx.1 Median OS was not yet reached in patients administered the Columvi combination compared with nine months in the R-GemOx cohort.

A follow-up analysis conducted after all patients had completed therapy at a median follow-up of 20.7 months demonstrated a continued benefit in the trial’s primary and secondary endpoints. Median OS in the Columvi combination cohort was 25.5 months compared with 12.9 months in the R-GemOx cohort. Further, 58.5% of patients in the Columvi combination cohort achieved a CR compared with 25.3% in the R-GemOx cohort.

In terms of safety, adverse events (AEs) associated with the Columvi combination were consistent with the previously established profiles of the individual therapies, with no new safety signals reported. AE rates were higher in the Columvi combination cohort than in the R-GemOx cohort, with a higher median number of cycles administered with the Columvi combination at 11 compared to four with R-GemOx. Cytokine release syndrome was among the most frequently reported AEs and primarily was reported during cycle one of treatment (any grade: 44.2%, grade 1: 31.4%, grade 2: 10.5%, grade 3: 2.3%).

“This marks a first step in advancing Columvi combinations in earlier settings to address the urgent need for the 40% of people who will relapse or have refractory disease and who have limited options,” said Levi Garraway, MD, PhD, Roche chief medical officer and head of Global Product Development, in the release. “Moreover, patients do not have to wait to start treatment with Columvi. This could be particularly important for patients with highly aggressive disease who are at risk of rapid disease progression.”¹

References

1. Roche’s Phase III STARGLO study demonstrates Columvi significantly extends survival in people with relapsed or refractory diffuse large B-cell lymphoma. News release. Roche. June 15, 2024. Accessed June 19, 2024. https://www.roche.com/media/releases/med-cor-2024-06-15

2. 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. Genentech. News release. June 16, 2023. Accessed June 19, 2024. https://www.gene.com/media/press-releases/14994/2023-06-15/fda-approves-genentechs-columvi-the-firs

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 identifier: NCT04408638. Updated April 8, 2024. Accessed June 19, 2024. https://www.clinicaltrials.gov/study/NCT04408638