Columvi Combination for Diffuse Large B-Cell Lymphoma Achieves Primary Endpoint of Overall Survival in Phase III Trial

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Data from the Phase III STARGLO trial (NCT04408638) show the combination of Columvi (glofitamab; Roche) with gemcitabine and oxaliplatin (GemOx) achieved the primary endpoint of overall survival (OS) in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) previously administered at least one line of therapy and who are not candidates for autologous stem cell transplant (ASCT).¹ In June 2023, the FDA granted accelerated approval to Columvi for patients with R/R DLBCL following two or more lines of prior systemic therapy based on findings from the Phase I/II NP30179 trial, after previously granting priority review status for this indication.²

“People with this aggressive lymphoma facing relapse or progression after initial treatment have limited options—particularly those who are ineligible for stem cell transplant,” said Levi Garraway, MD, PhD, Roche’s chief medical officer and head of Global Product Development. “Building on Columvi’s established benefits, these data demonstrate the potential of this combination regimen to improve survival outcomes in earlier lines of treatment.”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, thus dually targeting both cells. Columvi is the first 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 via 13 intravenous infusions over a maximum of 12 cycles, which includes step-up dosing, or until disease progression or intolerance to therapy, whichever occurs first. Following the first cycle, Columvi is administered once every three weeks.

The therapy 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.²

The multicenter, open-label, randomized STARGLO trial compared the efficacy and safety of Columvi plus GemOx versus MabThera/Rituxan (rituximab) plus GemOx in patients with DLBCL previously administered at least one line of therapy and who are not candidates for ASCT.¹

Exclusion criteria included failure of only one previous line of therapy and candidacy for stem cell transplantation; history of transformation of indolent disease to DLBCL; previous treatment with Columvi or other bispecific antibodies targeting both CD20 and CD3; prior administration of radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any novel agent to treat cancer within two weeks before first study treatment; and treatment with monoclonal antibodies within four weeks before first study treatment.³

The trial’s primary endpoint was OS, with secondary endpoints that included progression-free survival, complete response rate, objective response rate, duration of objective response, as well as safety and tolerability.³ In addition to achieving the trial’s primary endpoint of OS, the safety of the Columvi plus GemOx combination was consistent with the known safety profiles of the individual drugs.

In prior clinical trials, the most common adverse events associated with Columvi were cytokine release syndrome (CRS; 70%), musculoskeletal pain (21%), fatigue (20%) and rash (20%).

Roche said it will submit the data from the STARGLO trial to health authorities and will share it at an upcoming medical meeting.

References

1. Roche’s Columvi meets primary endpoint of overall survival in people with relapsed or refractory diffuse large B-cell lymphoma in Phase III STARGLO study. Roche. News release. April 15, 2024. Accessed April 15, 2024. https://www.roche.com/media/releases/med-cor-2024-04-15

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 April 15, 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 April 15, 2024. https://www.clinicaltrials.gov/study/NCT04408638