Key Takeaways
- FDA Panel Votes Against Columvi-GemOx sBLA
The FDA’s Oncologic Drugs Advisory Committee (ODAC) declined to recommend approval of Columvi (glofitamab) plus GemOx for relapsed/refractory (R/R) DLBCL in patients ineligible for stem cell transplant, citing limited applicability of STARGLO trial data to the US population. - STARGLO Trial Shows Significant Survival Benefit
The Phase III STARGLO trial demonstrated a 41% reduction in risk of death and doubled median overall survival (25.5 vs. 12.9 months) for patients treated with the Columvi-GemOx combination compared to R-GemOx, supporting regulatory approvals outside the US. - Multiregional Trial Design Raises Generalizability Concerns
ODAC members expressed concerns over regional differences in treatment efficacy, noting that a large Asian patient subgroup may have driven the overall survival benefit, raising questions about relevance to US-based clinical practice.
Citing limited applicability of data from the Phase III STARGLO trial (NCT04408638), the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted against recommending approval of a supplemental Biologics License Application (sBLA) for Columvi (glofitamab) in combination with gemcitabine and oxaliplatin (GemOx) for the treatment of relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) in patients who are ineligible for autologous stem cell transplant (ASCT).1,2
ODAC Raises Concerns Over STARGLO Trial's Relevance to US DLBCL Patients
Although the STARGLO trial demonstrated a statistically significant overall survival (OS) benefit in patients administered the Columvi-GemOx combination, ODAC raised concerns regarding the applicability of the results from the multiregional clinical trial (MRCT) to the total US patient population.
“Columvi in combination with GemOx demonstrated a 41% reduction in risk of death in a phase III, randomised, multiregional clinical trial, supporting its recent approval by the European Commission and inclusion in the US National Comprehensive Cancer Network treatment guidelines as a category 1 preferred regimen,” Levi Garraway, MD, PhD, Roche chief medical officer and head of Global Product Development, said in a press release. “We believe the STARGLO results are applicable to US patients, with the global study population closely mirroring the real-world clinical profile of DLBCL patients in the US, and we will continue working with the FDA on the regulatory path forward.”1
Columvi-GemOx Shows Promising Survival Benefit Treating Diffuse Large B-cell Lymphoma
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 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
STARGLO Trial Design and Methodology
- 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 MRCT enrolled 274 patients at 62 sites across 13 countries, with 52% of patients enrolled outside of Asia.
- Patients were randomly assigned in a 2:1 ratio to receive Columvi at step-up dosing to 30 mg plus gemcitabine at 1000 mg/m2 and oxaliplatin at 100 mg/m2 for eight cycles, followed by four cycles of Columvi monotherapy; or Rituxan (rituximab) at 375 mg/m2 plus GemOx for eight cycles.
- The primary endpoint of the trial is 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.
- The confirmatory trial seeks to convert the accelerated approval granted by the FDA in June 2023 to a full approval for this indication.
STARGLO Phase III Trial Demonstrates Significant Survival Benefit for Columvi-GemOx
- Interim data from the trial released in June 2024 show that at a median follow-up of 11.3 months, the primary OS endpoint was achieved, as 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.
- Median OS was not yet reached in patients administered the Columvi combination compared with nine months in the R-GemOx cohort.4
- 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.
FDA Committee Questions Regional Variability in Multiregional Trial Results
ODAC voted 8-1 against the sBLA, identifying concerns with the STARGLO data based on the enrollment of the MRCT that included a large Asian population and limited US patient population. The committee also cited inconsistent efficacy findings for the different regional subgroups.5
“The treatment effect across all efficacy end points was inconsistent between the Asian and non-Asian regional subgroups,” Nicole Sunseri, MD, PhD, FDA Division of Hematologic Malignancies in the Office of Oncologic Diseases, said during the meeting. “Given the size of the Asian subgroup and the magnitude of the treatment effect, it is likely that the overall study results are being driven by the Asian regional subgroup.”6
Genentech and Clinical Experts Defend Applicability of Global STARGLO Data
Manufacturer Genentech, a subsidiary of Roche, countered that the findings from the overall trial population are generalizable to the US population. The FDA is expected to issue a decision on approval of the sBLA by July 20, 2025.
“Many of the patients with DLBCL who I see in my clinic are similar to the patients reflected in this study, making the glofitamab-GemOx regimen an important potential treatment option,” said Krish Patel, MD, director of Lymphoma Research, Sarah Cannon Research Institute, said in a company press release. “These patients need more effective, readily available treatment options and the compelling results from STARGLO deliver on this need.”1
References
1. Roche provides update on FDA Advisory Committee meeting on Columvi combination for people with relapsed or refractory diffuse large B-cell lymphoma. News release. Roche. May 19, 2025. Accessed May 21, 2025. https://www.roche.com/media/releases/med-cor-2025-05-20
2. 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 13, 2025. Accessed May 21, 2025. https://www.clinicaltrials.gov/study/NCT04408638
3. 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 May 21, 2025. https://www.gene.com/media/press-releases/14994/2023-06-15/fda-approves-genentechs-columvi-the-firs
4. 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 May 21, 2025. https://www.roche.com/media/releases/med-cor-2024-06-15
5. Glofitamab-gxbm FDA opening remarks. FDA. May 20, 2025. Accessed May 21, 2025. https://www.fda.gov/media/186557/download
6. Meeting of the Oncologic Drugs Advisory Committee (ODAC). FDA. May 20, 2025. Accessed May 21, 2025. https://www.youtube.com/live/iSGFdhMgh1E
