Roche announced statistically significant results from its Phase III STARGLO study demonstrating that Columvi (glofitamab) in combination with gemcitabine and oxaliplatin significantly improved survival outcomes in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The data were presented at the European Hematology Association (EHA) 2024 Congress as a late-breaking oral presentation.
Primary Endpoint Achievement
The study met its primary endpoint of overall survival, showing a 41% reduction in the risk of death (hazard ratio 0.59, 95% CI: 0.40-0.89, p=0.011) for patients treated with Columvi plus GemOx versus rituximab plus GemOx (R-GemOx). At the primary analysis with a median follow-up of 11.3 months, median overall survival was not reached in the Columvi arm compared to nine months for the control group.
A follow-up analysis conducted after all patients completed therapy, with a median follow-up of 20.7 months, demonstrated continued benefit. Median overall survival for the Columvi combination reached 25.5 months, nearly double the 12.9 months observed with R-GemOx.
"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," said Jeremy Abramson, M.D., Director of the Jon and Jo Ann Hagler Center for Lymphoma at Massachusetts General Hospital Cancer Center and principal investigator of the study.
Secondary Endpoints and Response Rates
The Columvi combination also achieved significant improvements in secondary endpoints. Progression-free survival showed a 63% reduction in risk of disease worsening or death compared to R-GemOx (HR=0.37; 95% CI: 0.25–0.55, p<0.0001). Complete response rates were more than twice as high with the Columvi regimen at 58.5% versus 25.3% for the control arm.
Safety Profile and Regional Considerations
Adverse event rates were higher with the Columvi combination, noting that patients received a higher median number of treatment cycles (11 versus 4). Cytokine release syndrome was among the most common adverse events, occurring in 44.2% of patients but generally presenting as low grade (Grade 1: 31.4%, Grade 2: 10.5%, Grade 3: 2.3%) and primarily during the first cycle.
Serious adverse events were more frequent in the Columvi arm (54% versus 17%), with fatal adverse events related to treatment occurring in 3% of Columvi patients compared to 1% in the rituximab group. Seven COVID-related deaths occurred in the Columvi cohort (4% rate) versus none with rituximab.
Regional analysis revealed some inconsistencies, with the overall survival benefit appearing to be driven primarily by patients enrolled outside the US and Europe, who comprised 59% of the 274-patient population. However, Roche noted that interpretation of these regional differences is limited given the exploratory nature of the analysis and small subgroup sizes with wide confidence intervals.
Clinical Significance and Market Impact
Columvi represents the first CD20xCD3 bispecific antibody to demonstrate a survival benefit in DLBCL in a randomized Phase III trial. The drug received accelerated US approval for third-line or later DLBCL in 2023, and these confirmatory results will support submissions to global health authorities for full approval conversion.
"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, M.D., Ph.D., Roche's Chief Medical Officer and Head of Global Product Development.
Treatment Landscape and Unmet Need
DLBCL is the most common form of non-Hodgkin lymphoma, accounting for approximately one-third of NHL cases. While generally responsive to frontline treatment, up to 40% of patients experience relapse or refractory disease, at which point salvage therapy options are limited and survival is short. Approximately 160,000 people worldwide are diagnosed with DLBCL annually.
The standard second-line therapy for relapsed/refractory DLBCL patients has historically been high-dose chemotherapy followed by stem cell transplant, but many patients are ineligible due to age or comorbidities. Columvi offers a fixed-duration treatment option, providing patients with a defined treatment endpoint and the possibility of treatment-free periods.
Regulatory Path Forward
Results from the STARGLO study will be submitted to the FDA and European Medicines Agency to support conversion from accelerated to full approval. The data position Roche favorably in the competitive CD20 bispecific landscape, particularly as other companies face regulatory challenges with their competing programs.
Columvi is also being investigated in other aggressive lymphomas and recently received FDA Breakthrough Therapy Designation for relapsed or refractory mantle cell lymphoma based on Phase I/II study results.
