Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced compelling results from its Phase III STARGLO study of Columvi® (glofitamab-gxbm) in combination with gemcitabine and oxaliplatin (GemOx) compared to Rituxan® (rituximab) plus GemOx (R-GemOx) for patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). These patients had previously undergone at least one line of therapy and were ineligible for autologous stem cell transplant, or had undergone two or more lines of therapy. The findings were presented in a Plenary Abstracts Session at the European Hematology Association (EHA) 2024 Congress as a late-breaking oral presentation and highlighted in the congress Press Briefing.
“The STARGLO study results are the first to demonstrate the potential of a CD20xCD3 bispecific antibody to impact second or later-line DLBCL in patients who are ineligible for transplant and have few alternatives,” 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 STARGLO study. “Glofitamab with GemOx significantly improved overall survival and key secondary endpoints, with benefits sustained through an additional 11 months of follow-up.”
The primary analysis, with a median follow-up of 11.3 months, confirmed the study met its primary endpoint of overall survival (OS). Patients treated with Columvi plus GemOx showed a significant survival advantage, with a 41% reduction in the risk of death (hazard ratio [HR]=0.59, 95% CI: 0.40-0.89, p=0.011) compared to R-GemOx. Median OS was not reached for the Columvi regimen, versus nine months for R-GemOx. The safety profile of the combination was consistent with the known safety profiles of the individual drugs.
Pre-specified exploratory subgroup analyses showed consistent results across clinically relevant factors such as line of therapy (second-line vs. third-line+) and outcome of last therapy (relapsed vs. refractory), despite some regional inconsistencies due to the exploratory nature and small sample sizes.
“This represents a pivotal advancement in Columvi combinations in earlier treatment settings, addressing the urgent need for the 40% of people who relapse or have refractory disease with limited options,” said Levi Garraway, M.D., Ph.D., Genentech’s Chief Medical Officer and Head of Global Product Development. “Patients can begin Columvi treatment immediately, which is crucial for those with highly aggressive disease at risk of rapid progression.”
The Columvi combination also achieved its key secondary endpoints, reducing the risk of disease worsening or death (progression-free survival, PFS) by 63% compared to R-GemOx (HR=0.37; 95% CI: 0.25–0.55, p<0.0001). A follow-up analysis, conducted after all patients had completed therapy (median follow-up of 20.7 months), showed continued benefits for both primary and secondary endpoints. Median OS for patients treated with Columvi was 25.5 months, compared to 12.9 months for R-GemOx, and more than twice as many patients achieved a complete response (58.5% vs. 25.3%, respectively).
Adverse event (AE) rates were higher with the Columvi combination compared to R-GemOx, with a higher median number of cycles received (11 vs. 4). Cytokine release syndrome was one of the most common AEs, generally low grade and occurring primarily in Cycle 1 (Any Grade: 44.2%, Grade 1: 31.4%, Grade 2: 10.5%, Grade 3: 2.3%).
Columvi is the first CD20xCD3 bispecific antibody to demonstrate a survival benefit in DLBCL in a randomized Phase III trial, showcasing its potential to improve survival outcomes in earlier lines of treatment. Standard second-line therapy for R/R DLBCL patients has traditionally been high-dose chemotherapy followed by stem-cell transplant, but not all patients are candidates due to age or comorbidities. Columvi offers a fixed-duration treatment, giving patients with R/R DLBCL a treatment end date and the possibility of a treatment-free period, unlike continuous treatments.
Results from the STARGLO study will be submitted to global health authorities, including the U.S. Food and Drug Administration (FDA) and the European Medicines Agency.
Columvi is also being studied in other aggressive, hard-to-treat lymphomas and was recently granted Breakthrough Therapy Designation by the FDA for the treatment of adult patients with relapsed or refractory mantle cell lymphoma who have received at least two prior therapies, based on results from the Phase I/II NP30179 study.
About Genentech
Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California.
About the STARGLO Study
The STARGLO study [GO41944; NCT04408638] is a Phase III, multicenter, open-label, randomized study evaluating the efficacy and safety of Columvi® (glofitamab-gxbm) in combination with gemcitabine plus oxaliplatin (GemOx) versus Rituxan® (rituximab) in combination with GemOx in patients with relapsed or 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, or who have received two or more prior lines of therapy. Outcome measures include overall survival (primary endpoint), progression-free survival, complete response rate, objective response rate, duration of objective response (secondary endpoints), and safety and tolerability.
STARGLO is intended as a confirmatory study to convert Columvi’s accelerated approval in the U.S. and conditional marketing authorization in the EU to full approvals for people with R/R DLBCL after two or more lines of systemic therapy based on the pivotal Phase I/II NP30179 study.
About Diffuse Large B-Cell Lymphoma
Diffuse large B-cell lymphoma (DLBCL) is an aggressive (fast-growing) blood cancer and is the most common form of non-Hodgkin’s lymphoma (NHL) in the U.S. While many people with DLBCL are responsive to treatment, the majority of those who relapse or are refractory to subsequent treatments have poor outcomes. DLBCL not otherwise specified is the most common category of large B-cell lymphoma (LBCL) and accounts for about 80% or more of cases. It applies to cases that do not fall into any specific disease subgroups of LBCL.
About Columvi® (glofitamab-gxbm)
Columvi is a CD20xCD3 T-cell engaging bispecific antibody designed to target CD3 on the surface of T cells and CD20 on the surface of B cells. Columvi was designed with a novel 2:1 structural format. This T-cell engaging bispecific antibody is engineered to have one region that binds to CD3, a protein on T cells, a type of immune cell, and two regions that bind to CD20, a protein on B cells, which can be healthy or malignant. This dual-targeting brings the T cell in close proximity to the B cell, activating the release of cancer cell-killing proteins from the T cell. A clinical development program for Columvi is ongoing, investigating the molecule as a monotherapy and in combination with other medicines for the treatment of people with B-cell non-Hodgkin’s lymphomas, including diffuse large B-cell lymphoma and other blood cancers.