Roche announced statistically significant and clinically meaningful results from its Phase III STARGLO study of Columvi® (glofitamab) in combination with gemcitabine and oxaliplatin (GemOx) versus MabThera®/Rituxan® (rituximab) in combination with GemOx (R-GemOx) for people with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) 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. Data were featured in the congress Press Briefing and presented on June 15, 2024 in the Plenary Abstracts Session at the European Hematology Association (EHA) 2024 Congress as a late-breaking oral presentation. The primary analysis (median follow-up of 11.3 months) confirmed that the study met its primary endpoint of overall survival (OS), demonstrating that patients treated with Columvi plus GemOx lived significantly longer, with a 41% reduction in the risk of death (hazard ratio [HR]=0.59, 95% CI: 0.40-0.89, p=0.011) versus R-GemOx.1 Median OS was not reached with the Columvi regimen versus nine months for R-GemOx.1 Safety of the combination appeared consistent with the known safety profiles of the individual medicines.

Pre-specified exploratory subgroup analyses showed comparable results, including consistency across the clinically relevant stratification factors of line of therapy (second-line versus third-line+) and outcome of last therapy (relapsed versus refractory). Regional inconsistencies were observed, however interpretation is limited given the exploratory nature of these analyses and small subgroups with wide confidence intervals. The Columvi combination also met its key secondary endpoints, with a 63% reduction in risk of disease worsening or death (progression-free survival, PFS) compared to R-GemOx (HR=0.37; 95% CI: 0.25?0.55, p<0.0001).

A follow-up analysis was conducted after all patients had completed therapy (median follow-up of 20.7 months), which showed continued benefit in both primary and secondary endpoints. Median OS for people treated with the Columvi combination was 25.5 months, nearly double what was seen for people treated with R-GemOx at 12.9 months, and more than twice as many patients experienced a complete response (58.5% versus 25.3%, respectively). Adverse event (AE) rates were higher with the Columvi combination versus R-GemOx, noting higher median number of cycles received with Columvi combination (11 versus 4).

One of the most common AEs was cytokine release syndrome, which was generally low grade (Any Grade: 44.2%, Grade 1: 31.4%, Grade 2: 10.5%, Grade 3: 2.3%) and occurred primarily in Cycle 1. Columvi is the first CD20xCD3 bispecific antibody to demonstrate a survival benefit in DLBCL in a randomised Phase III trial, demonstrating the potential of this type of therapeutic combination to improve survival outcomes in earlier lines of treatment. The standard second-line therapy for R/R DLBCL patients has historically been high-dose chemotherapy followed by stem-cell transplant, however, not everyone with R/R DLBCL is a candidate due to age or coexisting medical conditions. Newer therapies are also becoming available, but barriers remain for many, and alternative treatment options are needed for these patients.

Columvi is given as a fixed-duration treatment, offering people 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. The STARGLO study [GO41944; NCT04408638] is a Phase III, multicentre, open-label, randomised study evaluating the efficacy and safety of Columvi® (glofitamab) in combination with gemcitabine plus oxaliplatin (GemOx) versus MabThera®/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 who 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 US and conditional marketing authorisation 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. 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.

Columvi is part of Roche?s broad and industry-leading CD20xCD3 T-cell-engaging bispecific antibody clinical development programme that also includes Lunsumio® (mosunetuzumab), which aims to provide tailored treatment options that suit the diverse needs, preferences, and experiences of people with blood cancers and healthcare systems. Roche is investigating Columvi as a monotherapy and in combination with other medicines for the treatment of diffuse large B-cell lymphoma (DLBCL) and other blood cancers. This includes the Phase III SKYGLO [NCT06047080] trial investigating Columvi in combination with Polivy® (polatuzumab vedotin), MabThera®/Rituxan® (rituximab), cyclophosphamide, doxorubicin and prednisone in previously untreated DLBCL. DLBCL is the most common form of non-Hodgkin lymphoma (NHL), accounting for about one in three cases of NHL.

DLBCL is an aggressive (fast-growing) type of NHL. While it is generally responsive to treatment in the frontline, as many as 40% of people will relapse or have refractory disease, at which time salvage therapy options are limited and survival is short. Improving treatments earlier in the course of the disease and providing much needed alternative options could help to improve long-term outcomes.

Approximately 160,000 people worldwide are diagnosed with DLBCL each year.