Roche's Phase III STARGLO study shows Columvi extends survival in relapsed or refractory diffuse large B-cell lymphoma

Roche recently announced promising results from their Phase III STARGLO study, which evaluated the efficacy of Columvi® (glofitamab) combined with gemcitabine and oxaliplatin (GemOx) against the standard treatment of rituximab with GemOx (R-GemOx) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The study, presented at the European Hematology Association (EHA) Congress 2024, revealed that the Columvi combination significantly improved overall survival rates, reducing the risk of death by 41% compared to R-GemOx.

Dr. Jeremy Abramson, principal investigator of the STARGLO study, highlighted the potential of the Columvi regimen. He noted that the combination showed a clinically significant improvement in overall survival and key secondary endpoints, reinforced by an additional follow-up of 11 months. The primary analysis showed that patients treated with Columvi and GemOx lived significantly longer, presenting a hazard ratio of 0.59 and a median overall survival that was not reached, compared to nine months for R-GemOx.

Safety profiles of the combined treatment were in line with expectations from individual drugs. The study also demonstrated consistency in results across various subgroups, though some regional inconsistencies were noted. Dr. Levi Garraway, Roche’s Chief Medical Officer, emphasized the importance of the findings, particularly for patients with highly aggressive disease who need immediate treatment options.

The secondary endpoints were equally promising, with Columvi-GemOx showing a 63% reduction in the risk of disease progression or death compared to R-GemOx. The follow-up analysis, with a median of 20.7 months, confirmed continued benefits in both primary and secondary endpoints. Patients treated with the Columvi combination had a longer median overall survival of 25.5 months versus 12.9 months for R-GemOx, and a higher rate of complete response (58.5% versus 25.3%).

Adverse events (AEs) were more frequent in patients receiving the Columvi combination, but this was associated with a higher median number of treatment cycles. The most common AE was cytokine release syndrome, mostly low grade and occurring primarily in the first cycle.

Columvi is the first CD20xCD3 bispecific antibody to demonstrate a survival benefit in a randomized Phase III trial for DLBCL. This type of treatment could offer new options for patients who are ineligible for stem-cell transplants. The study results will be submitted to global health authorities, including the FDA and the European Medicines Agency, for potential approval.

Roche is also investigating Columvi in other aggressive lymphomas and recently received Breakthrough Therapy Designation from the FDA for relapsed or refractory mantle cell lymphoma based on earlier study results. The STARGLO study aims to convert Columvi’s accelerated approval in the US and conditional marketing authorization in the EU to full approvals for patients with relapsed or refractory DLBCL, given the positive data from this and previous studies.

Columvi’s design involves a novel 2:1 structural format that targets CD3 on T-cells and CD20 on B-cells, promoting the immune system's ability to kill cancer cells. Roche’s broader development program includes other bispecific antibodies like Lunsumio®, aiming to offer tailored treatments for various blood cancers.

DLBCL, the most common form of non-Hodgkin lymphoma, remains a challenge with a high relapse rate. The findings from the STARGLO study represent a significant step forward in treating this aggressive cancer, offering hope for improved long-term outcomes for many patients worldwide.