Genentech's STARGLO Study Shows Columvi Extends Survival in Relapsed/Refractory Diffuse Large B-cell Lymphoma

Genentech, a Roche Group subsidiary, has unveiled promising findings from its Phase III STARGLO study involving the drug Columvi (glofitamab-gxbm) combined with gemcitabine and oxaliplatin (GemOx). This study compared the effectiveness of this combination to a regimen of Rituxan (rituximab) and GemOx (R-GemOx) in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are either ineligible for autologous stem cell transplant or have undergone multiple prior treatments.

The study reached its primary endpoint, demonstrating a significant 41% reduction in the risk of death for patients receiving the Columvi combination compared to those on the R-GemOx regimen. This was presented at the European Hematology Association (EHA) 2024 Congress. Dr. Jeremy Abramson, principal investigator of the STARGLO study, emphasized the groundbreaking nature of these results, highlighting Columvi's potential to significantly improve survival in second or later-line DLBCL treatment for patients who lack other viable options.

The primary analysis, conducted with a median follow-up of 11.3 months, confirmed a notable improvement in overall survival (OS) for the Columvi group. The median OS was not reached for the Columvi-treated patients, contrasting starkly with the nine months observed in the R-GemOx group. The safety profile of the Columvi combination was consistent with the known profiles of the individual drugs.

Secondary endpoints were also promising, with a 63% reduction in the risk of disease progression or death (progression-free survival, PFS) in the Columvi group compared to the R-GemOx group. A follow-up analysis, with a median follow-up of 20.7 months, reinforced these results, showing a median OS of 25.5 months for the Columvi group versus 12.9 months for the R-GemOx group. Additionally, more patients in the Columvi group achieved a complete response (58.5% vs. 25.3%).

Despite these positive outcomes, the Columvi combination exhibited higher adverse event (AE) rates compared to R-GemOx, likely due to the longer duration of treatment cycles (11 cycles for Columvi versus 4 for R-GemOx). One of the most common adverse events was cytokine release syndrome, primarily occurring in the first treatment cycle and generally of low grade.

This study marks the first instance where a CD20xCD3 bispecific antibody has shown a survival benefit in a randomized Phase III trial for DLBCL. Historically, standard second-line therapy for R/R DLBCL patients has involved high-dose chemotherapy followed by stem-cell transplant, but many patients are not suitable for this due to age or other health conditions. Newer treatments are emerging, yet barriers remain, and alternative options like Columvi are needed.

The STARGLO study's findings will be submitted to global health authorities, including the U.S. FDA and the European Medicines Agency. Furthermore, Columvi is being investigated for other aggressive lymphomas and has recently received Breakthrough Therapy Designation from the FDA for treating relapsed or refractory mantle cell lymphoma.

Columvi functions as a CD20xCD3 T-cell engaging bispecific antibody that targets both T cells and B cells, facilitating the destruction of cancerous B cells. It is currently approved for treating certain types of diffuse large B-cell lymphoma and large B-cell lymphoma in adults who have relapsed or are refractory to previous treatments.

Genentech, with over two decades of dedication to hematology, continues to push the boundaries in developing innovative treatments for blood diseases, aiming to provide new hope for patients with serious conditions.