The DLBCL market is becoming more competitive owing to the introduction of recently approved therapies in the first-line setting, expansion of CAR-T therapies in earlier lines (2nd-line), and entrance of bispecific antibodies in the R/R setting. The space beyond the third-line plus setting has recently gained popularity as a result of the expansion of the labels of approved drugs into earlier lines. 

COLUMVI is the first CD20 x CD3 bispecific antibody to show a survival benefit in DLBCL in a randomized Phase III trial, highlighting the potential of this therapeutic combination to enhance survival outcomes in earlier treatment lines. The standard second-line therapy for R/R DLBCL patients has historically been high-dose chemotherapy followed by stem-cell transplant, however, not all R/R DLBCL patients are suitable candidates due to factors such as age or existing medical conditions. Although newer therapies are emerging, many patients still face barriers, necessitating alternative treatment options. COLUMVI offers a fixed-duration treatment, providing R/R DLBCL patients with a defined end to treatment and the potential for a treatment-free period, in contrast to continuous treatments.

Efficacy and safety results of Glofit-GemOx in patients with R/R DLBCL after ≥1 prior line of therapy from the Phase III STARGLO trial were presented at the EHA 2024 Congress as a late-breaking oral presentation.

The STARGLO study is a Phase III trial assessing the efficacy and safety of COLUMVI combined with gemcitabine plus oxaliplatin (GemOx) in patients with relapsed or refractory DLBCL who have undergone at least one prior line of therapy and are ineligible for autologous stem cell transplant, or those who have received two or more prior lines of therapy. As per Roche, the results from this study will be submitted to global health authorities, including the US FDA and EMA. STARGLO is intended as a confirmatory study to convert COLUMVI’s accelerated approval in the US, granted by the FDA in June 2023, and its conditional marketing authorization in the EU to full approvals for those with R/R DLBCL after two or more lines of systemic therapy, based on the pivotal Phase I/II NP30179 study.

The primary analysis (median follow-up of 11.3 months) confirmed that the study met its primary endpoint, demonstrating that patients treated with COLUMVI plus GemOx had a significantly longer overall survival (OS) with a 41% reduction in the risk of death compared to R-GemOx. Median OS was not reached with COLUMVI but was 9.0 months for R-GemOx. The safety profile was consistent with known profiles of the individual drugs.

Exploratory subgroup analyses showed consistent results across therapy lines (second-line versus third-line+) and outcomes of the last therapy (relapsed versus refractory), despite regional inconsistencies. The COLUMVI combination also met key secondary endpoints, showing a 63% reduction in the risk of disease progression or death (PFS) compared to R-GemOx. A follow-up analysis (median follow-up of 20.7 months) confirmed continued benefit in both primary and secondary endpoints, with median OS for COLUMVI at 25.5 months versus 12.9 months for R-GemOx, median PFS of 13.8 and 3.6 months for COLUMVI and R-GemOx, respectively, and a higher complete response rate (58.5% versus 25.3%).

Adverse events (AEs) rates were higher with the COLUMVI combination versus R-GemOx, noting higher median number of cycles received with COLUMVI combination. One of the most common AEs was cytokine release syndrome, which was generally low grade and occurred primarily in Cycle 1.

KOL insights

“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. Glofitamab in combination with GemOx showed clinically significant improvement in overall survival, as well as key secondary endpoints, and the benefits were reinforced with an additional 11 months of follow-up.” – MD, United States

Conclusion 

DLBCL, the most prevalent form of non-Hodgkin lymphoma, accounts for about one-third of NHL cases. As per DelveInsight, there were nearly 76,100 incident cases of DLBCL in the 7MM. Although it is initially responsive to frontline treatment, up to 40% of patients experience relapse or refractory disease, where salvage therapy options are limited and survival is typically short. Improving early treatments and providing alternative options are crucial for enhancing long-term outcomes. To address this unmet need, various companies are developing regimens such as LUNSUMIO (mosunetuzumab) + POLIVY, Plamotamab + Tafasitamab + Lenalidomide, Zilovertamab vedotin + R-GemOx, and Glofitamab + GemOx (gemcitabine/oxaliplatin).

The promising results from the STARGLO study are the first to demonstrate the potential of a CD20 x CD3 bispecific antibody to improve outcomes in second or later-line DLBCL for patients who are ineligible for transplant and have few options. Glofit-GemOx showed statistically significant and clinically meaningful benefits in overall survival (25.5 months), progression-free survival (13.8 months), and complete response rate (58.5%) compared to R-GemOx in ASCT-ineligible patients with relapsed/refractory DLBCL. 

However, few experts raised questions regarding the inconsistencies observed in the drug’s efficacy in different geographic regions, but, the number of patients in those two regions was simply too small to draw any conclusions, especially the North America subgroup, which only had 25 patients between the two treatment arms. The safety profile of COLUMVI combined with GemOx aligns with the known risks of the individual drugs. This class is expected to be beneficial in the post-CART setting, where treatment options are scarce. Additionally, patients can begin treatment with COLUMVI without delay, which is particularly crucial for those with highly aggressive disease at risk of rapid progression.

Roche plans to submit the STARGLO results to the FDA. If approved, COLUMVI will go toe to toe against CD19 CAR-T therapies, including Bristol Myers Squibb’s BREYANZI and Gilead Sciences’ YESCARTA in second-line DLBCL.

For more insight into the patient's burden/epidemiology, treatment, and changing market landscape-related advancements, refer to the Diffuse Large B-cell Lymphoma - Market Insight, Epidemiology and Market Forecast – 2034 report.