Roche's Columvi boosts lymphoma survival for earlier use

Roche recently presented updated, longer-term overall survival (OS) data from the Phase III STARGLO trial, highlighting a statistically significant and clinically meaningful survival benefit for their CD20xCD3 bispecific antibody Columvi (glofitamab) in patients with earlier-line relapsed or refractory diffuse large B-cell lymphoma (DLBCL). These results were disclosed at the European Hematology Association (EHA) annual meeting, providing further insights into the top-line findings initially reported in April. At that time, it was revealed that Columvi, in combination with chemotherapy, achieved the trial's primary endpoint of improved overall survival compared to the Rituxan/MabThera (rituximab) and chemotherapy combination. These findings support Roche’s efforts to expand the drug’s application to earlier-line treatment settings.

The competition among bispecific antibodies is intense. Last year, regulators in the US, Europe, and Canada granted early approval to Columvi for third-line treatment of DLBCL patients based on response-rate data from a Phase I/II trial. The STARGLO trial results are crucial for Roche as it aims to distinguish Columvi from competing drugs such as AbbVie/Genmab's Epkinly (epcoritamab), another drug in the same class that has also received authorization for third-line DLBCL treatment. Meanwhile, Regeneron is striving to enter the market with its CD20xCD3 bispecific antibody, odronextamab. However, the FDA has demanded more extensive confirmatory studies, rejecting earlier filings for the drug in third-line relapsed/refractory follicular lymphoma and DLBCL.

The STARGLO trial involved 274 participants with relapsed or refractory DLBCL who had undergone at least one prior line of therapy and were ineligible for autologous stem cell transplant. Participants were randomized to receive either Columvi or Rituxan/MabThera, both in combination with gemcitabine and oxaliplatin. Approximately two-thirds of the participants had only one prior treatment, while the rest had undergone at least two previous therapies.

As of the primary analysis cutoff in March 2023, Columvi showed a 41% improvement in overall survival compared to the comparator arm. There was also a significant 63% enhancement in progression-free survival (PFS), with complete response (CR) rates of 50.3% for the Columvi arm versus 22% for the Rituxan/MabThera arm. The follow-up analysis cutoff on February 16 confirmed these positive trends, with Columvi continuing to demonstrate a superior median OS of 25.5 months compared to 12.9 months for the comparator. This translated to an overall survival benefit of 38% in favor of Columvi. Additionally, Columvi outperformed Rituxan/MabThera in PFS, with a benefit of 60% (13.8 vs. 3.6 months), and in CR rate (58.5% vs. 25.3%).

Researchers emphasized that Columvi is the first CD20xCD3 bispecific antibody to show a survival benefit in DLBCL in a randomized Phase III trial. However, the Columvi combination was associated with a higher incidence of adverse events (AEs) compared to the Rituxan regimen. Nearly 70% of Columvi patients experienced Grade 3 or 4 side effects, compared to 36% in the Rituxan arm. Additionally, around 8% of Columvi patients died during the study, compared to 4.5% with Rituxan, primarily due to more COVID-19-related adverse events. Researchers noted that when adjusting for greater exposure, the adverse event rates were similar between the two treatment arms.