FDA Accepts Roche’s Supplemental Biologics License Application of Columvi for Relapsed or Refractory Diffuse Large B-Cell Lymphoma

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The FDA has accepted Roche’s supplemental Biologics License Application (sBLA) for Columvi (glofitamab) in combination with gemcitabine and oxaliplatin (GemOx) for treating relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) in patients who are ineligible for autologous stem cell transplant after at least one prior line of therapy. According to the company, the sBLA is supported by the Phase III STARGLO trial, which demonstrated a statistically significant and clinically meaningful overall survival (OS) improvement with the Columvi-GemOx combination compared to Rituxan (rituximab)-GemOx. This finding makes Columvi the first CD20xCD3 bispecific antibody to show a survival benefit in DLBCL in a randomized Phase III trial, according to Roche.¹

“For people with aggressive lymphomas like DLBCL, timely intervention with effective therapies can be crucial to reduce the risk of disease progression and improve long-term outcomes,” said Levi Garraway, MD, PhD, chief medical officer, head, global product development, Roche, in a press release. “We are encouraged by the overall survival benefit seen with this Columvi combination and hope it can become an important treatment option for those who are in need of alternative therapies.”

The multicenter, open-label, randomized STARGLO trial evaluated the efficacy and safety of Columvi in combination with GemOx versus MabThera/Rituxan in combination with GemOx (R-GemOx). According to preclinical research, there was an increased antitumor effect when combining Columvi with GemOx over GemOx alone. The primary endpoint of the study was OS, with secondary endpoints that included progression-free survival, complete response rate, objective response rate, duration of objective response, safety, and tolerability.

Results found that patients treated with Columvi plus GemOx lived significantly longer, with a 41% reduction in the risk of death. However, median OS was not reached with the Columvi regimen versus nine months for R-GemOx.

The rate of adverse events (AEs) were higher with the Columvi combination versus R-GemOx, with investigators noting a higher median number of cycles received with the Columvi combination. One of the most commonly reported AEs was cytokine release syndrome, which was generally low grade. The safety profile found that the treatment was consistent with the individual components.¹

According to PubMed, DLBCL accounts for one-third of all non-Hodgkin lymphomas, ranging between 20% and 50% by country. DLBCL incidence rises with age and is generally higher in males than females. Additionally, incidence is highest among non-Hispanic whites in the United States. While the incidence of DLBCL rose dramatically in the first half of the 20th century, it has largely plateaued since then. Family history in cancer and multiple genetic susceptibility loci have been found to be well-established risk factors for DLBCL. Lastly, there is strong evidence for multiple environmental exposures in DLBCL etiology, including exposure to trichloroethylene, benzene, and pesticides and herbicides, with recent associations noted with glyphosate.²

According to the Lymphoma Research Foundation, more than 18,000 people in the United States are diagnosed with DLBCL each year. Most patients are over 60 years of age when first diagnosed, but it can also occur during childhood in rare cases.³

Currently, Roche’s efforts to advance CD20xCD3 bispecific antibody therapies include over 3,000 patients in clinical trials, with Columvi previously approved as a monotherapy for R/R DLBCL in over 50 countries. Additional studies, such as the Phase III SKYGLO trial, are underway to explore its use in earlier DLBCL treatment settings. Roche stated that data from the STARGLO trial have been submitted to other health authorities around the world for approval consideration, including the European Medicines Agency.¹

References

1. FDA accepts supplemental Biologics License Application for Roche’s Columvi combination for people with relapsed or refractory diffuse large B-cell lymphoma. Roche. December 5, 2024. Accessed December 5, 2024. https://www.roche.com/media/releases/med-cor-2024-12-05

2. Epidemiology and etiology of diffuse large B-cell lymphoma. NIH. Accessed December 5, 2024. https://pubmed.ncbi.nlm.nih.gov/38242772/#:~:text=As%20the%20most%20common%20non,syndromes%2C%20and%20organ%20transplant%20recipients.

3. Diffuse Large B-Cell Lymphoma. LRF. Accessed December 5, 2024. https://lymphoma.org/understanding-lymphoma/aboutlymphoma/nhl/dlbcl/#:~:text=Diffuse%20large%20B%2Dcell%20lymphoma%20(DLBCL)%20is%20the%20most,part%20of%20the%20lymphatic%20system.