FDA Accepts Genentech’s Columvi Combination Application for Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Genentech, a part of the Roche Group, has announced that the U.S. Food and Drug Administration (FDA) has accepted its supplemental Biologics License Application (sBLA) for Columvi® (glofitamab-gxbm) combined with gemcitabine and oxaliplatin (GemOx) for treating individuals with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who have undergone at least one prior therapy and are not suitable for autologous stem cell transplant. The FDA's decision on this application is anticipated by July 20, 2025.

Historically, high-dose chemotherapy followed by stem-cell transplant has been the standard second-line therapy for patients with R/R DLBCL. However, not all patients qualify due to age or other health conditions. Despite the introduction of newer treatments, many patients still face challenges, underscoring the need for alternative options to enhance survival outcomes.

"For patients with aggressive lymphomas like DLBCL, timely and effective therapies are crucial to mitigate disease progression and improve long-term outcomes," stated Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development. He expressed optimism about the survival benefits observed with the Columvi combination and its potential to serve as a significant treatment option for patients requiring alternative therapies.

The sBLA submission is supported by results from the Phase III STARGLO study, which were presented at the European Hematology Association Congress and published in The Lancet. The study demonstrated that Columvi combined with GemOx significantly improved overall survival (OS) compared to Rituxan® (rituximab) combined with GemOx (R-GemOx), marking it as the first CD20xCD3 bispecific antibody to show a survival benefit in DLBCL in a randomized Phase III trial. The safety profile of the combination was consistent with the known safety profiles of the individual drugs.

In addition to the FDA, the data from the STARGLO study have been submitted to other global health authorities, including the European Medicines Agency, for approval consideration.

Columvi is a key component of Genentech’s leading CD20xCD3 bispecific antibody program, which has treated over 3,000 patients in clinical trials and more than 2,600 patients in clinical practice. Columvi was the first fixed-duration bispecific antibody to receive accelerated approval by the U.S. FDA and conditional marketing authorization in the EU for monotherapy in people with R/R DLBCL after two or more lines of systemic therapy. It is currently approved in over 50 countries worldwide.

Genentech is also investigating Columvi in combination with Polivy® (polatuzumab vedotin-piiq), Rituxan, cyclophosphamide, doxorubicin, and prednisone (R-CHP) for previously untreated DLBCL in the Phase III SKYGLO study, as part of efforts to improve treatment standards in earlier stages of DLBCL and prevent relapse.

The Phase III STARGLO study is a multicenter, open-label, randomized trial evaluating the efficacy and safety of Columvi in combination with GemOx versus Rituxan plus GemOx in patients with R/R DLBCL who have received at least one prior therapy and are not candidates for autologous stem cell transplant or have received two or more prior therapies. Preclinical research suggested an enhanced antitumor effect when combining Columvi with GemOx versus GemOx alone, prompting the initiation of the STARGLO study to explore this further. The primary endpoint is overall survival, with secondary endpoints including progression-free survival, complete response rate, objective response rate, duration of objective response, and safety and tolerability.

In the primary analysis, conducted after a median follow-up of 11.3 months, patients treated with Columvi plus GemOx exhibited a significantly longer survival, with a 41% reduction in the risk of death compared to those treated with R-GemOx. Median OS was not reached with the Columvi combination versus nine months for R-GemOx. The safety profile of the combination was aligned with the known safety profiles of the individual drugs, with the most common adverse event being cytokine release syndrome, which was generally low grade and occurred mainly in Cycle 1.

The STARGLO study aims to confirm the accelerated approval of Columvi in the U.S. and conditional marketing authorization in the EU for people with R/R DLBCL after two or more lines of systemic therapy, based on previous Phase I/II study results.

Columvi is a CD20xCD3 T-cell engaging bispecific antibody targeting CD3 on T cells and CD20 on B cells. Designed with a novel 2:1 structural format, it brings T cells into close proximity with B cells, activating the release of cancer cell-killing proteins. Columvi is part of Genentech’s extensive CD20xCD3 bispecific antibody program, which also includes Lunsumio® (mosunetuzumab), aiming to provide personalized treatment options for people with blood cancers.