Roche has announced that their supplemental Biologics License Application (sBLA) for Columvi (glofitamab), when used in combination with gemcitabine and oxaliplatin (GemOx), has been accepted by the US Food and Drug Administration (FDA). This combination is intended for patients suffering from relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who have undergone at least one previous line of treatment and are not eligible for an autologous stem cell transplant. The FDA is anticipated to reach a decision regarding approval by July 20, 2025.
Traditionally, the standard second-line therapy for those with R/R DLBCL has involved high-dose chemotherapy followed by a stem-cell transplant. However, some patients are not suitable candidates due to their age or existing medical conditions. Despite emerging therapies, numerous patients face obstacles in obtaining treatment, necessitating alternative solutions to enhance survival rates.
“For those battling aggressive lymphomas such as DLBCL, initiating effective therapies promptly is vital to curtail disease progression and improve long-term survival,” stated Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development. “We are optimistic about the survival benefits observed with the Columvi combination and hope it offers a key treatment option for those seeking alternative therapies.”
The sBLA is supported by findings from the Phase III STARGLO study, presented at this year’s European Haematology Association Congress and published in The Lancet. The research demonstrated that Columvi, alongside GemOx, provided a statistically significant and clinically relevant improvement in overall survival (OS) compared to MabThera/Rituxan (rituximab) in tandem with GemOx (R-GemOx). Columvi emerged as the first CD20xCD3 bispecific antibody to yield survival advantages in DLBCL in a randomized Phase III trial. The safety profile of the combination aligns with those of the individual drugs.
Results from the STARGLO study have been shared with various global health authorities, including the European Medicines Agency, for consideration.
Columvi is part of Roche’s leading CD20xCD3 bispecific antibody initiative, which has seen clinical trials involving over 3,000 patients and more than 2,600 treated in practice. Columvi was the pioneering fixed-duration bispecific antibody to gain accelerated approval from the US FDA and conditional marketing authorization in the EU for monotherapy in R/R DLBCL post-two or more systemic therapy lines, and it is presently approved in over 50 countries.
In pursuit of elevating treatment standards for early-stage DLBCL, where long-term outcomes can be impacted and relapse avoided, Columvi is also under investigation combined with Polivy (polatuzumab vedotin), MabThera/Rituxan, cyclophosphamide, doxorubicin, and prednisone (R-CHP) for previously untreated DLBCL in the Phase III SKYGLO study.
The STARGLO study [GO41944; NCT04408638], a Phase III, open-label, multicenter trial, assesses the efficacy and safety of Columvi (glofitamab) combined with GemOx versus R-GemOx in patients with relapsed or refractory diffuse large B-cell lymphoma, who have had at least one prior treatment line and are not viable candidates for stem cell transplants, or who have had multiple prior treatments. Initial research suggested increased anti-tumor effectiveness of Columvi plus GemOx over GemOx alone, prompting the STARGLO study to further examine this combination’s potential benefits. Outcomes measured encompass overall survival (OS; primary endpoint), progression-free survival, complete response rate, objective response rate, duration of response (secondary endpoints), and safety and tolerability.
In the primary analysis following a median follow-up of 11.3 months, patients receiving Columvi plus GemOx experienced significantly prolonged survival, showcasing a 41% decline in death risk (HR=0.59, 95% CI: 0.40-0.89, p=0.011) versus R-GemOx. The median OS wasn’t reached with Columvi, while it was 9 months for R-GemOx. The safety profile mirrored the known aspects of individual medicines. Adverse event incidence was higher with Columvi than with R-GemOx, corresponding to a greater median number of cycles received (11 versus 4). Cytokine release syndrome was a notable adverse event, generally low-grade (Any Grade: 44.2%, Grade 1: 31.4%, Grade 2: 10.5%, Grade 3: 2.3%) and mostly occurring in Cycle 1.
STARGLO will confirm the FDA’s accelerated approval of Columvi and the EU’s conditional marketing authorization for individuals with R/R DLBCL after multiple therapy lines based on the pivotal Phase I/II NP30179 study [NCT03075696].
Columvi acts as a CD20xCD3 T-cell engaging bispecific antibody, targeting CD3 on T-cells and CD20 on B-cells. Its innovative 2:1 structural format allows one region to bind to CD3 on T-cells, an immune cell type, and two regions to attach to CD20 on B-cells, whether healthy or cancerous. This dual-targeting draws the T-cell near the B-cell, triggering the release of cancer-destroying proteins from the T-cell. Columvi is part of Roche’s expansive CD20xCD3 bispecific antibody development initiative, which includes Lunsumio (mosunetuzumab), aimed at delivering tailored treatments for various blood cancers and healthcare systems.
Investigations are ongoing with Columvi as a standalone therapy and in conjunction with other medications for diffuse large B-cell and mantle cell lymphomas.
DLBCL is the most prevalent type of non-Hodgkin lymphoma (NHL), representing approximately one-third of all NHL cases.6 This aggressive form of NHL usually responds to initial treatment, but 40% of individuals may experience relapsed or resistant disease, at which stage treatment options are limited, and life expectancy is reduced. Enhancing therapies at earlier disease stages and offering alternative options can positively impact long-term outcomes. Each year, about 160,000 individuals are diagnosed with DLBCL globally.
Roche has been at the forefront of developing medications for both malignant and non-malignant blood diseases for over a quarter of a century, harnessing extensive experience and knowledge in this therapeutic field. Presently, Roche invests more comprehensively than ever in delivering innovative solutions to patients across a range of hematological conditions. Roche’s medicines include MabThera/Rituxan (rituximab), Gazyva/Gazyvaro (obinutuzumab), Polivy (polatuzumab vedotin), in collaboration with AbbVie, Hemlibra (emicizumab), PiaSky (crovalimab), Lunsumio (mosunetuzumab), and Columvi (glofitamab). Our investigational hematology medicines pipeline includes T-cell engaging bispecific antibody cevostamab, which targets FcRH5 and CD3, and Tecentriq (atezolizumab), presenting unique opportunities for combination regimens that aim to enhance patients’ quality of life substantially further.