Source – Roche
On 11 July 2023 Roche announced that the European Commission (EC) has given conditional approval for Columvi (glofitamab) as a treatment for adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who have undergone two or more lines of systemic therapy. This approval makes Columvi the first CD20xCD3 T-cell-engaging bispecific antibody available in Europe for treating the most common and aggressive form of lymphoma in patients who have received multiple lines of therapy. Columvi has the potential to revolutionize the current standard of care for DLBCL. Not only does it produce early and long-lasting responses in heavily pre-treated or refractory DLBCL patients, but it also offers a fixed treatment duration, providing patients with a clear endpoint and the possibility of a treatment-free period. Furthermore, Columvi is a chemotherapy-free treatment option that is readily available, eliminating the need for cell collection and genetic engineering, which can be a time-consuming process before commencing treatment. This is particularly advantageous for high-risk patients whose disease progression needs to be addressed promptly.
DLBCL is a rapidly progressive type of lymphoma and one of the most prevalent forms of blood cancer among adults in Europe, with approximately 36,000 new cases diagnosed each year. Although many DLBCL patients respond well to initial treatment, four out of ten individuals are not cured with the current frontline therapy, and those who require subsequent lines of treatment often have poor outcomes.
“As pioneers in the development of innovative T-cell-engaging bispecific antibodies, we are delighted that we can now offer Columvi as the first approved treatment of its kind to people in Europe. We are confident that thanks to its off-the-shelf availability, fixed-duration regimen and durability, Columvi will positively transform the treatment experience for relapsed or refractory diffuse large B-cell lymphoma.”
– Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development
“As the lead investigator for the NP30179 study, I have seen first-hand the early and long-lasting responses that Columvi can induce, when given to patients for a fixed period of time. It is exciting that with this approval, patients in Europe with heavily pre-treated or refractory diffuse large B-cell lymphoma will now have a new, potentially practice-changing treatment option that will allow them time off of therapy to resume their routine activities, helping to alleviate some of the physical and emotional burdens caused by cancer treatment.”
– Michael Dickinson, M.D., Ph.D., principal study investigator and Associate Professor, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Australia
The approval of Columvi is based on positive results from a pivotal cohort of the Phase I/II NP30179 study, where a fixed course of Columvi induced early and long-lasting responses in patients with R/R DLBCL. Among the patients, 83.3% were refractory to their most recent therapy, 90% were refractory to any previous therapy, and approximately one-third (35.2%) had previously received CAR T-cell therapy. The results demonstrated that Columvi, when administered for a fixed duration, led to a complete response (the disappearance of all signs of cancer) in 35.2% (n=38/108) of patients, while 50% (n=54/108) achieved an overall response (a combination of complete and partial response). Among those who achieved a complete response, 74.6% (95% CI: 59.19-89.93) maintained the response at 12 months, and the median duration of the complete response was not reached. The median follow-up for the duration of response was 12.8 months, and the median time to the first complete response was 42 days (95% CI: 41-47). The most common adverse events reported were cytokine release syndrome (CRS; 64.3%), neutropenia (a reduction in white blood cells [37.7%]), anemia (30.5%), and thrombocytopenia (low blood platelet count [24.7%]). CRS was generally of low grade (Grade 1: 48.1%; Grade 2: 12.3%). Only one patient discontinued treatment due to CRS.
Additional data from a larger cohort in the NP30179 study, published in the New England Journal of Medicine, further support the efficacy of Columvi. Fixed-duration treatment with Columvi resulted in early and sustained responses in heavily pre-treated or refractory DLBCL patients, with 39.4% (n=61/155) achieving a complete response and a median duration of response of 18.4 months. The median time to a complete response was 42 days (95% CI: 42-44), with most responses observed at the first scheduled response assessment (around 1.4 months after treatment initiation). Additionally, half of the patients (51.6%; n=80/155) achieved an overall response. The most common adverse event observed was CRS, which was generally of low grade (Grade 1: 47.4%; Grade 2: 11.7%) and predominantly occurred at the initial doses. Treatment discontinuation due to Columvi-related adverse events occurred in 3.2% of patients.
The US Food and Drug Administration (FDA) recently approved Columvi for the treatment of adult patients with R/R DLBCL not otherwise specified or large B-cell lymphoma (LBCL) arising from follicular lymphoma (FL) after two or more lines of systemic therapy. Columvi is also approved in Canada for the treatment of adult patients with R/R DLBCL not otherwise specified, DLBCL arising from follicular lymphoma (FL), or primary mediastinal B-cell lymphoma who have received two or more lines of systemic therapy and are ineligible for or cannot receive CAR T-cell therapy, or have previously received CAR T-cell therapy. Submissions to other health authorities worldwide are currently underway.
Roche continues to advance Columvi’s clinical development program, which includes the Phase III STARGLO trial. This trial evaluates the combination of Columvi with gemcitabine and oxaliplatin (GemOx) compared to rituximab in combination with GemOx for patients with second-line or later DLBCL who are not eligible for autologous stem cell transplant. Additional Phase III studies are also planned, including those investigating the use of Columvi in first-line DLBCL in combination with other novel chemotherapy-free agents like Polivy (polatuzumab vedotin), with the goal of providing patients with long-lasting treatment outcomes.
Roche remains committed to leveraging its extensive expertise in hematology to explore innovative solutions that redefine treatment standards and improve upon existing care protocols for the benefit of patients. Through its comprehensive clinical development program for CD20xCD3 T-cell-engaging bispecific antibodies, Roche is investigating the potential of both Columvi and Lunsumio (mosunetuzumab) in earlier lines of treatment and in combination with other novel and chemotherapy-free agents such as Polivy (polatuzumab vedotin), with the aim of delivering lasting positive outcomes for patients.