FDA approves Columvi, the first and only bispecific antibody with a fixed-duration treatment for people with relapsed or refractory diffuse large B-cell lymphoma – Roche

Roche announced that the FDA has approved Columvi (glofitamab-gxbm) for the treatment of adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) not otherwise specified or large B-cell lymphoma (LBCL) arising from follicular lymphoma, after two or more lines of systemic therapy.

This indication is approved under accelerated approval based on response rate and durability of response in the phase I/II NP30179 study. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Columvi will be available in the US in the coming weeks.

“People with diffuse large B-cell lymphoma who have gone through multiple lines of therapy have a poor prognosis and desperately need additional treatment options,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “As an off-the-shelf, fixed-duration treatment providing durable response rates, we believe Columvi could change the way this aggressive lymphoma is treated, reinforcing our dedication to bringing innovative treatment options to people with critical unmet needs.”

DLBCL is an aggressive, hard-to-treat disease and is the most common form of non-Hodgkin lymphoma in the US. While many people with DLBCL are responsive to treatment, the majority of those who relapse or are refractory to subsequent treatments have poor outcomes.

“Patients with relapsed or refractory diffuse large B-cell lymphoma may experience rapid progression of their cancer and often urgently need an effective treatment option that can be administered without delay,” said Krish Patel, M.D., Director of the Lymphoma Program at the Swedish Cancer Institute in Seattle and investigator of the Columvi phase I/II NP30179 study. “Experience from clinical trials demonstrates that Columvi can provide patients with relapsed or refractory diffuse large B-cell lymphoma a chance for complete remission with a fixed duration immunotherapy and that such remissions can potentially be sustained after the end of their treatment.”

The FDA accelerated approval is based on positive results from the phase I/II NP30179 study of Columvi given as a fixed course for 8.5 months in 132 patients with DLBCL who had relapsed or were refractory to prior therapies, including about one-third (30%) who had received prior CAR T-cell therapy. Additionally, 83% were refractory to their most recent therapy. Results showed patients treated with fixed-duration Columvi achieved durable remission, with 56% of patients achieving an overall response (OR; 74/132 [95% confidence interval (CI): 47-65]) and 43% of patients achieving a complete response (CR; 57/132 [95% CI: 35-52]). Over two-thirds of those who responded continued to respond for at least nine months (68.5% [95% CI: 56.7-80.3]). The OR rate is the combination of CR rate (a disappearance of all signs and symptoms of cancer) and partial response rate (a decrease in the amount of cancer in the body). The median duration of response was 1.5 years (18.4 months [95% CI: 11.4-not estimable]). Data from the NP30179 study were recently published in the New England Journal of Medicine.

Among 145 patients who received Columvi in the study, the most common adverse events (AEs) were cytokine release syndrome (CRS; 70%), which may be serious or life-threatening, musculoskeletal pain (21%), fatigue (20%) and rash (20%). CRS was generally low grade (52% experienced Grade 1, and 14% experienced Grade 2).

Columvi is the first and only CD20xCD3 T-cell engaging bispecific antibody for the treatment of R/R DLBCL that is given for a defined period of time, unlike treat-to-progression approaches where treatment is given indefinitely until the cancer progresses or the therapy cannot be tolerated, whichever occurs first. Designed to be completed in approximately 8.5 months, Columvi offers people with R/R DLBCL a target end date for their course of treatment and the possibility of a treatment-free period. Additionally, Columvi is a chemotherapy-free treatment option that is off-the-shelf and ready for infusion.

Columvi is part of Roche’s broad and industry-leading CD20xCD3 T-cell-engaging bispecific antibody clinical development programme. This includes the phase III STARGLO study evaluating Columvi in combination with gemcitabine and oxaliplatin (GemOx) versus MabThera/Rituxan (rituximab) in combination with GemOx in patients with DLBCL who have been treated with one or more previous therapies and are ineligible for autologous stem cell transplant. Roche’s haematology bispecific antibody portfolio also includes Lunsumio (mosunetuzumab), which was granted accelerated approval by the FDA in December 2022 for the treatment of adult patients with R/R follicular lymphoma (FL) after two or more lines of systemic therapy. Roche is exploring the potential of both Columvi and Lunsumio as monotherapies and in combination with other therapies, including Polivy (polatuzumab vedotin), in earlier lines of treatment with the goal of providing patients with long-lasting outcomes. This robust development programme includes two phase III studies: CELESTIMO, investigating Lunsumio plus lenalidomide in second line plus (2L+) FL, and SUNMO, investigating Lunsumio plus Polivy in 2L+ DLBCL. Columvi received its first worldwide approval in Canada, and the European Medicines Agency’s Committee for Medicinal Products for Human Use recently granted a positive opinion recommending its approval.

See-“Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma” -Michael J. Dickinson et al.NEJM December 11, 2022 DOI: 10.1056/NEJMoa2206913.