On December 22, Genentech’s bispecific monoclonal antibody Lunsumio (mosunetuzumab) was approved by the FDA for use in adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) after two or more lines of systemic therapy. Accelerated approval was granted based on positive results from the pivotal Phase I/II GO29781 (NCT02500407) trial in which Lunsumio was investigated as a single agent and in combination with Roche’s Tecentriq (atezolizumab) in this FL patient subgroup.

FL is a hematological cancer in which B lymphocytes (B cells) become cancerous and accumulate in ‘follicles’ in the lymph nodes. It is the most common subtype of indolent non-Hodgkin’s lymphoma (NHL) and constitutes approximately one in five cases of NHL. Most FL patients can achieve a durable complete or partial response after front-line induction chemoimmunotherapy. However, the cure rate for FL remains low, and most patients who relapse have poor overall survival (OS) rates. Therefore, developing therapies with novel mechanisms of action (MOAs) for this patient subgroup remains a critical unmet need. Lunsumio is a first-in-class bispecific antibody that exhibits dual targeting of both B cell antigen CD20 and CD3 of T-cell receptors. By forming a synapse between the T cell and the tumour cell, this upregulates the production of cytolytic proteins and cell adhesion molecules, eventually leading to the lysis of CD20-presenting B cells.

In the single-arm GO29781 trial, objective response rate (ORR) was examined in 90 patients with R/R FL who had been treated with two prior lines of systemic therapy, including an anti-CD20 monoclonal antibody and an alkylating agent. The trial yielded positive results with an ORR of 80% and 57% of patients maintaining responses for at least 18 months. A median duration of response (DOR) of 22.8 months and a complete response of 60% was also observed in these patients. In the pooled safety population of 218 patients, which included patients with R/R NHL and chronic lymphocytic leukemia (CLL) who received Lunsumio at the recommended dose, cytokine release syndrome (CRS) and neurological toxicity occurred in 39% of patients. At the 64th American Society of Hematology (ASH) Annual Meeting and Exposition, on December 10–13, grade 3/4 and serious adverse events were reported in 49% and 45% of patients in this trial, respectively.

Following the results of the dose-escalation study, the FDA recommends eight cycles of Lunsumio monotherapy. With a fixed course of eight cycles of therapy potentially costing patients more than $150,000 over the course of treatment, Genentech is expected to generate significant revenue. Lunsumio is expected to compete with Gilead’s autologous chimeric antigen receptor (CAR) T-cell therapy Yescarta (axicabtagene ciloleucel) to be the market leader in later-line therapy for R/R FL, given that Lunsumio has the advantage of being an off-the-shelf therapy. According to GlobalData’s consensus analyst forecasts, Lunsumio’s global sales in this indication are expected to reach $900m by 2028, while Yescarta is projected to reach $2.3bn in global sales across two indications: FL and diffuse large B-cell lymphoma (DLBCL), with a heavier weighting toward the latter indication.