SUMMARY: The FDA on December 22, 2022, granted accelerated approval to LUNSUMIO® (Mosunetuzumab-axgb), a bispecific CD20-directed CD3 T-cell engager for adult patients with Relapsed or Refractory Follicular Lymphoma (FL) after two or more lines of systemic therapy.
The American Cancer Society estimates that in 2022, about 80,470 people were diagnosed with Non Hodgkin Lymphoma (NHL) in the United States and about 20,250 individuals died of this disease. Indolent Non Hodgkin Lymphomas are mature B cell lymphoproliferative disorders and include Follicular Lymphoma, Nodal Marginal Zone Lymphoma (NMZL), Extranodal Marginal Zone Lymphoma (ENMZL) of Mucosa-Associated Lymphoid Tissue (MALT), Splenic Marginal Zone Lymphoma (SMZL), LymphoPlasmacytic Lymphoma (LPL) and Small Lymphocytic Lymphoma (SLL). Follicular Lymphoma is the most indolent form and second most common form of all NHLs and they are a heterogeneous group of lymphoproliferative malignancies. Approximately 22% of all NHLs are Follicular Lymphomas (FL).
Advanced stage indolent NHL is not curable and as such, prolonging Progression Free Survival (PFS) and Overall Survival (OS), while maintaining Quality of Life, have been the goals of treatment intervention. Asymptomatic patients with indolent NHL are generally considered candidates for “watch and wait” approach. Patients with advanced stage symptomatic Follicular Lymphoma are often treated with induction chemoimmunotherapy followed by maintenance RITUXAN® (Rituximab). This can result in a median Progression Free Survival of 6-8 years. However, approximately 30% of the patients will relapse in 3 years, and treatment options are limited for patients with relapses after multiple treatments. Patients with Follicular Lymphomas often experience a relapsing and remitting pattern of disease and may be exposed to multiple lines of therapy over the course of their disease. In spite of the availability of multiple systemic therapies for Follicular Lymphoma, the efficacy of these regimens drops off rapidly with later lines of therapy. Novel therapies are therefore being investigated to improve outcomes.
LUNSUMIO® is a first-in-class CD20 x CD3 T-cell engaging bispecific antibody designed to target CD20 on the surface of B cells and CD3 on the surface of T cells. This dual targeting activates and redirects a patient’s existing T cells to engage and eliminate target B cells by releasing cytotoxic proteins into the B cells.
This FDA approval was based on the positive results from the Phase II GO29781 study, which is a multicenter, open-label, dose-escalation and dose-expansion trial evaluating the safety, efficacy, and pharmacokinetics of LUNSUMIO® in patients with heavily pretreated Follicular Lymphoma, including those who were at high risk of disease progression or whose disease was refractory to prior therapies. The efficacy population consisted of 90 enrolled patients with Relapsed or Refractory FL (Grade 1-3a) who had received at least two prior lines of systemic therapy, including an anti-CD20 monoclonal antibody and an alkylating agent.
LUNSUMIO® was administered IV in 21-day cycles with Cycle 1 step-up dosing of 1 mg on Cycle 1, Day 1, 2 mg on Cycle 1 Day 8, 60 mg on Cycle 1 Day 15, 60 mg on Cycle 2 Day 1, and 30 mg on Day 1 in subsequent cycles. Patients with a Complete Response discontinued therapy after 8 cycles. Patients with a Partial Response or Stable disease continued treatment for up to 17 cycles unless they experienced progressive disease or unacceptable toxicity. The Primary endpoint was Objective Response Rate (ORR) assessed by an Independent Review Committee according to standard criteria for Non-Hodgkins Lymphoma.
The ORR was seen in 80% of patients treated with LUNSUMIO® with 60% achieving Complete Responses. A majority of patients (57%) maintained responses for at least 18 months. With a median follow up of 14.9 months among responders, the estimated median Duration of Response was 22.8 months and the estimated Duration of Response at 12 months and 18 months was 62% and 57%, respectively. Among 218 patients with hematologic malignancies who received LUNSUMIO® at the recommended dose, the most common Adverse Event was Cytokine Release Syndrome (CRS) seen in 39% of patients, which can be severe and life-threatening. The median duration of CRS events was 3 days. Other common Adverse Events included fatigue, rash, fever and headache.
It was concluded from this study that in patients with heavily pretreated Follicular Lymphoma, chemotherapy-free, fixed-duration treatment with LUNSUMIO® induced high rates of Complete Remissions with favorable safety profile, allowing potential administration as an outpatient regimen.
Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. Budde LE, Sehn LH, Matasar M, et al. The Lancet Oncology 2022; 23:1055-1065.