The World's First CD20/CD3 Double Antibody Was Approved for Marketing

On June 8, Roche announced that the European Commission has granted a conditional marketing authorization for the CD20xCD3 T cell-binding bispecific antibody Lunsumio (mosunetuzumab) for the treatment of patients with relapsed or refractory (R) disease who have received at least two prior systemic therapies. /R) Adult patients with follicular lymphoma (FL).

Lunsumio is a first-in-class CD20xCD3 T cell engaging bispecific antibody designed to target CD20 on the surface of B cells and CD3 on the surface of T cells, activating and redirecting a patient's existing endogenous T cells through dual targeting, Malignant B cells are eliminated by releasing cytotoxic proteins into B cells. Lunsumio is still being developed as a monotherapy or in combination with other drugs for the treatment of patients with B-cell non-Hodgkin lymphoma, including follicular lymphoma, diffuse large B-cell lymphoma and other blood cancers.

Lunsumio has previously been granted Breakthrough Drug Designation (BTD) by the FDA, and the EMA Committee for Medicinal Products for Human Use (CHMP) also issued a positive opinion in April this year, recommending the approval of mosunetuzumab.

The approval is based on the GO29781 study, a Phase I/II multicenter, open-label, dose-escalation and expansion study to evaluate the safety of Lunsumio (mosunetuzumab) in relapsed or refractory B-cell non-Hodgkin patients , efficacy and pharmacokinetic characteristics. Primary endpoints included complete response rate (best response) as determined by an independent review agency and secondary endpoints of objective response rate, duration of response, progression-free survival, safety and tolerability.

Results presented for the first time at the 2021 American Society of Hematology Annual Meeting (ASH) & Exposition show that Lunsumio induced high rates of complete responses in FL patients with multiple prior treatments, with most complete responses lasting at least 18 months, and is well tolerated. After a median follow-up of 18.3 months, responders had a median duration of response of 22.8 months (95% CI: 9.7 - not estimable), a complete response rate of 60% (n=54/90), and an objective response rate of 80 % (n=72/90).

The most common adverse event was cytokine release syndrome (39%), which was usually low-grade (Grade 2: 14%) and resolved at the end of treatment. Other common (≥20%) AEs mainly included neutropenia, pyrexia, hypophosphatemia, and headache.

Follicular lymphoma (FL) is the most common indolent (slow-growing) form of non-Hodgkin lymphoma (NHL), accounting for about one in five cases of NHL. It is estimated that more than 100,000 people worldwide are diagnosed with FL each year, including more than 28,000 in Europe.

Lunsumio is currently conducting a phase III study of combined lenalidomide versus rituximab combined with lenalidomide in patients with relapsed or refractory follicular lymphoma receiving ≥1 line of systemic therapy (CELESTIMO), As well as the efficacy study of combined Polivy (CD79b antibody conjugated drug) in the treatment of diffuse large B-cell lymphoma (DLBCL).

In addition to Lunsumio, Roche is also developing another CD20xCD3 bispecific antibody, glofitamab, which is also in Phase III clinical studies. Recently, data presented at the ASCO 2022 meeting again showed that glofitamab induced high and durable complete response rates in heavily pretreated patients with diffuse large B-cell lymphoma.