Roche Presents Promising Phase I/Ib Data for CD20xCD3 Bispecific Antibodies Mosunetuzumab and Glofitamab in Lymphomas with Complete Response Rates of 50–80%

December 09, 2020 /BioValleyBIOON/ -- Roche recently announced new data on two investigational T-cell-engaging CD20xCD3 bispecific antibodies, mosunetuzumab and glofitamab, at the 62nd Annual Meeting of the American Society of Hematology (ASH). The results demonstrated encouraging activity of these two antibody drugs in various types of hematologic cancers.The complete remission rate is 50-80%.

Mosunetuzumab and glofitamab (formerly known as CD20-TCB) are both CD20xCD3 bispecific antibodies that function by simultaneously binding to two distinct targets on two different cell types: CD20 on the surface of malignant B cells and CD3 on the surface of T cells. This dual-targeting mechanism activates and redirects the patient’s existing endogenous T cells to engage with and eliminate these malignant B cells by releasing cytotoxic proteins into the target B cells. This dual-targeting therapy offers an innovative treatment approach for hematologic malignancies, including non-Hodgkin lymphoma (NHL) and multiple myeloma (MM).

To date, inClinical TrialsAmong them, Roche’s two CD20xCD3 T-cell-engaging bispecific antibodies, mosunetuzumab and glofitamab, have demonstrated favorable responses in various types of non-Hodgkin lymphoma (NHL), including relapsed or refractory (R/R) follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL).

The latest results from the Phase I/Ib GO29781 study in patients with relapsed/refractory (R/R) follicular lymphoma (FL) further corroborate this finding. The study demonstrated thatAmong patients with relapsed/refractory follicular lymphoma (R/R FL) treated with mosunetuzumab, 51.6% (n=32/62) achieved complete response (CR).Glofitamab treatment also continues to demonstrate high response rates. For example, new data from the Phase I/Ib NP30179 study in patients with relapsed/refractory non-Hodgkin lymphoma (R/R NHL) show that,Among patients with aggressive relapsed/refractory non-Hodgkin lymphoma (R/R NHL) treated with glofitamab, 53.6% (n=15/28) achieved complete response (CR).In addition, the two bispecific antibodies demonstrated a manageable safety profile. One of the most commonly observed adverse events (AEs) was cytokine release syndrome (CRS), which involves excessive activation of immune cells and is associated with the activation of the humanAutoimmunityKnown Risks of Systemic Immunotherapy. According to current research, cytokine release syndrome (CRS) events associated with mosunetuzumab and glofitamab treatment are predominantly low-grade (mainly Grades 1–2), occur during early treatment cycles, and are largely reversible.

In addition to relapsed/refractory (R/R) disease, mosunetuzumab and glofitamab are also being investigated in earlier lines of therapy, including first-line diffuse large B-cell lymphoma (1L-DLBCL). Preliminary data from the Phase I/II GO40554 study indicate that, in elderly or medically unfit patients with DLBCL who are unable to tolerate full-dose immunochemotherapy,The complete remission (CR) rate of mosunetuzumab monotherapy as first-line treatment for DLBCL was 45.5% (n=10/22).Furthermore, data from the Phase Ib/II GO40515 study showed thatThe complete response rate (CR) of mosunetuzumab combined with chemotherapy as first-line treatment for DLBCL was 79.4% (n=27/34).These are the first bispecific antibody studies to report data in frontline DLBCL; although still early, these results support the potential of mosunetuzumab to provide a new, acute treatment option for these patients.

Mosunetuzumab and glofitamab differ structurally. Mosunetuzumab resembles a natural human antibody but contains two Fab regions, one targeting CD20 and the other targeting CD3. Glofitamab features a novel “2:1” structural configuration, with two Fab regions targeting CD20 and one Fab region binding to CD3. This July, the United StatesFDAMosunetuzumab was granted Breakthrough Therapy Designation (BTD) for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) who have received at least two prior systemic therapies.

These two antibodies are part of Roche’s exploration of several bispecific antibody format strategies to determine the regimens that offer maximal potential clinical benefit for patients. Currently, Roche is advancing robust clinical programs to develop mosunetuzumab and glofitamab as monotherapies and in combination with other agents, as well as more convenient administration routes (e.g., subcutaneous injection), for the treatment of CD20-positive B-cell non-Hodgkin lymphoma (B-NHL), including diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). The company plans to initiate multiple Phase 3 trials in the near future.Clinical Trial. (Bioon.com)

Original Source: Roche presents new data from its bispecific antibody portfolio across a range of blood cancers