Roche Announces Strong Clinical Data for Bispecific Antibodies Mosunetuzumab, Glofitamab, and Cevostamab

December 19, 2021 /BioValleyBIOON/ -- Roche's Genentech recently announcedBispecific antibodies mosunetuzumab (CD20xCD3), glofitamab (CD20xCD3), cevostamab (FcRH5xCD3)Key clinical data. The results continue to show that the three bispecific antibodiesClinical TrialThe efficacy observed is encouraging, and the safety profile is favorable. Currently, Roche is continuing to evaluate these bispecific antibodies in an extensive and comprehensive clinical program, both as monotherapy and in combination with approved and/or novel therapies, aiming to provide tailored treatment options for patients with malignant hematological conditions.

Mosunetuzumab and glofitamab (formerly known as CD20-TCB) are both CD20xCD3 bispecific antibodies., which can simultaneously bind to CD20 on the surface of malignant B cells and CD3 on the surface of T cells, bringing T cells close to tumor cells and eliminating them.TumorCells. Mosunetuzumab and glofitamab differ in structure; mosunetuzumab is similar to natural human antibodies but contains two Fab regions, one targeting CD20 and the other targeting CD3. Glofitamab features a novel "2:1" structural pattern with two Fab regions targeting CD20 and one Fab region targeting CD3. This dual-targeting action activates and redirects the patient’s existing endogenous T cells to bind and eliminate malignant B cells by releasing toxic proteins into the target B cells.

Cevostamab is a first-in-class FcRH5xCD3 T-cell engaging bispecific antibody., it can simultaneously bind to FcRH5 on myeloma cells and CD3 on the surface of T cells, bringing T cells close to tumor cells and eliminating them. FcRH5 is a unique differentiated target expressed on nearly 100% of myeloma cells. The structure of cevostamab is similar to natural human antibodies but contains two Fab regions, one targeting FcRH5 and the other targeting CD3. This dual-targeting action activates and redirects the patient’s existing endogenous T cells to bind with FcRH5-expressing myeloma cells, eliminating these malignant target cells by releasing cytotoxic proteins into them.TumorCells. Currently, cevostamab is being developed for the treatment of patients with relapsed or refractory multiple myeloma (R/R MM).

——Preliminary results from the Phase 1b CO41942 study indicate that the combination regimen of mosunetuzumab + lenalidomide shows encouraging preliminary efficacy and tolerable safety in patients with relapsed or refractory follicular lymphoma (R/R FL) who have received at least one prior treatment.

——Results from the Phase 1b/2 GO40516 study indicate that the combination regimen of mosunetuzumab + Polivy (polatuzumab vedotin-piiq) demonstrates favorable efficacy and safety in patients with aggressive, relapsed or refractory non-Hodgkin lymphoma (R/R NHL) who have previously received multiple treatment regimens:The objective response rate (ORR) reached 65.0%, and the complete response rate (CR) reached 48.3%.Cytokine release syndrome (CRS) occurred in 18% of patients, with all events occurring in Cycle 1 and being Grade 1-2.

——Phase 1/2b NP30179 Dose-Escalation Study evaluated the efficacy and safety of glofitamab as a monotherapy and glofitamab + Gazyva (obinutuzumab) combination therapy in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (R/R B-NHL). The results showed encouraging efficacy in R/R FL and R/R mantle cell lymphoma (MCL). Preliminary results in heavily pretreated R/R FL patients demonstrated high response rates across all treatment groups, including high-risk subgroups:The ORR of the glofitamab monotherapy group was 81.0%, and the ORR of the glofitamab + Gazyva combination therapy group was 100%.. For the previousR/R MCL patients treated with glofitamab after receiving Gazyva had an ORR of 81.0%.In the study, the most common adverse event was CRS, with most events being low-grade (grade 1-2).

——Results from the Phase 1b/2 NP39488 study showed that the combination regimen of glofitamab + Polivy demonstrated encouraging preliminary efficacy in difficult-to-treat R/R diffuse large B-cell lymphoma (DLBCL) patients, with a tolerable safety profile.Median follow-up was 3.2 months (95% CI: 1.4-3.5), ORR was 73.0%, CR was 51.5%, and duration of response was ≥6 months.No grade 3 or higher CRS events were observed, and the safety of the combination therapy was consistent with the safety of monotherapy.

——Data from the Phase 1 GO39775 dose-escalation and expansion study indicate that cevostamab, the first-in-class FcRH5xCD3 bispecific antibody, induced a clinically meaningful, target dose-dependent increase in ORR without increasing the CRS rate in heavily pretreated R/R multiple myeloma (MM) patients.The ORR of the 160 mg dose group was 54.5%.The results of the 2-step dose escalation showed that, compared with the single-step dose escalation, this method helps to alleviate CRS and may improve safety. (Bioon.com)

Source of the original text:Genentech Presents Pivotal Data at ASH 2021 for Novel Cancer Immunotherapy Mosunetuzumab