Roche's First-in-Class FcRH5xCD3 Bispecific Antibody Cevostamab Achieves 53% Overall Response Rate in Heavily Pretreated Relapsed/Refractory Multiple Myeloma

December 11, 2020 /BioValleyBIOON/ -- Roche recently announced for the first time the clinical safety and efficacy data of cevostamab (BFCR4350A), the third bispecific antibody in its hematologic malignancies pipeline. The results showed that cevostamab demonstrated significant efficacy and a manageable safety profile in patients with relapsed or refractory multiple myeloma (R/R MM) who had previously received multiple therapies.

Cevostamab is a first-in-class FcRH5xCD3 T-cell-engaging bispecific antibody that functions by simultaneously targeting FcRH5 on myeloma cells and CD3 on the surface of T cells. FcRH5 is a unique, differentiated target expressed on nearly 100% of myeloma cells.

The structure of cevostamab resembles that of natural human antibodies but contains two Fab regions, one targeting FcRH5 and the other targeting CD3. This dual-targeting mechanism activates and redirects the patient’s existing endogenous T cells to bind with myeloma cells expressing FcRH5, thereby eliminating these malignant target cells by releasing cytotoxic proteins into them.TumorCell.

FcRH5xCD3 (Image source: PMID 32659909)

Currently, Roche is conducting the dose-escalation and expansion Phase I GO39775 study (NCT03275103) to evaluate cevostamab as monotherapy in adult patients with relapsed/refractory multiple myeloma (R/R MM) who are heavily pre-treated (i.e., have received multiple prior treatment regimens).

Patients in this study had received a median of 6 prior regimens. The study allowed enrollment of patients with relapsed/refractory multiple myeloma (R/R MM) who had previously received treatments including CAR-T cell therapy, T-cell-engaging bispecific antibodies, bispecific T-cell engagers (BiTEs), and antibody-drug conjugates (ADCs, including BCMA-targeted therapies). This patient population has an urgent unmet need for new treatment options, as there are currently no effective, appropriate, or tolerable therapies available.

The clinical safety and efficacy data disclosed for the first time indicate that, at effective doses,The overall response rate (ORR) for cevostamab treatment was 53% (n=18/34).Notably, treatment responses were observed in high-risk patients, including those with disease refractory to five different classes of medications.(five-times refractory) patients (ORR=41%, n=7/17)and thosePatients who had previously received anti-BCMA therapy (ORR=63%, n=5/8).

In this study, the safety profile of cevostamab was manageable, with cytokine release syndrome (CRS) being the most common treatment-related adverse event (76%). The majority of CRS events were Grade 1–2 (Grade 1: 34%; Grade 2: 40%) and occurred during Cycle 1. One patient experienced Grade 3 CRS (2%); no Grade 4 or 5 CRS events were observed. (Bioon.com)

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