Regeneron's BCMAxCD3 Bispecific Antibody REGN5458 Demonstrates 75% Overall Response Rate in Heavily Pretreated Relapsed/Refractory Multiple Myeloma

News on January 21, 2022 /BioValleyBIOON/ -- Regeneron announced new results from the higher-dose cohorts of the bispecific antibody REGN5458 (BCMAxCD3) for the treatment of relapsed or refractory multiple myeloma (R/R MM). The results come from the Phase 1 portion of an open-label Phase 1/2 dose-escalation trial, with data showing:The overall response rate (ORR) across all dose groups was 51%, while the ORR increased to 75% in patients receiving higher doses (200-800mg) of REGN5458.

Bispecific antibodies are a new type ofTumorImmunotherapy treatments can simultaneously target two different antigens. One arm directly binds to a specific antigen on cancer cells, while the other activates the patient.AutoimmunityThe T cells in the system move closer to the cancer cells and kill them.

REGN5458 is a bispecific antibody designed to bind to B-cell maturation antigen (BCMA), which is highly expressed on the surface of multiple myeloma cells, and the CD3 receptor on the surface of cytotoxic T cells, bringing them together to activate T cells to kill cancer cells.Currently, REGN5458 is being evaluated in the potential registrational Phase 2 portion of the trial, with enrollment expected to be completed in 2022.

This open-label, Phase 1/2 dose-escalation trial is evaluating REGN5458 for the treatment of patients with relapsed/refractory multiple myeloma (R/R MM) who have received at least three prior lines of therapy or are double-refractory. All patients have been previously treated with a proteasome inhibitor, an immunomodulatory agent, and a CD38 antibody.Part 1 of the trial mainly evaluated the safety, tolerability, and dose-limiting toxicity of REGN5458, with efficacy as a secondary endpoint. Part 2 will further assess the efficacy of REGN5458.TumorActivity and safety.

As of the data cutoff, 73 patients had received REGN5458 treatment at doses ranging from 3 to 800 mg for up to 12 months. These patients had a median of 5 prior lines of therapy; 38% (n=28) were penta-refractory, and 90% (n=66) were refractory to their last line of therapy.

At higher dose levels (200-800 mg), the overall response rate (ORR) was 75% (n=18/24); among all enrolled patients, the ORR was 51% (n=37/73). Most responses occurred within the first month of treatment and deepened over time. Among responders across all dose groups: (1) 43% (n=16/37) achieved complete response (CR), and 40% of evaluable CR patients (n=4/10) were minimal residual disease (MRD) negative. (2) The probability of event-free survival at 8 months from the time of response was 90% (95% CI: 73%, 97%), defined as no disease progression or death; as of the data cutoff, the estimated median duration of response had not been reached. (3) Responses were rapid, typically occurring within the first month of treatment, and continued to deepen with prolonged treatment; the follow-up duration for the high-dose group is currently significantly shorter.

Safety was generally consistent across all dose levels. Cytokine release syndrome (CRS) was reported in 38% of patients (n=28), with the majority being Grade 1 (n=25) and no cases >Grade 3. The most common treatment-emergent adverse events (TEAEs) were fatigue (n=33), fever (n=26), nausea (n=24), andAnemia(n=23). The most common >3 grade TEAEs were anemia (n=17), neutropenia (n=16), lymphopenia (n=14), thrombocytopenia (n=10), and pneumonia (n=9). There were 5 deaths in the trial, all due to infections, and the researchers confirmed that all were unrelated to the study drug.

The investigator of this trial, Karmanos Cancer InstituteTumor"Patients with multiple myeloma often face a long and challenging journey, and over time, most patients become refractory to multiple treatment regimens. For patients with a high disease burden and highly refractory disease, the available treatment options are very limited. The data released today show that REGN5458 has a high response rate in these patients, especially at higher dose levels," said Dr. Jeffrey Zonder, Professor of Medicine.

L. Andres Sirulnik, M.D., Senior Vice President of Regeneron's Hematology Clinical Development, stated: "In multiple myeloma, multi-drug regimens typically show the highest response rates early in the course of the disease. It is highly encouraging that we observed a 75% response rate with higher-dose REGN5458 monotherapy in patients with more advanced disease. This adds to the growing body of promising data for our CD3 bispecific antibodies, supporting the continued development of this class across various blood cancers." (Bioon.com)

Source of Original Text:NEW REGN5458 (BCMAXCD3) PHASE 1 DATA SHOW 75% RESPONSE RATE AT HIGHEST DOSE LEVELS STUDIED IN PATIENTS WITH HEAVILY PRETREATED MULTIPLE MYELOMA