Isatuximab combination reduces mortality risk in Phase III trial

4th June 2019 (Last Updated June 4th, 2019 00:00)

Sanofi has reported positive outcomes from the Phase III ICARIA-MM clinical trial that assessed a combination of its isatuximab with pomalidomide and dexamethasone.

Isatuximab combination reduces mortality risk in Phase III trial
Myeloma cells produce monoclonal proteins of varying types, most commonly immunoglobulins (antibodies) and free light chains. Credit: Manu5.

Sanofi has reported positive outcomes from the Phase III ICARIA-MM clinical trial that assessed a combination of its isatuximab with pomalidomide and dexamethasone.

As part of the trial, the combination reduced the risk of disease progression or death by 40% in patients with relapsed/refractory multiple myeloma (RRMM).

The randomised, open-label, multi-centre trial compared the isatuximab combination to pomalidomide and dexamethasone (pom-dex) alone in a total of 307 participants across 24 countries.

Developed by Sanofi, isatuximab is an investigational monoclonal antibody (mAb) designed to target a specific epitope on the cluster of differentiation 38 (CD38) receptor.

It induces multiple mechanisms of action that are believed to be involved in the promotion of programmed tumour cell death and immunomodulatory activity.

During the ICARIA-MM trial, the isatuximab combination led to statistically significant improvement in progression-free survival (PFS), demonstrating a longer median PFS, compared to pom-dex alone.

The combination therapy also showed a significantly greater overall response rate, a higher very good partial response (VGPR) rate and a longer duration of response.

Patients treated with the isatuximab combination had longer time-to-next-treatment, compared to those in the pom-dex arm. Results also revealed a trend towards an overall survival benefit with the combination therapy.

In the Phase III trial, 86.8% of patients on the isatuximab combination therapy experienced adverse events (AE) of Grade ≥3, compared with 70.5% of subjects treated with pom-dex.

Furthermore, 7.2% of participants in the isatuximab regimen arm discontinued treatment due to AEs, compared with 12.8% in the pom-dex group. The figure was 7.9% versus 9.4% deaths due to AEs, respectively.

Sanofi is currently studying isatuximab in different Phase III trials in combination with existing therapies across the multiple myeloma treatment continuum.

The drug is being developed for the treatment of other hematologic malignancies and solid tumours.