Sanofi has presented results from the pivotal Phase 3 ICARIA-MM trial, demonstrating that isatuximab added to pomalidomide and dexamethasone showed statistically significant improvements in progression free survival and overall response rates compared to pomalidomide and dexamethasone alone in patients with relapsed/refractory multiple myeloma (RRMM). The ICARIA-MM trial studied a difficult-to-treat population of elderly patients who had been previously treated with multiple therapies.
These findings were presented at the 2019 American Society of Clinical Oncology (ASCO) vAnnual Meeting in Chicago. Isatuximab is an investigational monoclonal antibody that targets a specific epitope on the CD38 receptor of a malignant plasma cell.
“The ICARIA-MM trial demonstrated that isatuximab in combination with pomalidomide and dexamethasone, showed a significant improvement in progression free survival by five months, in comparison to pomalidomide and dexamethasone alone,” said Professor Gordon Cook, Professor of Haematology & Myeloma Studies, Clinical Director (Haematology), Clinical Trials Research Unit at St James’ University Hospital, Leeds. “The results presented today are significant given this trial was conducted with difficult-to-treat patient populations, where there remains an unmet need for patients living with relapsed/refractory multiple myeloma.”
Multiple myeloma is the second most common haematological cancer, with more than 5,500 people diagnosed each year in the UK. It is estimated that 17,500 people live with this disease at any one time. Multiple myeloma remains incurable, resulting in significant disease burden. Isatuximab combination therapy showed a statistically significant improvement in median progression free survival of greater than five months compared to pomalidomide and dexamethasone alone [n=307 (11.53 months vs. 6.47 months, p=0.001) HR 0.596 (95% CI 0.44-0.81)]. Compared to pomalidomide and dexamethasone alone, isatuximab combination therapy demonstrated a significantly greater overall response rate (60% vs. 35%, p<0.0001). In additional analyses, isatuximab combination therapy compared to pomalidomide and dexamethasone alone showed a consistent treatment benefit in the following subgroups: patients 75 years and older, patients with renal insufficiency, and patients who were refractory to lenalidomide. Results were confirmed by independent review committee.
In addition, the study also included the following results for the isatuximab combination therapy:
- Although not yet mature, data revealed a trend towards an overall survival benefit associated with isatuximab combination therapy compared to pomalidomide and dexamethasone alone.
- Isatuximab combination therapy demonstrated shorter median time to first response versus pomalidomide and dexamethasone alone (35 days vs. 60 days).
Dr Marc Moodley, Medical Director for Sanofi Genzyme said: “The ICARIA-MM data presented today at ASCO is the first Phase 3 study of an anti-CD38 monoclonal antibody in combination with pomalidomide and dexamethasone. The positive outcomes from this study take us a step towards bringing this investigational compound forward as a potential new therapeutic option for patients.”
Adverse events (AEs) of Grade ≥3 were observed in 86.8% of isatuximab combination therapy patients vs. 70.5% of pomalidomide and dexamethasone patients, however few patients discontinued therapy due to AEs (7.2% vs 12.8% respectively).1 7.9% vs. 9.4% of patients died due to AEs, respectively; infections of Grade ≥3 were seen in 42.8% vs. 30.2% of patients, respectively; and Grade ≥3 neutropenia was seen in 84.9% (febrile 11.8%) vs. 70.1% (febrile 2.0%) of patients, respectively. Infusion reactions were reported in 38.2% (2.6% grade 3-4) of isatuximab combination therapy patients.