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03-Jun-2019

Phase 3 trial of isatuximab in combination with pomalidomide and dexamethasone, prolonged progression free survival in relapsed/refractory multiple myeloma compared to pomalidomide and dexamethasone alone1

*         Isatuximab, an investigational anti-CD38 monoclonal antibody, in combination with pomalidomide and dexamethasone prolonged progression free survival by five months compared to pomalidomide and dexamethasone alone1

*         Overall response rate was significantly greater with isatuximab combination therapy (60%) compared to pomalidomide and dexamethasone alone (35%)1

*         The first randomised Phase 3 trial to evaluate an antibody in combination with pomalidomide and dexamethasone was presented today at ASCO

GUILDFORD, UK – 2 June, 2019 – Today, results from the pivotal Phase 3 ICARIA-MM trial were presented, 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).1 The ICARIA-MM trial studied a difficult-to-treat population of elderly patients who had been previously treated with multiple therapies.1

These findings were presented at the 2019 American Society of Clinical Oncology (ASCO) Annual 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,[i] with more than 5,500 people diagnosed each year in the UK.[ii] It is estimated that 17,500 people live with this disease at any one time.3 Multiple myeloma remains incurable, resulting in significant disease burden.[iii]

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)].1 Compared to pomalidomide and dexamethasone alone, isatuximab combination therapy demonstrated a significantly greater overall response rate (60% vs. 35%, p<0.0001).1 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.1 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.1

·         Isatuximab combination therapy demonstrated shorter median time to first response versus pomalidomide and dexamethasone alone (35 days vs. 60 days).1

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.1 Infusion reactions were reported in 38.2% (2.6% grade 3-4) of isatuximab combination therapy patients.1

About ICARIA-MM

ICARIA-MM is a pivotal Phase 3 randomised, open-label, multi-centre trial evaluating isatuximab in combination with pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in patients with RRMM.1 The study enrolled 307 patients with RRMM across 96 centres spanning 24 countries, including sites in the UK.1 All patients had received a median three prior lines of anti-myeloma therapies, including at least two consecutive cycles of lenalidomide and a proteasome inhibitor given alone or in combination.1

During the trial, isatuximab was administered through an intravenous infusion at a dose of 10mg/kg once weekly for four weeks, then every other week for 28-day cycles in combination with standard doses of pomalidomide and dexamethasone for the duration of treatment.1

Topline results from ICARIA-MM were previously announced in February 2019.

About Isatuximab, a Monoclonal Antibody

Isatuximab is an investigational monoclonal antibody (mAb) targeting a specific epitope on the CD38 receptor. It is designed to trigger multiple, distinct mechanisms of action that are believed to directly promote programmed tumour cell death (apoptosis) and immunomodulatory activity. CD38 is highly and uniformly expressed on multiple myeloma cells and is a cell surface receptor target for antibody-based therapeutics in multiple myeloma and other malignancies. The clinical significance of these findings is under investigation.

Isatuximab is being developed by Sanofi, and is currently being evaluated in multiple ongoing Phase 3 clinical trials in combination with currently available treatments across the multiple myeloma treatment pathway. Isatuximab is an investigational agent and its safety and efficacy have not been evaluated by the European Medicines Agency, or any other regulatory authority.


[i] Kazandjian D. Multiple myeloma epidemiology and survival: A unique malignancy. Semin Oncol. 2016; 43 (6):676-681. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28061985.(Accessed May 2019).

[ii] About Myeloma booklet, Myeloma UK. Available at:

https://www.myeloma.org.uk/wp-content/uploads/2018/03/Myeloma-UK-Myeloma-An-Introduction.pdf. (Accessed May  2019).

[iii] Smith, D. and Yong, K. (2013). Multiple Myeloma. BMJ. 2013 Jun 26; 346:f3863. doi: 10.1136/bmj.f3863. (Accessed May 2019).

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Last Updated: 03-Jun-2019