Isatuximab + VRd for Multiple Myeloma

(IMROZ Trial)

Recruiting at 312 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Sanofi

Must be taking: Bortezomib, Lenalidomide, Dexamethasone

Disqualifiers: Age < 18, Prior treatment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

475 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called isatuximab added to a standard treatment mix. It targets patients with newly diagnosed multiple myeloma who can't have a transplant. Isatuximab helps the immune system destroy cancer cells, while the other drugs kill cancer cells and reduce inflammation.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug combination Isatuximab + VRd for treating multiple myeloma?

Research shows that Isatuximab, when combined with other drugs like pomalidomide and dexamethasone, significantly improves progression-free survival (the time during which the disease does not get worse) and tumor response in patients with relapsed or refractory multiple myeloma. Additionally, a study on newly diagnosed patients using Isatuximab with bortezomib, lenalidomide, and dexamethasone (VRd) showed a high overall response rate, with many patients achieving complete response or better. ^{1 2 3 4 5}

What makes the drug Isatuximab + VRd unique for treating multiple myeloma?

The Isatuximab + VRd treatment is unique because it combines isatuximab, an anti-CD38 monoclonal antibody, with a regimen of bortezomib, lenalidomide, and dexamethasone, which has shown high response rates in newly diagnosed multiple myeloma patients who are not eligible for stem cell transplantation. This combination aims to improve outcomes by targeting multiple pathways involved in the disease. ^{1 2 3 5 6}

Research Team

Clinical Sciences & Operations

Principal Investigator

Sanofi

Eligibility Criteria

This trial is for adults with newly diagnosed multiple myeloma who can't have a transplant because they're over 65 or under 65 with other health issues. They must have measurable disease signs and agree to use contraception if necessary. It's not for those under 18, previously treated for myeloma, or with certain health conditions that could interfere.

Inclusion Criteria

I have been diagnosed with multiple myeloma.

I am over 65 or have health issues that prevent a bone marrow transplant for my newly diagnosed multiple myeloma.

I have been diagnosed with multiple myeloma.

Exclusion Criteria

My organ functions are not within the required range.

I am a male and agree to follow contraceptive advice during the study.

I am under 18 years old.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Up to 4 weeks

Induction Treatment

Participants receive induction treatment with 4 cycles of 6-week duration each, involving bortezomib, lenalidomide, and dexamethasone, with or without isatuximab

24 weeks

Continuous Treatment

Participants continue treatment with 4-week cycles involving lenalidomide and dexamethasone, with or without isatuximab

Variable, based on individual response

Crossover Period

Participants may crossover to receive isatuximab, lenalidomide, and dexamethasone in 4-week cycles

Variable, based on individual response

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 100 months after the first participant in

Treatment Details

Interventions

• Bortezomib
• Dexamethasone
• Isatuximab SAR650984
• Lenalidomide

Trial Overview The study tests whether adding Isatuximab (SAR650984) to the combo of Bortezomib, Lenalidomide, and Dexamethasone improves survival without cancer progression in new multiple myeloma patients ineligible for transplant compared to just the three-drug combo.

Participant Groups

Group I: Isatuximab/Lenalidomide/Dexamethasone = IRd crossover arm Experimental Treatment 3 Interventions

4-weeks cycles with IV isatuximab + oral lenalidomide + IV or oral dexamethasone

Group II: Isatuximab/Bortezomib/Lenalidomide/Dexamethasone = IVRd arm Experimental Treatment 4 Interventions

1. Induction treatment with 4x6-week cycles with intravenous (IV) isatuximab + subcutaneous (SC) bortezomib + oral lenalidomide + IV or oral dexamethasone 2. Continuous treatment with 4-week cycles with IV isatuximab + oral lenalidomide + IV or oral dexamethasone

Group III: Bortezomib/Lenalidomide/Dexamethasone = VRd arm Active Control 3 Interventions

1. Induction treatment with 4x6-week cycles with SC bortezomib + oral lenalidomide + IV or oral dexamethasone 2. Continuous treatment with 4-week cycles with oral lenalidomide + IV or oral dexamethasone

Bortezomib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in United States as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Canada as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Japan as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Who Is Running the Clinical Trial?

Sanofi

Lead Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Findings from Research

Isatuximab, an anti-CD38 monoclonal antibody, significantly improves progression-free survival and tumor response when combined with pomalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma, based on phase III studies.

The combination therapies involving isatuximab were generally well tolerated, maintaining health-related quality of life and showing a manageable safety profile without new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab: A Review of Its Use in Multiple Myeloma. Frampton, JE.[2022]

In a study of 24 patients with relapsed/refractory multiple myeloma (RRMM) showing only biochemical progression, the combination of isatuximab and dexamethasone with methylprednisolone resulted in a 63% overall response rate and a 79% clinical benefit rate, indicating its efficacy.

The treatment was well tolerated, with only 5 instances of Grade ≥3 adverse events, primarily lymphocytopenia, and no severe complications related to respiratory infections, anemia, or thrombocytopenia, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of isatuximab in combination with steroids for the treatment of relapsed/refractory multiple myeloma patients exhibiting only biochemical progression-A single center retrospective study. Regidor, BS., Jew, S., Goldwater, MS., et al.[2023]

In a phase 2 study involving 164 patients with relapsed/refractory multiple myeloma, the combination of isatuximab and dexamethasone showed a significantly higher overall response rate (43.6%) compared to isatuximab alone (23.9%).

The addition of dexamethasone did not increase safety concerns, as the incidence of serious adverse events, including infections, was similar between the two treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab as monotherapy and combined with dexamethasone in patients with relapsed/refractory multiple myeloma. Dimopoulos, M., Bringhen, S., Anttila, P., et al.[2023]

In the phase 3 ICARIA-MM trial, isatuximab combined with pomalidomide-dexamethasone significantly improved median progression-free survival (mPFS) in high-risk multiple myeloma patients, showing 7.5 months compared to 3.7 months with standard treatment.

Despite a higher incidence of grade ≥3 adverse events in high-risk patients receiving isatuximab (95.7% vs. 67.6% in the control group), the treatment did not lead to increased discontinuation or treatment-related mortality, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subgroup analysis of ICARIA-MM study in relapsed/refractory multiple myeloma patients with high-risk cytogenetics. Harrison, SJ., Perrot, A., Alegre, A., et al.[2021]

In a Phase 1b study involving 73 patients with newly diagnosed multiple myeloma who were ineligible for autologous stem cell transplantation, the combination of isatuximab with bortezomib-lenalidomide-dexamethasone (Isa-VRd) showed a remarkable overall response rate of 98.6%, with over half of the patients achieving a complete response.

While 79.5% of patients experienced grade ≥3 treatment-emergent adverse events, the pharmacokinetics of isatuximab remained consistent, indicating that the combination treatment does not affect its metabolism, supporting further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of isatuximab plus bortezomib, lenalidomide, and dexamethasone in patients with newly diagnosed multiple myeloma ineligible/with no immediate intent for autologous stem cell transplantation. Ocio, EM., Perrot, A., Bories, P., et al.[2023]

Isatuximab, a CD38 monoclonal antibody, is effective for treating adults with relapsed/refractory multiple myeloma, particularly in combination with pomalidomide and dexamethasone after at least two prior therapies.

Nursing care for patients receiving isatuximab involves careful monitoring for adverse events like infusion reactions and neutropenia, which is crucial for providing effective patient education and management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab: Nursing Considerations for Use in the Treatment of Multiple Myeloma. Wilmoth, J., Colson, K., Dubin, F., et al.[2022]

References

1. France pubmed.ncbi.nlm.nih.gov

Isatuximab: A Review of Its Use in Multiple Myeloma. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Efficacy of isatuximab in combination with steroids for the treatment of relapsed/refractory multiple myeloma patients exhibiting only biochemical progression-A single center retrospective study. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Isatuximab as monotherapy and combined with dexamethasone in patients with relapsed/refractory multiple myeloma. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Subgroup analysis of ICARIA-MM study in relapsed/refractory multiple myeloma patients with high-risk cytogenetics. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of isatuximab plus bortezomib, lenalidomide, and dexamethasone in patients with newly diagnosed multiple myeloma ineligible/with no immediate intent for autologous stem cell transplantation. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Isatuximab: Nursing Considerations for Use in the Treatment of Multiple Myeloma. [2022]