Isatuximab + Carfilzomib + Dexamethasone for Multiple Myeloma

(SubQSA Trial)

Recruiting at 8 trial locations

Overseen By Trial Transparency email recommended (Toll free for US & Canada)

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sanofi

Must not be taking: Anti-CD38, Carfilzomib, Dexamethasone

Disqualifiers: Primary refractory MM, Allergy, others

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

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

Compensation: Varies

Number of Visits: 29

Duration: Up to 32 months

64 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary purpose of this study is to assess the efficacy (overall response rate) of subcutaneous (SC) via on body delivery system (SC-OBDS) isatuximab in combination with weekly carfilzomib and dexamethasone (Kd) in adult participants with RRMM having received 1 to 3 prior lines of therapy.

Will I have to stop taking my current medications?

The trial requires that you stop any anti-myeloma drug treatment, including dexamethasone, at least 14 days before starting the study medication. If you're on such medications, you'll need to pause them before participating.

What data supports the effectiveness of the drug combination Isatuximab, Carfilzomib, and Dexamethasone for treating multiple myeloma?

Research shows that the combination of Isatuximab, Carfilzomib, and Dexamethasone significantly improved progression-free survival (the time during and after treatment that a patient lives with the disease without it getting worse) in patients with relapsed multiple myeloma compared to Carfilzomib and Dexamethasone alone. ^{1 2 3 4 5}

What makes the drug combination of Isatuximab, Carfilzomib, and Dexamethasone unique for treating multiple myeloma?

This drug combination is unique because Isatuximab, an anti-CD38 monoclonal antibody, is added to Carfilzomib and Dexamethasone, significantly improving progression-free survival in patients with relapsed multiple myeloma compared to Carfilzomib and Dexamethasone alone. ^{1 2 3 5 6}

Eligibility Criteria

This trial is for adults with Multiple Myeloma who've had 1-3 prior treatments. They must have measurable levels of myeloma proteins in their blood or urine and agree to use contraception. It's not open to pregnant or breastfeeding women, those planning pregnancy, or anyone ineligible due to other medical conditions.

Inclusion Criteria

I have been diagnosed with multiple myeloma.

My tests show high levels of certain proteins indicating my condition.

I have had 1 to 3 treatments for my multiple myeloma.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive isatuximab via SC-OBDS in combination with weekly carfilzomib and dexamethasone. Treatment cycles are 28 days each.

Up to 32 months

Weekly visits during each 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment discontinuation

3 months

1 visit 30 days after last dose, then follow-up for 90 days

Treatment Details

Interventions

• Carfilzomib
• Isatuximab

Trial Overview The study tests a new way to give Isatuximab (via SC-OBDS) combined with Carfilzomib and Dexamethasone in patients whose Multiple Myeloma has returned after treatment. The goal is to see how well this combination works when given weekly.

Participant Groups

Group I: Isatuximab in combination with weekly carfilzomib and dexamethasone Experimental Treatment 7 Interventions

Participants will receive isatuximab via SC-OBDS administration in combination with weekly carfilzomib and dexamethasone. Isatuximab will be administered on days 1, 8, 15 and 22 for Cycle 1 and then on days 1, 15 for subsequent cycles. Carfilzomib will be administered intravenously (IV) at a starting dose on Day 1 of Cycle 1 and then escalated dose on Days 8 and 15 of Cycle 1, followed by Days 1, 8 and 15 of subsequent cycles. Dexamethasone will be given on Days 1, 8, 15, and 22 of Cycle 1 and then on Days 1, 8 and 15 of subsequent cycles. Dexamethasone will be administered IV on Cycle 1 Day 1, and IV or PO in the subsequent administrations. 1 cycle = 28 days.

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

In a phase 3 study involving 302 patients with relapsed multiple myeloma, the addition of isatuximab to carfilzomib-dexamethasone significantly improved progression-free survival compared to carfilzomib-dexamethasone alone, with a hazard ratio of 0.53, indicating a 47% reduction in the risk of disease progression.

While the isatuximab group experienced a higher rate of treatment-emergent adverse events (77% vs. 67%), the overall safety profile was similar, with no significant difference in fatal adverse events, suggesting that isatuximab can be safely integrated into treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial. Moreau, P., Dimopoulos, MA., Mikhael, J., et al.[2022]

In the Phase 3 IKEMA study, the combination of isatuximab (Isa) with carfilzomib (K) and dexamethasone (d) significantly improved progression-free survival (PFS) in East Asian patients with relapsed multiple myeloma compared to the carfilzomib and dexamethasone (Kd) regimen.

The Isa-Kd combination also showed higher rates of very good partial response (≥VGPR), complete response (CR), and minimal residual disease (MRD) negativity, while maintaining a safety profile consistent with the overall IKEMA population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab Plus Carfilzomib and Dexamethasone in East Asian Patients With Relapsed Multiple Myeloma: Updated IKEMA Subgroup Analysis. Kawano, Y., Kim, K., Min, CK., et al.[2023]

Carfilzomib, when used in combination with lenalidomide and dexamethasone, significantly prolongs progression-free survival (PFS) by 8.7 months in patients with relapsed multiple myeloma, based on results from the phase III ASPIRE study involving a multinational patient population.

The combination therapy has a manageable safety profile, with low incidences of severe adverse events, suggesting it is a viable treatment option for patients who have received prior therapies, although overall survival data is still pending.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib Triple Combination Therapy: A Review in Relapsed Multiple Myeloma. Hoy, SM.[2018]

Carfilzomib is a selective and irreversible proteasome inhibitor that leads to tumor cell growth arrest and apoptosis, making it an effective treatment for multiple myeloma.

Initially approved for advanced cases, carfilzomib is now also used in earlier relapse settings, often in combination with lenalidomide and dexamethasone, showing improved clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib boosted combination therapy for relapsed multiple myeloma. Steiner, RE., Manasanch, EE.[2020]

The combination of daratumumab, carfilzomib, and dexamethasone has shown strong clinical efficacy in treating relapsed multiple myeloma, particularly in patients whose disease is refractory to lenalidomide.

This triplet therapy has been approved by the US FDA for use in relapsed multiple myeloma, highlighting its significance as a treatment option in a setting with limited effective alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib in combination with daratumumab in the management of relapsed multiple myeloma. Touzeau, C., Antier, C., Moreau, P.[2021]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial. [2022]

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

Isatuximab Plus Carfilzomib and Dexamethasone in East Asian Patients With Relapsed Multiple Myeloma: Updated IKEMA Subgroup Analysis. [2023]

3. France pubmed.ncbi.nlm.nih.gov

Carfilzomib Triple Combination Therapy: A Review in Relapsed Multiple Myeloma. [2018]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Carfilzomib boosted combination therapy for relapsed multiple myeloma. [2020]

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

Carfilzomib in combination with daratumumab in the management of relapsed multiple myeloma. [2021]

6. France pubmed.ncbi.nlm.nih.gov

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