Isatuximab + Carfilzomib + Dexamethasone for Multiple Myeloma

(SubQSA Trial)

Recruiting at 31 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of medications to evaluate their effectiveness in treating multiple myeloma, a type of blood cancer. The trial combines isatuximab (administered under the skin), carfilzomib (administered through a vein), and dexamethasone (a steroid) to determine if they can improve the overall response rate, which measures how well the cancer responds to treatment. Individuals who have previously undergone 1 to 3 treatments for multiple myeloma but still exhibit measurable signs of the disease may be suitable candidates for this study. Participants should not have received certain treatments too recently or have specific allergies to qualify. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of isatuximab, carfilzomib, and dexamethasone is safe for patients with multiple myeloma. Studies suggest that this combination, whether administered by manual injection or a wearable device, is generally well-tolerated.

However, some side effects require attention. The most common serious side effect is a drop in white blood cells, known as neutropenia, which occurred in about 25% of patients and can increase the risk of infections. Other side effects include a low platelet count, called thrombocytopenia, in 5% of patients, and infections in 7%.

These results indicate that while side effects can occur, they are manageable. This information provides a clearer understanding of what to expect regarding the treatment's safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Isatuximab, Carfilzomib, and Dexamethasone for treating multiple myeloma because it introduces a novel approach to managing the condition. Isatuximab is an antibody that targets CD38, a protein found on the surface of multiple myeloma cells, which helps the immune system attack and destroy cancer cells. This combination therapy is unique because it pairs the targeted action of Isatuximab with Carfilzomib, a proteasome inhibitor that disrupts the protein recycling process within cancer cells, leading to their death. Additionally, the delivery method for Isatuximab through subcutaneous administration could potentially improve patient convenience and comfort compared to the intravenous options typically used.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

Participants in this trial will receive a combination of isatuximab, carfilzomib, and dexamethasone. Studies have shown this combination to be effective for treating multiple myeloma, a type of blood cancer. In one study, 85% of patients experienced a positive response, with their cancer shrinking or stopping growth. Specifically, 18% of these patients had a complete response, with no cancer detected. Another study found that 85.1% of patients were still alive one year after starting this treatment. This evidence suggests that this combination can offer significant benefits for people with multiple myeloma. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12030129/

Efficacy and Safety of Isatuximab, Carfilzomib, ... The median overall survival was not reached, as in the pivotal trial, while the 1-year survival probability was 85.1%. Regarding the safety ...

2. nature.com nature.com/articles/s41408-023-00797-8

Isatuximab, carfilzomib, and dexamethasone in patients ... Longer-term outcomes with the anti-CD38 antibody isatuximab in combination with carfilzomib-dexamethasone (Isa-Kd) were evaluated in the randomized Phase 3 ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S235230262400070X

Isatuximab, carfilzomib, lenalidomide, and dexamethasone ... Our results confirm that the four-drug combination of isatuximab, carfilzomib, lenalidomide, and dexamethasone leads to deep and durable responses with a ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.7526

Efficacy and safety of isatuximab subcutaneous (SC) plus ... The study met its primary endpoint, demonstrating efficacy and safety of Isa SC administration in combination with Kd, either by manual injection or OBDS.

5. haematologica.org haematologica.org/article/view/12370

P173 | CLINICAL EFFICACY OF ISATUXIMAB PLUS ... The overall response rate was 85%, including 18% of patients achieving stringent complete response (sCR) or complete response (CR), and 39% very ...

6. ashpublications.org ashpublications.org/blood/article/146/1/52/535235/Isatuximab-carfilzomib-lenalidomide-and

Isatuximab, carfilzomib, lenalidomide, and dexamethasone ... The most common grade 3/4 adverse events were neutropenia (25%), thrombocytopenia (5%), and infections (7%); only 13% of patients reported any grade peripheral ...

7. asco.org asco.org/abstracts-presentations/ABSTRACT488358

Results of the phase 2 study IZALCO. The study met its primary endpoint, demonstrating efficacy and safety of Isa SC administration in combination with Kd, either by manual injection or OBDS.

8. mdpi.com mdpi.com/2072-6694/17/21/3494

Efficacy and Safety of Isatuximab Combination Therapy in ... Isatuximab treatment was associated with a substantially increased risk of grade 3 or 4 neutropenia in both NDMM (RR = 1.96, 95% CI: 1.26–3.07, p = 0.003) and ...