Isatuximab + Carfilzomib for Multiple Myeloma

Recruiting at 5 trial locations

Overseen By Phu Lam

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Thomas Martin, MD

Must not be taking: Corticosteroids, Anti-infectives

Disqualifiers: Other malignancy, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: 30

Duration: 28 days per cycle, up to 8 cycles

83 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase Ib trial studies the side effects and best dose of isatuximab when given together with carfilzomib with or without dexamethasone and lenalidomide in treating patients with multiple myeloma that has returned after a period of improvement (relapsed) or has not respond to previous treatment (refractory). Immunotherapy with monoclonal antibodies, such as isatuximab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as dexamethasone and lenalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving isatuximab and carfilzomib with or without dexamethasone and lenalidomide may be a better treatment for patients with multiple myeloma.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had prior SAR650984 anti-CD38 antibody therapy, and you must be more than 4 weeks from your last dose of carfilzomib if you have taken it before. It's best to discuss your current medications with the study doctor.

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 improves 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 using Carfilzomib and Dexamethasone alone. This combination is generally well tolerated and maintains the quality of life for patients. ^{1 2 3 4 5}

Is the combination of Isatuximab and Carfilzomib safe for humans?

The combination of Isatuximab and Carfilzomib has been generally well tolerated in clinical trials for multiple myeloma, with a manageable safety profile and no new safety concerns reported. ^{1 2 3 6 7}

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

The combination of Isatuximab, an anti-CD38 monoclonal antibody, with Carfilzomib, a proteasome inhibitor, significantly improves progression-free survival in patients with relapsed multiple myeloma compared to Carfilzomib alone, offering a novel approach by targeting different mechanisms in the cancer cells. ^{1 2 3 4 6}

Research Team

Thomas Martin, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for adults with multiple myeloma that has come back or hasn't responded to treatment. They should have had at least one but no more than three prior treatments and can't be very sick (ECOG <=2). People who've had certain other cancers, serious heart issues, or major procedures recently can't join. Participants need to understand the study and agree to use birth control if needed.

Inclusion Criteria

You need to have specific test results from a clinical laboratory.

You have a medical condition that can be measured using specific guidelines.

I am following the required pregnancy prevention measures.

Exclusion Criteria

I have had serious heart issues or a heart attack in the last 6 months, or my high blood pressure is not well controlled.

I do not have severe or painful nerve damage.

I had a stem cell transplant less than 12 weeks ago.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive isatuximab, carfilzomib, and dexamethasone in cycles of 28 days for up to 8 cycles, with potential continuation if clinical benefit is observed

28 days per cycle, up to 8 cycles

Multiple visits per cycle for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Up to 3 years

Follow-up at 30 and 60 days, then every 3 months

Treatment Details

Interventions

• Carfilzomib
• Dexamethasone
• Isatuximab

Trial Overview The trial tests a combination of drugs: Isatuximab (a monoclonal antibody), Carfilzomib (blocks cancer cell growth), Dexamethasone, and Lenalidomide (chemotherapy drugs). It aims to find the best dose of Isatuximab with these drugs in patients whose multiple myeloma has returned or is resistant.

Participant Groups

Group I: Arm II (40 mg dexamethasone, isatuximab, carfilzomib) Experimental Treatment 3 Interventions

40 mg dexamethasone IV given on Days 1, 8, 15 and 22 (use as premed to isatuximab). All patients will receive a fixed dose of Isatuximab (SAR650984) according to the assigned dose. Patients receive isatuximab IV over 4-6 hours on day 1, 3-4 hours on Day 8, 15, and 22 of cycle 1 and then on days 1 and 15 of subsequent cycle (patients may be eligible for rapid siatuximab given over 75 minutes), and carfilzomib IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm I (20 mg dexamethasone, isatuximab, carfilzomib) Experimental Treatment 3 Interventions

20 mg dexamethasone IV given on days 1, 8, 15, 22 (pre- SAR650984 and carfilzomib), then dexamethasone 4 IV or PO mg Day 2, 9, 16. All patients will receive a fixed dose of Isatuximab (SAR650984) according to their assigned dose cohort. Patients receive isatuximab IV over 4-6 hours on days 1 and 15 of every cycle for the starting cohort, and days 1, 8, 15, and 22 of cycle 1 and days 1 and 15 of subsequent cycles. Carfilzomib IV will be administered over 10 minutes on days 1, 2, 8, 9, 15, and 16 . Treatment repeats every 28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients may continue treatment after 8 courses if clinical benefit is present at the investigator's discretion (carfilzomib may be switched to days 1, 2, 15, and 16 after 8 cycles per investigator discretion).

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

Approved in United States as Kyprolis for:

• Multiple myeloma

Approved in European Union as Kyprolis for:

• Multiple myeloma

Approved in Canada as Kyprolis for:

• Multiple myeloma

Approved in Japan as Kyprolis for:

• Multiple myeloma

Who Is Running the Clinical Trial?

Thomas Martin, MD

Lead Sponsor

Trials

4

Recruited

130+

Amgen

Industry Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Sanofi

Industry 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

The combination of isatuximab and carfilzomib was well tolerated in 33 patients with relapsed and refractory multiple myeloma, showing no unexpected toxicity and an overall response rate of 70%.

With a median follow-up of 26.7 months, the treatment resulted in a median progression-free survival of 10.1 months, indicating its effectiveness even in heavily pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1b trial of isatuximab, an anti-CD38 monoclonal antibody, in combination with carfilzomib as treatment of relapsed/refractory multiple myeloma. Martin, TG., Shah, N., Richter, J., et al.[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]

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-containing combinations as frontline therapy for multiple myeloma showed a high overall response rate of 94% and a complete response rate of 21% across 13 trials involving 704 subjects.

The combination of carfilzomib with lenalidomide and dexamethasone (CFZ-LEN-DEX) resulted in a significantly higher complete response rate of 49% compared to other combinations, indicating it may be the most effective regimen for newly diagnosed patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib-containing combinations as frontline therapy for multiple myeloma: A meta-analysis of 13 trials. Sheng, Z., Li, G., Li, B., et al.[2018]

In a Phase 3 trial with 302 patients suffering from relapsed/refractory multiple myeloma, the combination of isatuximab with carfilzomib-dexamethasone significantly prolonged progression-free survival (PFS) to a median of 35.7 months compared to 19.2 months for carfilzomib-dexamethasone alone.

The addition of isatuximab also resulted in higher rates of complete response (44.1% vs 28.5%) and minimal residual disease negativity (33.5% vs 15.4%), indicating improved efficacy without compromising safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab, carfilzomib, and dexamethasone in patients with relapsed multiple myeloma: updated results from IKEMA, a randomized Phase 3 study. Martin, T., Dimopoulos, MA., Mikhael, J., et al.[2023]

References

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

Phase 1b trial of isatuximab, an anti-CD38 monoclonal antibody, in combination with carfilzomib as treatment of relapsed/refractory multiple myeloma. [2021]

2. France pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

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

4. 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]

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

Carfilzomib-containing combinations as frontline therapy for multiple myeloma: A meta-analysis of 13 trials. [2018]

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

Isatuximab, carfilzomib, and dexamethasone in patients with relapsed multiple myeloma: updated results from IKEMA, a randomized Phase 3 study. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Isatuximab plus carfilzomib and dexamethasone in relapsed multiple myeloma patients with high-risk cytogenetics: IKEMA subgroup analysis. [2023]