Isatuximab + Carfilzomib for Multiple Myeloma

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and assess the side effects of combining isatuximab (a monoclonal antibody) and carfilzomib (a proteasome inhibitor), with or without additional drugs like dexamethasone and lenalidomide. Researchers will test this combination on patients with multiple myeloma, a type of blood cancer that has returned or not responded to previous treatments. The trial will investigate whether this combination more effectively stops cancer growth. Individuals whose multiple myeloma has recurred after treatment or did not respond to past treatments might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this potentially groundbreaking therapy.

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.

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

Research has shown that the combination of isatuximab and carfilzomib, particularly with dexamethasone, is generally well-tolerated by patients with multiple myeloma. In earlier studies, serious side effects such as pneumonia occurred in about 25% of patients, while approximately 9% experienced upper respiratory infections. Most patients did not encounter these severe reactions.

Patients on this treatment lived without disease progression for an average of 41.7 months. Although some risks exist, many patients tolerate the treatment well enough to benefit from it. Discussing any concerns with a healthcare provider is crucial to understanding the full picture and determining if this trial is a suitable option. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Isatuximab and Carfilzomib for treating multiple myeloma because it offers a novel approach compared to existing therapies. Unlike traditional treatments, which often rely on drugs that target the cancer cell's DNA, Isatuximab is an antibody that specifically targets a protein on the surface of myeloma cells, potentially leading to more precise treatment. Carfilzomib, a proteasome inhibitor, works by blocking the cancer cells' ability to break down proteins, which leads to cell death. This combination aims to enhance the effectiveness of myeloma treatment by using these complementary mechanisms. Additionally, the regimen provides flexibility in dosing schedules, which may improve patient tolerance and outcomes.

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

This trial will evaluate the combination of isatuximab and carfilzomib, with varying doses of dexamethasone, for treating relapsed or hard-to-treat multiple myeloma. Studies have shown that this combination is effective, with patients living for a median of 41.7 months without disease progression, compared to 20.8 months with only carfilzomib and dexamethasone. This indicates that adding isatuximab significantly extends the time before cancer progresses. Additionally, some studies noted an 85.1% survival rate after one year, although the average overall survival time wasn't reached, indicating strong potential for long-term benefits. These findings suggest that isatuximab combined with carfilzomib could be a promising option for those with difficult-to-treat multiple myeloma. ^{1 3 4 5 6}

Who Is on the Research Team?

Thomas Martin, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

Citations

1. sarclisa.com sarclisa.com/previously-treated-trial-results

for adults with previously treated multiple myeloma Patients lived progression free for a median of 41.7 months with SARCLISA + Kyprolis (carfilzomib) and dexamethasone (Kd) vs 20.8 months with Kd alone.

2. kyprolis-hcp.com kyprolis-hcp.com/combinations/isa-kd-efficacy

Isa-Kd Efficacy | KYPROLIS® (carfilzomib) Isatuximab, carfilzomib, and dexamethasone in patients with relapsed multiple myeloma: updated results from IKEMA, a randomized Phase 3 study. Blood Cancer J.

3. 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 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03275285

Study Details | NCT03275285 | Multinational ... The purpose of this study it to compare the efficacity of isatuximab when combined to carfilzomib and dexamethasone versus carfilzomib and dexamethasone in ...

5. sanofi.com sanofi.com/en/media-room/press-releases/2023/2023-12-11-00-31-04-2793482

Sarclisa® (isatuximab) plus KRd significantly improved rate ... The Phase 3 trial investigating Sarclisa (isatuximab) in combination with carfilzomib, lenalidomide and dexamethasone (KRd) showed a statistically significant ...

6. kyprolis-hcp.com kyprolis-hcp.com/combinations/isa-kd-safety

Isa-Kd Safety | KYPROLIS® (carfilzomib) The most frequent serious adverse reactions in > 5% of patients who received Isa-Kd were pneumonia (25%) and upper respiratory tract infections (9%).