Elranatamab + Isatuximab for Multiple Myeloma

Recruiting at 1 trial location

Overseen By Noopur Raje, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must be taking: Immunomodulatory drugs, Proteasome inhibitors

Must not be taking: Investigational agents

Disqualifiers: Active infections, Cardiovascular diseases, 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: 1

Duration: Variable (until disease progression or withdrawal)

30 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, you cannot have had myeloma therapy or investigational drugs within 2 weeks before starting the trial treatment.

What data supports the effectiveness of the drug combination Elranatamab + Isatuximab for Multiple Myeloma?

Research shows that isatuximab, when combined with other drugs, improves survival and response rates in patients with multiple myeloma, suggesting it could be effective in combination with elranatamab as well. ^{1 2 3 4 5}

How is the drug combination of Elranatamab and Isatuximab unique for treating multiple myeloma?

The combination of Elranatamab and Isatuximab is unique because it involves two monoclonal antibodies, which are designed to target specific proteins on cancer cells, potentially offering a more targeted approach compared to traditional chemotherapy. Isatuximab targets the CD38 protein on multiple myeloma cells, and when combined with other treatments, it has shown improved outcomes in patients with relapsed or refractory multiple myeloma. ^{3 5 6 7 8}

What is the purpose of this trial?

This is an open-label phase 2 study of elranatamab in combination with isatuximab administered subcutaneously in patients with relapsed and refractory multiple myeloma (RRMM) who have received at least two prior lines of therapy and who have had previous treatment with both immunomodulatory drugs (IMiDs) and a proteasome inhibitor (PI). The subcutaneous injection method of isatuximab administration, including the device used to administer isatuximab, is investigational.

Research Team

Noopur Raje, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for people with multiple myeloma that has come back or didn't respond to treatment. They must have tried at least two other treatments before, including IMiDs and PIs. It's not suitable for those who can't receive subcutaneous injections or have conditions that the study doesn't allow.

Inclusion Criteria

I can take care of myself but might not be able to do heavy physical work.

I have another cancer that won't affect this treatment.

Ability to understand and sign a written informed consent document

Exclusion Criteria

I haven't had heart problems or diseases in the last 6 months.

I have been treated with a BCMA-targeted therapy before.

Participants receiving any investigational agents currently

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive elranatamab and isatuximab subcutaneously in 28-day cycles until disease progression, unacceptable toxicity, or withdrawal

Variable (until disease progression or withdrawal)

Cycle 1: Days 1, 4, 8, 15, 22; Cycles 2-6: Days 1 and 15; Cycles 7+: Day 1

Follow-up

Participants are monitored for safety and effectiveness every 3 months for 5 years after their final dose

5 years

Treatment Details

Interventions

• elranatamab
• Isatuximab

Trial Overview The study tests a combination of two drugs: elranatamab and isatuximab, given under the skin (subcutaneously) to treat relapsed/refractory multiple myeloma. The way isatuximab is given in this trial is new and being researched.

Participant Groups

Group I: Elranatamab + Isatuximab-irfc Experimental Treatment 3 Interventions

Elranatamab will be administered via subcutaneous (SC) injection usually into the abdomen or lower stomach at the following visits during each 28-day cycle: * Cycle 1: Days 1, 4, 8, 15, 22 * Cycles 2-6: Days 1 and 15 * Cycles 7+: Day 1. Isatuximab for SC administration will be administered via subcutaneous (SC) injection usually into the abdomen or lower stomach, using an investigational injector device called the on-body delivery system at the following visits during each 28-day cycle: * Cycles 2-6: Days 1 and 15 * Cycles 7+: Day 1 This will continue as long as the participant is receiving treatment.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

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

In a subgroup analysis of 36 East Asian patients with relapsed/refractory multiple myeloma, the combination of isatuximab, pomalidomide, and dexamethasone (Isa-Pd) showed improved progression-free survival compared to pomalidomide and dexamethasone alone, with a median progression-free survival not reached in the Isa-Pd group versus 7.9 months in the Pd group.

The safety profile of Isa-Pd in East Asian patients was consistent with the overall population, although a higher incidence of Grade ≥ 3 neutropenia was observed, indicating that while the treatment is effective, monitoring for this side effect is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab-Pomalidomide-Dexamethasone Versus Pomalidomide-Dexamethasone in East Asian Patients With Relapsed/Refractory Multiple Myeloma: ICARIA-MM Subgroup Analysis. Sunami, K., Ikeda, T., Huang, SY., et al.[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 involving 660 patients with newly diagnosed multiple myeloma, the addition of isatuximab to standard treatment (lenalidomide, bortezomib, and dexamethasone) significantly improved the rate of minimal residual disease (MRD) negativity, with 50% of patients in the isatuximab group achieving MRD negativity compared to 36% in the control group.

The safety profile of isatuximab was consistent with existing treatments, showing no new safety concerns, although higher rates of grade 3 or 4 neutropenia were observed in the isatuximab group (23% vs. 7% in the control group).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of isatuximab to lenalidomide, bortezomib, and dexamethasone as induction therapy for newly diagnosed, transplantation-eligible patients with multiple myeloma (GMMG-HD7): part 1 of an open-label, multicentre, randomised, active-controlled, phase 3 trial. Goldschmidt, H., Mai, EK., Bertsch, U., et al.[2022]

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]

Isatuximab (anti-CD38) and F50067 (anti-CXCR4) showed promising results as monotherapies in treating multiple myeloma, with overall response rates of 66.7% and 32%, respectively, based on a review of 39 studies involving 1906 patients.

Combination therapies using Isatuximab with lenalidomide and dexamethasone achieved a clinical benefit rate of 83%, while Indatuximab Ravtansine showed response rates of 78% and 79% when combined with these agents, indicating that mAbs can enhance treatment efficacy when used alongside traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigational Monoclonal Antibodies in the Treatment of Multiple Myeloma: A Systematic Review of Agents under Clinical Development. Iftikhar, A., Hassan, H., Iftikhar, N., et al.[2023]

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]

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]

References

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

Isatuximab for relapsed/refractory multiple myeloma: review of key subgroup analyses from the Phase III ICARIA-MM study. [2022]

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

Isatuximab-Pomalidomide-Dexamethasone Versus Pomalidomide-Dexamethasone in East Asian Patients With Relapsed/Refractory Multiple Myeloma: ICARIA-MM Subgroup Analysis. [2022]

3. 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]

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

Addition of isatuximab to lenalidomide, bortezomib, and dexamethasone as induction therapy for newly diagnosed, transplantation-eligible patients with multiple myeloma (GMMG-HD7): part 1 of an open-label, multicentre, randomised, active-controlled, phase 3 trial. [2022]

5. France pubmed.ncbi.nlm.nih.gov

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

6. Switzerland pubmed.ncbi.nlm.nih.gov

Investigational Monoclonal Antibodies in the Treatment of Multiple Myeloma: A Systematic Review of Agents under Clinical Development. [2023]

7. 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]

8. England pubmed.ncbi.nlm.nih.gov

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