Elranatamab + Isatuximab for Multiple Myeloma

Not yet 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)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments, elranatamab and isatuximab, for individuals with multiple myeloma, a type of blood cancer that has returned or not responded to treatment. The goal is to assess the effectiveness of these drugs when administered together as subcutaneous injections. It targets those who have tried at least two other treatments, including specific immune and protein-targeted therapies. Individuals who have undergone multiple myeloma treatments and seek new options might be suitable candidates. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that combining elranatamab and isatuximab may help treat multiple myeloma, but safety remains a top priority. Studies have found that elranatamab can cause side effects, with blood-related issues occurring in about 83.8% of patients. Infections were reported in about 70.3% of patients.

When used with other drugs, isatuximab hasn't shown major improvements in survival rates, but its safety is generally manageable. Patients should be aware of these possible side effects and discuss them with their doctor.

This treatment is currently being tested in a phase 2 trial. At this stage, some evidence of safety exists, but more research is needed to fully understand how well patients handle the combination. Always consult a healthcare professional before joining any clinical trial to understand the potential risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Elranatamab combined with Isatuximab for multiple myeloma because of their novel approach to treatment. Unlike standard therapies, Elranatamab is a bispecific antibody that targets both BCMA on myeloma cells and CD3 on T-cells, which helps the immune system directly attack cancer cells. Additionally, both drugs are administered subcutaneously, offering a more convenient and potentially less invasive option compared to traditional intravenous infusions. This unique combination targets multiple pathways in cancer cells, which may enhance effectiveness and provide new hope for patients who have exhausted other options.

What evidence suggests that the combination of elranatamab and isatuximab could be effective for multiple myeloma?

This trial will evaluate the combination of elranatamab and isatuximab for treating multiple myeloma. Studies have shown that using these two drugs together looks promising, especially when other treatments have failed. Research indicates that elranatamab alone improves the condition in 91.9% of patients, while isatuximab alone has a 66.7% success rate. Together, these treatments target different parts of the cancer cells, potentially increasing their effectiveness. Early data on similar combinations have shown a 97.3% success rate, suggesting strong potential. These findings offer hope for those with relapsed and hard-to-treat multiple myeloma. ^{1 5 6 7 8}

Who Is on the Research Team?

Noopur Raje, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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]

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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06832865

NCT06832865 | ELISA in Relapsed/Refractory MM This research is being done to see if the study drugs, elranatamab and isatuximab-irfc, reduce the risk of worsening disease and to evaluate the possible risks ...

2. withpower.com withpower.com/trial/elranatamab-isatuximab-for-multiple-myeloma-4e573

Elranatamab + Isatuximab for Multiple Myeloma Isatuximab (anti-CD38) and F50067 (anti-CXCR4) showed promising results as monotherapies in treating multiple myeloma, with overall response rates of 66.7% and ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11992987/

Economic Impact of Elranatamab for Treatment of Patients ... Elranatamab for RRMM is projected to result in a minimal to small budget impact over 3 years and good economic value with lower cost of care per month of PFS.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0268960X25000876

Bispecific antibodies in multiple myeloma Early results show a high response rate of 91.9 % and an manageable safety profile [68]. In transplant-eligible patients, more mature data was ...

5. bloodcancerstoday.com bloodcancerstoday.com/post/new-study-support-for-bispecific-antibodies-in-combinations-for-newly-diagnosed-multiple-myeloma

New Study Support for Bispecific Antibodies in ... Regarding initial data on response at a median follow-up of 7.9 months, the objective response rate (ORR) was 97.3%. Dr. Trudel noted that this ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2023/761345Orig1s000MultidisciplineR.pdf

761345Orig1s000 - accessdata.fda.gov Overall, the efficacy, safety, and PD data support the proposed elranatamab dosing regimen for ... Outcomes of patients with multiple myeloma ...

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

Efficacy and Safety of Isatuximab Combination Therapy in ... In NDMM patients, no significant OS benefit was observed with isatuximab (HR = 1.01, 95% CI: 0.72–1.43, p = 0.937), likely reflecting the immaturity of survival ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10579053/

Elranatamab in relapsed or refractory multiple myeloma Even after prior BCMA-directed therapy, 53.8% achieved response. For all 55 patients, median PFS was 11.8 months, and median OS was 21.2 months.