Elotuzumab + Iberdomide + Dexamethasone for Multiple Myeloma

Recruiting at 2 trial locations

Overseen by Omar Nadeem, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Omar Nadeem, MD

Must not be taking: CYP3A inducers, CYP1A2 inhibitors

Disqualifiers: Prior Iberdomide, Other malignancy, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

The aim of this research study is to evaluate the efficacy of Elotuzumab and Iberdomide therapy post-Idecabtagene Vicleucel in participants with relapsed and refractory multiple myeloma. The names of the study drugs involved in this study are: * Iberdomide (a type of cereblon E3 ligase modulator) * Elotuzumab (a type of monoclonal antibody) * Dexamethasone (a type of steroid)

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have certain treatments like strong CYP3A inducers or inhibitors within 14 days before starting the trial, and you should not have had certain other therapies within specific time frames before the trial begins.

What data supports the effectiveness of the drug combination Elotuzumab, Iberdomide, and Dexamethasone for treating multiple myeloma?

Research shows that Iberdomide combined with Dexamethasone has shown promising results in treating heavily pretreated multiple myeloma, and Elotuzumab combined with other drugs like Pomalidomide and Dexamethasone has improved survival in similar conditions. These findings suggest that the combination of Elotuzumab, Iberdomide, and Dexamethasone could be effective for multiple myeloma. ^{1 2 3 4 5}

Is the combination of Elotuzumab, Iberdomide, and Dexamethasone safe for humans?

Studies show that Elotuzumab and Dexamethasone, when used together, do not add significant toxicity compared to other treatments. Iberdomide with Dexamethasone has been evaluated for safety in heavily pretreated multiple myeloma patients, but specific safety data for the combination with Elotuzumab is not detailed in the available research. ^{2 5 6 7 8}

What makes the drug combination of Elotuzumab, Iberdomide, and Dexamethasone unique for treating multiple myeloma?

This drug combination is unique because Iberdomide is a new type of drug that enhances the immune system and works well with other treatments like dexamethasone, while Elotuzumab is an antibody that helps the immune system target cancer cells. Together, they offer a novel approach by combining immune-stimulating effects with direct cancer cell targeting, which may improve outcomes for patients with relapsed or resistant multiple myeloma. ^{1 2 3 4 9}

Research Team

Omar Nadeem, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for individuals with relapsed and refractory multiple myeloma who have previously undergone Idecabtagene Vicleucel therapy. Participants should meet specific health criteria to be eligible.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document

All participants must agree to specific restrictions regarding blood and semen donation

I received ide-cel treatment, responded well, and it's been less than 90 days since my infusion.

Exclusion Criteria

Known seropositive for active viral infection with specified viruses

Participants receiving any other investigational agents for any indication

I take more than the specified amount of corticosteroids.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1: Dose Escalation

Participants receive Iberdomide, Elotuzumab, and Dexamethasone in a 3+3 dose escalation design to find the Maximum Tolerated Dose

8 weeks

Weekly visits for drug administration and monitoring

Treatment Phase 2: Dose Expansion

Participants receive Iberdomide, Elotuzumab, and Dexamethasone at the determined dose level

Until disease progression or unacceptable toxicity

Weekly visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 28 days for up to 2 years

Monthly visits

Treatment Details

Interventions

• Dexamethasone (Corticosteroid)
• Elotuzumab (Monoclonal Antibodies)
• Iberdomide (Other)

Trial Overview The study tests the effectiveness of combining Elotuzumab (monoclonal antibody) and Iberdomide (cereblon E3 ligase modulator) with Dexamethasone (steroid) in patients post-Ide-cel treatment for multiple myeloma.

Participant Groups

Group I: Phase 2: Dose Expansion Experimental Treatment 3 Interventions

Participants will be enrolled and will complete study procedures as follows: * Baseline visit * Cycle 1 through Cycle 2: * Days 1 through 21 of 28 Day Cycle: Predetermined dose of Iberdomide 1x daily. * Days 1, 8, 15, and 22 of 28 Day Cycle: Predetermined dose of Dexamethasone 1x daily. * Days 1, 8, 15, and 22 of 23 Day Cycle: Predetermined dose of Elotuzumab 1x daily. * Cycle 3 through End of Treatment: * Days 1 through 21 of 28 Day Cycle: Predetermined dose of Iberdomide 1x daily. * Day 1 of 28 Day Cycle: Predetermined dose of Dexamethasone 1x daily. * Days 1, 8, 15, and 22 of 23 Day Cycle: Predetermined dose of Elotuzumab 1x daily. * End of Treatment visit * 14 Day Follow Up Visit: to be in-clinic after end of treatment visit. * Follow Up: Every 28 days for up to 2 years

Group II: Phase 1: Dose Escalation Experimental Treatment 3 Interventions

Participants will be enrolled in a standard 3+3 dose escalation design to find the Maximum Tolerated Dose (MTD) of Iberdomide, starting at Dose Level 0 and increasing to Dose Level 1 * Baseline visit * Cycle 1 through Cycle 2: * Days 1 through 21 of 28 Day Cycle: Predetermined dose of Iberdomide 1x daily * Days 1, 8, 15, and 22 of 28 Day Cycle: Predetermined dose of Dexamethasone 1x daily * Days 1, 8, 15, and 22 of 28 Day Cycle: Predetermined dose of Elotuzumab 1x daily * Cycle 3 through End of Treatment: * Days 1 through 21 of 28 Day Cycle: Predetermined dose of Iberdomide 1x daily * Day 1 of 28 Day Cycle: Predetermined dose of Dexamethasone 1x daily * Day 1 of 28 Day Cycle: Predetermined dose of Elotuzumab 1x daily * End of Treatment visit * 14 Day Follow Up Visit: to be in-clinic after end of treatment visit * Follow Up: Every 28 days for up to 2 years * Dose expansion will proceed according to dose-limiting toxicity (DLT) guidelines per the protocol

Who Is Running the Clinical Trial?

Omar Nadeem, MD

Lead Sponsor

Trials

3

Recruited

160+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Celgene

Industry Sponsor

Trials

649

Recruited

130,000+

Top Products

>- **Revlimid (lenalidomide)**: Multiple myeloma, myelodysplastic syndromes, and mantle cell lymphoma treatment. - **Pomalyst (pomalidomide)**: Relapsed/refractory multiple myeloma treatment. - **Otezla (apremilast)**: Psoriatic arthritis treatment. - **Thalomid (thalidomide)**: Erythema nodosum leprosum and multiple myeloma treatment.

Jay Backstrom

Celgene

Chief Medical Officer since 2016

MD

Mark Alles

Celgene

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Findings from Research

In the phase II ELOQUENT-3 trial, the combination of elotuzumab with pomalidomide and dexamethasone (EPd) significantly improved overall survival (OS) in patients with relapsed/refractory multiple myeloma, with a median OS of 29.8 months compared to 17.4 months for the pomalidomide/dexamethasone (Pd) group.

The safety profile of EPd was consistent with previous studies, showing no new safety concerns, indicating that this treatment is both effective and safe for patients who have already undergone multiple lines of therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elotuzumab Plus Pomalidomide and Dexamethasone for Relapsed/Refractory Multiple Myeloma: Final Overall Survival Analysis From the Randomized Phase II ELOQUENT-3 Trial. Dimopoulos, MA., Dytfeld, D., Grosicki, S., et al.[2023]

Iberdomide combined with dexamethasone demonstrated meaningful clinical activity in heavily pretreated patients with relapsed or refractory multiple myeloma, achieving an overall response rate of 32% in the dose-escalation cohort and 26% in the dose-expansion cohort, indicating its potential effectiveness even in difficult-to-treat cases.

The treatment was generally safe, with a recommended phase 2 dose established at 1.6 mg, although some patients experienced serious adverse events, including neutropenia and infections, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iberdomide plus dexamethasone in heavily pretreated late-line relapsed or refractory multiple myeloma (CC-220-MM-001): a multicentre, multicohort, open-label, phase 1/2 trial. Lonial, S., Popat, R., Hulin, C., et al.[2022]

In a study of 117 patients with relapsed or refractory multiple myeloma, those treated with elotuzumab plus pomalidomide and dexamethasone experienced a median progression-free survival of 10.3 months, compared to 4.7 months for those receiving pomalidomide and dexamethasone alone, indicating a significant improvement in treatment efficacy.

The overall response rate was also higher in the elotuzumab group at 53% versus 26% in the control group, with fewer severe adverse events like neutropenia and anemia, suggesting that elotuzumab may enhance treatment outcomes while maintaining a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elotuzumab plus Pomalidomide and Dexamethasone for Multiple Myeloma. Dimopoulos, MA., Dytfeld, D., Grosicki, S., et al.[2019]

Elotuzumab, a humanized monoclonal antibody targeting SLAMF7, has been shown to enhance the effectiveness of treatments for relapsed and/or refractory multiple myeloma when combined with lenalidomide/dexamethasone or pomalidomide/dexamethasone, leading to FDA approval for these combinations.

The use of elotuzumab stimulates natural killer cells to attack multiple myeloma cells, offering a promising mechanism of action that could improve treatment outcomes without significantly increasing toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elotuzumab in the treatment of relapsed and refractory multiple myeloma. Grosicki, S., Bednarczyk, M., Barchnicka, A., et al.[2021]

In a study of 22 patients with relapsed or refractory multiple myeloma, the combination of bortezomib and dexamethasone (BD therapy) resulted in a high response rate, with 77.3% achieving at least a partial response, indicating its efficacy.

Switching to a once-weekly administration of bortezomib after initial twice-weekly treatment significantly reduced severe gastrointestinal side effects while maintaining the therapy's effectiveness, suggesting a safer dosing strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of bortezomib plus dexamethasone therapy for refractory or relapsed multiple myeloma: once-weekly administration of bortezomib may reduce the incidence of gastrointestinal adverse events. Fukushima, T., Nakamura, T., Iwao, H., et al.[2015]

Ibrutinib, a novel oral treatment for multiple myeloma, showed a clinical benefit rate of 28% when combined with low-dose dexamethasone in patients who had undergone a median of 4 prior therapies, indicating its potential effectiveness in relapsed/refractory cases.

The study reported manageable safety profiles, with grade 3-4 adverse events occurring in a minority of patients, suggesting that ibrutinib could be a tolerable option for patients with multiple myeloma who have limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib alone or with dexamethasone for relapsed or relapsed and refractory multiple myeloma: phase 2 trial results. Richardson, PG., Bensinger, WI., Huff, CA., et al.[2021]

In a study of 23 patients with relapsed or refractory multiple myeloma, both low (1.0 mg/m2) and standard (1.3 mg/m2) doses of bortezomib combined with dexamethasone showed similar response rates, with 70% for the low dose and 61.5% for the standard dose, indicating that lower doses can be just as effective.

However, the standard dose of 1.3 mg/m2 was associated with more adverse effects, including serious infections and treatment-related deaths, suggesting that while it may be more effective, it also carries a higher risk of toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effects of bortezomib at different doses in combination with dexamethasone in treatment of relapsed or refractory multiple myeloma: a comparative study]. Bao, L., Lu, XJ., Zhang, XH., et al.[2015]

In a phase 2 study involving 152 patients with relapsed/refractory multiple myeloma, the combination of elotuzumab with bortezomib and dexamethasone (EBd) resulted in a longer progression-free survival (PFS) of 9.7 months compared to 6.9 months with bortezomib and dexamethasone alone (Bd).

The addition of elotuzumab did not increase clinically significant adverse events, indicating that it can provide clinical benefits without added toxicity, and it showed a promising overall response rate of 66% compared to 63% for Bd.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase 2 study: elotuzumab plus bortezomib/dexamethasone vs bortezomib/dexamethasone for relapsed/refractory MM. Jakubowiak, A., Offidani, M., Pégourie, B., et al.[2022]

Elotuzumab, a monoclonal antibody targeting the SLAMF7 receptor, shows significant antimyeloma activity when combined with other treatments like bortezomib or lenalidomide, improving patient responses without adding extra toxicity.

Approved by the FDA in 2015 for patients with relapsed or refractory multiple myeloma after 1-3 prior therapies, elotuzumab has demonstrated efficacy in clinical trials, particularly in combination therapies, while showing a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of elotuzumab for the treatment of multiple myeloma. Gavriatopoulou, M., Terpos, E., Kastritis, E., et al.[2018]

References

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

Elotuzumab Plus Pomalidomide and Dexamethasone for Relapsed/Refractory Multiple Myeloma: Final Overall Survival Analysis From the Randomized Phase II ELOQUENT-3 Trial. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Iberdomide plus dexamethasone in heavily pretreated late-line relapsed or refractory multiple myeloma (CC-220-MM-001): a multicentre, multicohort, open-label, phase 1/2 trial. [2022]

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

Elotuzumab plus Pomalidomide and Dexamethasone for Multiple Myeloma. [2019]

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

Elotuzumab in the treatment of relapsed and refractory multiple myeloma. [2021]

5. Greece pubmed.ncbi.nlm.nih.gov

Efficacy and safety of bortezomib plus dexamethasone therapy for refractory or relapsed multiple myeloma: once-weekly administration of bortezomib may reduce the incidence of gastrointestinal adverse events. [2015]

6. England pubmed.ncbi.nlm.nih.gov

Ibrutinib alone or with dexamethasone for relapsed or relapsed and refractory multiple myeloma: phase 2 trial results. [2021]

7. China pubmed.ncbi.nlm.nih.gov

[Effects of bortezomib at different doses in combination with dexamethasone in treatment of relapsed or refractory multiple myeloma: a comparative study]. [2015]

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

Randomized phase 2 study: elotuzumab plus bortezomib/dexamethasone vs bortezomib/dexamethasone for relapsed/refractory MM. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of elotuzumab for the treatment of multiple myeloma. [2018]