Iberdomide + Elotuzumab + Dexamethasone for Multiple Myeloma

(CC-220 Trial)

Overseen By Donna Catamero, MSH

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Icahn School of Medicine at Mount Sinai

Must not be taking: Strong CYP3A inhibitors

Disqualifiers: Plasmacytoma, Plasma cell leukemia, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for multiple myeloma, a type of blood cancer. It combines three drugs: Iberdomide (an experimental treatment), Elotuzumab, and Dexamethasone, to determine their effectiveness in killing cancer cells and their safety for patients. The goal is to find the best dose that patients can tolerate. Individuals with multiple myeloma that has returned or is not responding to previous treatments might be suitable for this trial. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

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

The trial requires that you stop any anti-myeloma drug therapy within 14 days before starting the study treatment and any experimental drug therapy within 28 days. Additionally, you must not have taken melphalan within 4 weeks or corticosteroids (other than Dexamethasone) within 3 weeks before the first dose of the study drug.

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

Research has shown that combining Iberdomide with Elotuzumab and Dexamethasone might be safe and manageable for patients with relapsed or refractory multiple myeloma (RRMM). This trial is in its early stages, meaning the treatment is just beginning to be tested in people to assess its initial safety.

Previous studies have found that Iberdomide is generally well-tolerated when used with other drugs. Elotuzumab and Dexamethasone are already used together to treat multiple myeloma, so their safety is well-established. Early results suggest that adding Iberdomide might not cause many additional side effects.

However, since the treatment is still under investigation, potential participants should know that the complete safety details are not yet fully understood. It is important to consult a healthcare provider with any questions about joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of Iberdomide, Elotuzumab, and Dexamethasone for treating Multiple Myeloma because it represents a novel approach in tackling this type of cancer. Unlike standard treatments such as proteasome inhibitors or immunomodulatory drugs, Iberdomide is a new cereblon modulator, potentially offering a fresh mechanism of action by enhancing the immune response against cancer cells. Elotuzumab, an antibody, works synergistically with Iberdomide to target and destroy myeloma cells more effectively. This combination aims to improve patient outcomes by leveraging these distinct mechanisms to attack the cancer from multiple angles.

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

Research has shown that combining iberdomide with dexamethasone holds promise for treating multiple myeloma, especially in patients who have tried other treatments. Studies have found that elotuzumab, when used with dexamethasone, activates immune cells to target and destroy myeloma cells. In this trial, participants will receive a combination of iberdomide, elotuzumab, and dexamethasone, which is believed to work well together by strengthening the immune system while directly attacking cancer cells. Early results suggest this combination might significantly reduce tumors in multiple myeloma patients. This approach relies on the idea that these drugs can enhance each other's effects. ^{1 3 6 7 8}

Who Is on the Research Team?

Samir Parekh

Principal Investigator

Icahn school of medicine

Cesar Rodriguez, MD

Principal Investigator

Icahn School of Medicine

Are You a Good Fit for This Trial?

Adults with relapsed/refractory multiple myeloma who have had 1-3 prior treatments including specific therapies (IMiD, proteasome inhibitor, anti-CD38 agent) can join. They must not be pregnant or breastfeeding and agree to use contraception. Excluded are those with certain other medical conditions, recent surgeries, active infections requiring long-term treatment, or previous Iberdomide/Elotuzumab use.

Inclusion Criteria

You have more than 200 milligrams of M-protein in your urine in a 24-hour sample.

Before joining the study, you must have a disease that can be measured or seen on tests.

You have high levels of M-protein in your blood.

Exclusion Criteria

I haven't had major heart surgery in the last 8 weeks or any other major surgery in the last 4 weeks.

You had a very bad allergic reaction to a medication called IMiD in the past.

Your liver enzymes are more than three times the normal level.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Finding

Open-label, sequential allocation, dose-finding evaluation of Iberdomide in combination with Elotuzumab and Dexamethasone to determine the maximum tolerated dose

28 days

Dose-Expansion

Open-label, single-arm dose expansion cohort to verify safety and tolerability and examine anti-myeloma activity at the maximum tolerated dose

up to 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dexamethasone
• Elotuzumab
• Iberdomide

Trial Overview The trial tests a combination of Iberdomide (CC-220), Elotuzumab, and Dexamethasone in patients whose multiple myeloma has returned after treatment. It's an open-label study where everyone gets the same drugs but at different doses to find the highest dose that's safe (MTD). Up to 37 people will participate.

How Is the Trial Designed?

Group I: Iberdomide, Elotuzumab and Dexamethasone Experimental Treatment 3 Interventions

Dose-Finding: Patients will be enrolled in a 3+3 dose escalation cohort. Dose-Expansion: additionally enrolled patients at the recommended maximum tolerated dose of Iberdomide as was determined in Part 1 (Dose-Finding Phase).

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

Approved in European Union as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases
• Immune system disorders

Approved in United States as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders
• Neoplastic diseases
• Nervous system disorders

Approved in Canada as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases

Approved in Japan as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Multiple Myeloma Research Consortium

Collaborator

Trials

21

Recruited

1,200+

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

Published Research Related to This Trial

In the phase III ELOQUENT-2 trial involving adults with relapsed multiple myeloma, elotuzumab combined with lenalidomide and dexamethasone significantly improved progression-free survival and overall response rates compared to the standard treatment alone.

The addition of elotuzumab did not negatively affect health-related quality of life and had a manageable safety profile, with the most common serious side effects being blood-related issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elotuzumab: A Review in Relapsed and/or Refractory Multiple Myeloma. Lamb, YN.[2019]

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]

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]

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 involving 98 relapsed refractory multiple myeloma patients, treatment with lenalidomide plus dexamethasone resulted in a 52% overall response rate, with 49% achieving partial remission and 3% achieving complete remission, despite patients having undergone a median of 5 prior treatments.

The combination therapy not only provided rapid responses but also extended overall survival by nearly six months, demonstrating its efficacy and safety regardless of previous treatments with thalidomide and bortezomib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in relapsed refractory myeloma patients: impact of previous response to bortezomib and thalidomide on treatment efficacy. Results of a medical need program in Belgium. Delforge, M., Michiels, A., Doyen, C., et al.[2018]

In a phase 1/2 trial involving 65 patients with newly diagnosed multiple myeloma, the combination of oral ixazomib, lenalidomide, and dexamethasone was found to be generally well tolerated, with a maximum tolerated dose of ixazomib established at 2.97 mg/m².

The treatment resulted in a very good partial response or better in 58% of patients, indicating significant efficacy and supporting further phase 3 trials for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of ixazomib, an oral proteasome inhibitor, in combination with lenalidomide and dexamethasone in patients with previously untreated multiple myeloma: an open-label phase 1/2 study. Kumar, SK., Berdeja, JG., Niesvizky, R., et al.[2019]

Both high-dose and low-dose dexamethasone combined with bortezomib and thalidomide significantly improved the overall remission rate in 96 patients with multiple myeloma compared to a placebo, with no significant difference in efficacy between the two dexamethasone doses.

The low-dose dexamethasone regimen resulted in fewer adverse reactions, such as fatigue and peripheral neuropathy, indicating better safety while maintaining similar therapeutic benefits as the high-dose regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Efficacy and Safety of Different Doses of Dexamethasone Combined with Bortezomib and Thalidomide for Treating Patients with Multiple Myeloma]. Li, CS., Ji, Y., Zhang, WP., et al.[2018]

Lenalidomide combined with dexamethasone has been shown to be effective for treating relapsed/refractory multiple myeloma, and it has received approval from both the FDA and EMA for patients who have undergone at least one prior therapy.

The most common serious side effects include cytopenias and infections, but an expert panel has provided management strategies to minimize these risks, ensuring that patients can receive the full benefits of the treatment without unnecessary dose reductions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma. Palumbo, A., Dimopoulos, M., San Miguel, J., et al.[2018]

Elotuzumab, when combined with lenalidomide and dexamethasone, significantly improves progression-free survival (PFS) in patients with relapsed or refractory multiple myeloma, with a median PFS of 19.4 months compared to 14.9 months for the standard treatment.

The treatment showed a higher overall response rate (ORR) of 75.8% versus 65.5% for the standard therapy, although serious adverse reactions were more common in the elotuzumab group (65% vs. 57%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Drug Approval: Elotuzumab in Combination with Lenalidomide and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma. Gormley, NJ., Ko, CW., Deisseroth, A., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05560399

NCT05560399 | A Study of Iberdomide (CC-220) in ... This is a single-arm, open-label study evaluating the safety, tolerability and efficacy of Iberdomide (CC-220) in combination with Elotuzumab and ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05560399?term=CC-220&cond=multiple%20myeloma&viewType=Table&rank=2

A Study of Iberdomide ( CC-220 ) in Combination With ... Members are chosen based on the scientific skills and knowledge needed to monitor the particular trial. Also called a data safety and monitoring board, or DSMB.

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/6860/528880/Elotuzumab-Iberdomide-Dexamethasone-Combination

Elotuzumab-Iberdomide-Dexamethasone Combination ... Elotuzumab-Iberdomide-Dexamethasone Combination Therapy Activates T and NK Cells within the Immune Microenvironment of Multiple Myeloma Patients ...

4. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/iberdomide?pn=1

Clinical Trials Using Iberdomide - NCI Clinical Trials Using Iberdomide. Review the clinical trials studying iberdomide on this list and use the filters to refine the results by age and location.

5. withpower.com withpower.com/trial/early-phase-1-neoplasms-plasma-cell-9-2022-15706

Iberdomide + Elotuzumab + Dexamethasone for Multiple ... Research shows that Iberdomide combined with Dexamethasone has shown promising results in treating heavily pretreated multiple myeloma, and Elotuzumab combined ...

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-09279

Iberdomide, Elotuzumab, and Dexamethasone for the ... Giving iberdomide in combination with elotuzumab and dexamethasone may be safe, tolerable, and/or effective in treating patients with relapsed or refractory ...

7. myeloma.org myeloma.org/treatment/multiple-myeloma-medications/iberdomide

Iberdomide Iberdomide is a CELMoD agent that is being studied in many clinical trials with different drug combinations and in different myeloma patient populations.

8. dana-farber.org dana-farber.org/clinical-trials/24-189

A Phase I/II Study of Elotuzumab and Iberdomide ... The aim of this research study is to evaluate the efficacy of Elotuzumab and Iberdomide therapy post-Idecabtagene Vicleucel in participants with relapsed ...