Iberdomide + Daratumumab for Multiple Myeloma

(IBEX Trial)

Recruiting at 1 trial location

Overseen By Jeffrey Zonder

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Barbara Ann Karmanos Cancer Institute

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: HIV, Hepatitis B, Heart attack, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 4

Duration: 24 months

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, Iberdomide and Daratumumab (a monoclonal antibody therapy), to determine their effectiveness for people with Multiple Myeloma who have residual disease after a stem cell transplant. The main goals are to assess whether these treatments reduce residual cancer cells and ensure their safety for ongoing use. Suitable candidates have undergone a stem cell transplant, experienced some success with previous treatment, but still show detectable cancer activity. Participants will receive regular health checks and testing to monitor the treatment's effects. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group, offering participants a chance to potentially benefit from innovative therapies.

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 use strong inhibitors or inducers of certain enzymes (CYP3A4, P-gp, or BCRP) for at least 14 days 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 Iberdomide and Daratumumab is generally safe for people with multiple myeloma. Studies have found that patients tolerate these drugs well, with most experiencing manageable side effects. This suggests the treatment does not cause unexpected or severe harm to most patients. It is important to consult a healthcare provider for details specific to individual health situations. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Iberdomide and Daratumumab because they offer a novel approach to treating multiple myeloma. Unlike traditional treatments, which often focus on broadly targeting cancer cells, Iberdomide is an oral drug that modulates the immune system to enhance its ability to fight cancer. Daratumumab works by targeting CD38, a protein highly expressed on myeloma cells, to help the immune system better identify and attack these cells. This combination aims to not only target the cancer directly but also harness the body’s immune response, potentially leading to more effective and sustained outcomes for patients.

What evidence suggests that Iberdomide and Daratumumab could be effective for Multiple Myeloma?

Previous studies have shown that the combination of iberdomide and daratumumab holds promise for treating multiple myeloma. Specifically, research indicates that this combination achieved a 93.1% overall response rate, meaning most patients saw their cancer respond well. Additionally, the treatment improved rates of minimal residual disease negativity, reducing the small amounts of cancer left after initial treatments. This trial will evaluate the effectiveness of the iberdomide and daratumumab combination, which could help manage multiple myeloma, especially for those with remaining disease after initial therapy. ^{1 2 3 4 6}

Who Is on the Research Team?

Jeffrey Zonder, M.D.

Principal Investigator

Barbara Ann Karmanos Cancer Institute

Are You a Good Fit for This Trial?

This trial is for Multiple Myeloma patients who've had prior therapy with Daratumumab, responded at least partially, completed an Autologous Stem Cell Transplant (ASCT) within the last 90-150 days without progression, and are Minimal Residual Disease positive. They must be physically able to perform daily activities with minimal assistance (ECOG Performance Status ≤2), have adequate bone marrow function and organ function.

Inclusion Criteria

I finished my stem cell transplant 3-5 months ago, haven't had treatment since, and my condition hasn't worsened.

I finished my stem cell transplant 3-5 months ago and haven't had treatment or disease progression since.

My cancer is detectable at a very low level in my blood or bone marrow.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive Iberdomide and SC Daratumumab as maintenance therapy post-ASCT, with dose adjustments based on tolerance, for up to 26 cycles or until disease progression

24 months

Multiple visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including MRD assessments at 6, 12, and 24 months

24 months

3 visits (in-person) for MRD assessment

What Are the Treatments Tested in This Trial?

Interventions

• Daratumumab
• Iberdomide

Trial Overview The trial tests if Iberdomide combined with subcutaneous Daratumumab can effectively maintain remission in Multiple Myeloma patients post-ASCT. It's a phase 2 study where participants receive Iberdomide orally for three weeks of each month and Daratumumab injections weekly initially, then less frequently over up to 26 cycles unless disease progresses.

How Is the Trial Designed?

Group I: Iberdomide and Daratumumab Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

Barbara Ann Karmanos Cancer Institute

Lead Sponsor

Trials

166

Recruited

9,300+

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

Multiple Myeloma Research Consortium

Collaborator

Trials

21

Recruited

1,200+

Janssen Pharmaceuticals

Industry Sponsor

Trials

87

Recruited

208,000+

Joaquin Duato

Janssen Pharmaceuticals

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Pharmaceuticals

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

Daratumumab is a monoclonal antibody that effectively targets CD38 on multiple myeloma cells, leading to cell death through various mechanisms such as complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity.

It has shown a favorable safety profile and significant clinical activity as both a standalone treatment and in combination with lenalidomide for patients with relapsed multiple myeloma who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: monoclonal antibody therapy to treat multiple myeloma. Xia, C., Ribeiro, M., Scott, S., et al.[2018]

In a subgroup analysis of the CASTOR trial involving 498 patients, daratumumab combined with bortezomib and dexamethasone (D-Vd) significantly prolonged progression-free survival (PFS) in patients with high cytogenetic risk (12.6 months) compared to bortezomib and dexamethasone alone (6.2 months).

D-Vd also demonstrated a higher rate of minimal residual disease (MRD) negativity, indicating deeper responses in treatment effectiveness, while maintaining a safety profile consistent with the overall study population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma: subgroup analysis of CASTOR based on cytogenetic risk. Weisel, K., Spencer, A., Lentzsch, S., et al.[2021]

Daratumumab, a monoclonal antibody targeting CD38, has been approved in the USA for treating multiple myeloma in patients who have undergone at least three prior therapies, demonstrating its role as a treatment option for difficult-to-treat cases.

In a phase II trial, daratumumab monotherapy showed an overall response rate of about 30% in patients with relapsed or refractory multiple myeloma, indicating its efficacy in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: First Global Approval. McKeage, K.[2018]

Daratumumab, a monoclonal antibody targeting CD38, has shown significant efficacy as a monotherapy in relapsed/refractory multiple myeloma, achieving an overall response in about one-third of patients, with rapid and durable effects.

In combination with other treatments like bortezomib or lenalidomide, daratumumab significantly prolonged progression-free survival, although the overall survival benefit is still being evaluated, and it was generally well tolerated with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Relapsed and/or Refractory Multiple Myeloma. Blair, HA.[2018]

Intravenous daratumumab, when combined with bortezomib, thalidomide, and dexamethasone, significantly improves treatment outcomes for adults with newly diagnosed multiple myeloma, leading to higher rates of stringent complete response and prolonged progression-free survival, as shown in the phase III CASSIOPEIA trial.

The addition of daratumumab has a minimal impact on overall toxicity, with the most common serious side effects being blood-related issues, indicating it is a relatively safe option for patients undergoing treatment for multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Combination Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma. Lamb, YN.[2021]

In a study of 15 multiple myeloma patients with renal impairment, daratumumab-based treatments showed a high overall response rate of 91%, indicating strong efficacy in this patient group.

The treatment was generally safe, with the most common side effects being mild neutropenia and infusion-related reactions, suggesting that daratumumab can be a viable option for managing multiple myeloma in patients with kidney issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The Efficacy and Safety of Daratumumab-Based Regimen in Treatment of Multiple Myeloma Patients with Renal Impairment]. Yin, LL., Shen, YL., Min, FL., et al.[2023]

Intravenous daratumumab, when combined with bortezomib, melphalan, and prednisone, significantly improves progression-free survival in patients with newly diagnosed multiple myeloma who cannot undergo autologous stem cell transplantation, as shown in the phase 3 ALCYONE trial.

The addition of daratumumab does not increase overall toxicity compared to the standard treatment, although it may lead to more infusion-related reactions and infections, making it a promising and relatively safe treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Combination Therapy for Transplant-Ineligible Newly Diagnosed Multiple Myeloma. Syed, YY.[2021]

In a phase 3 study (CASTOR) with a median follow-up of 19.4 months, the combination of daratumumab, bortezomib, and dexamethasone significantly improved progression-free survival (16.7 months) compared to bortezomib and dexamethasone alone (7.1 months), indicating its efficacy in treating relapsed/refractory multiple myeloma.

Daratumumab plus bortezomib and dexamethasone also showed a higher overall response rate (83.8% vs. 63.2%) and was particularly beneficial for patients with one prior line of therapy, demonstrating a favorable safety profile consistent over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab plus bortezomib and dexamethasone versus bortezomib and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of CASTOR. Spencer, A., Lentzsch, S., Weisel, K., et al.[2019]

Citations

1. news.bms.com news.bms.com/news/corporate-financial/2025/Bristol-Myers-Squibb-Announces-Phase-3-EXCALIBER-RRMM-Study-Evaluating-Iberdomide-in-Combination-with-Standard-Therapies-Demonstrated-a-Significant-Improvement-in-Minimal-Residual-Disease-Negativity-Rates-in-Relapsed-or-Refractory-Multiple-Myeloma/default.aspx

Bristol Myers Squibb Announces Phase 3 EXCALIBER ... The safety profile of iberdomide in combination with daratumumab and dexamethasone in this study is generally consistent with previous studies.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04975997

NCT04975997 | Open-label Study Comparing Iberdomide, ... To evaluate clinical efficacy in terms of overall survival (OS) in participants with relapsed or refractory multiple myeloma (RRMM) treated with iberdomide, ...

3. onclive.com onclive.com/view/iberdomide-daratumumab-dexamethasone-is-effective-in-newly-diagnosed-multiple-myeloma

Iberdomide/Daratumumab/Dexamethasone Is Effective in ... The iberdomide-daratumumab-dexamethasone regimen achieved a 93.1% overall response rate in frail, transplant-ineligible multiple myeloma ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40346992/

EXCALIBER-RRMM: a phase III trial of iberdomide, ... EXCALIBER-RRMM is a unique confirmatory phase III trial that incorporates a 2-stage seamless design to firstly address dose optimization of IberDd.

5. hematologyadvisor.com hematologyadvisor.com/news/iberdomide-shows-promising-phase-3-results-in-r-r-multiple-myeloma/

Iberdomide Shows Promising Phase 3 Results in R/R ... Topline data were announced from a phase 3 trial evaluating iberdomide in combination with standard therapies in patients with RRMM.

6. bmsclinicaltrials.com bmsclinicaltrials.com/us/en/clinical-trials/NCT04975997

Trial ID CC-220-MM-002 | NCT04975997 - BMS Clinical Trials This is a multicenter, two-stage, randomized, controlled, open-label, Phase 3 study comparing the efficacy and safety of iberdomide in combination with ...