Iberdomide + Belantamab Mafodotin + Dexamethasone for Multiple Myeloma

Not currently recruiting at 37 trial locations

Overseen By Destin Carlisle

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Alliance for Clinical Trials in Oncology

Must not be taking: Strong CYP3A4 inhibitors, Strong CYP3A4 inducers

Disqualifiers: Uncontrolled HIV, Hepatitis B, Cardiac risk, others

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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for patients with multiple myeloma, a cancer affecting blood cells in the bone marrow. The study aims to determine the safest and most effective dose of three drugs: iberdomide, belantamab mafodotin, and dexamethasone. Iberdomide boosts the immune system, belantamab mafodotin (an antibody-drug conjugate) targets and kills cancer cells, and dexamethasone reduces inflammation and side effects. This trial is for patients whose multiple myeloma has returned or stopped responding to standard treatments and who have previously tried at least two other therapies without success. As a Phase 1 trial, the 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.

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 take strong CYP3A4 inhibitors or inducers, and you must stop these 14 days before starting the trial. It's best to discuss your current medications with the trial team.

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

Research shows that belantamab mafodotin, when used alone, can cause some side effects. The most serious include low platelet levels (cells that help blood clot) in about 23% of patients and low red blood cell levels (which carry oxygen) in 16% of patients. For those taking a combination that includes iberdomide, most experienced some side effects, with eye problems reported in 89% of cases.

Combining iberdomide with dexamethasone has shown a response rate of 30% to 50% in treating multiple myeloma, a type of blood cancer. While these treatments can be effective, understanding the possible side effects is important for those considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of iberdomide and belantamab mafodotin for treating multiple myeloma because it offers a new way to target the disease. Unlike standard treatments that usually focus on different mechanisms, belantamab mafodotin is an antibody-drug conjugate that delivers a potent anti-cancer agent directly to multiple myeloma cells, potentially reducing damage to healthy cells. Iberdomide, on the other hand, is an innovative cereblon E3 ligase modulator (CELMoD) that enhances immune response against cancer cells. This combination aims to improve effectiveness and minimize side effects, offering new hope for patients with this challenging condition.

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

In this trial, participants will receive different combinations of treatments. Research has shown that combining iberdomide with dexamethasone, as in one of the trial arms, helped 30% to 50% of patients with relapsed or refractory multiple myeloma, causing the cancer to shrink or stop growing in many cases. Belantamab mafodotin, another treatment option in this trial, demonstrated good results when used alone, especially after other treatments failed. When used together, iberdomide and belantamab mafodotin, as in another arm of this trial, may help slow or stop cancer growth. These treatments target proteins on cancer cells, leading to cell death. This offers hope for patients whose myeloma has returned or not responded to other treatments. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with multiple myeloma that has returned or isn't responding to treatment. Participants must have had at least two prior treatments and been exposed to specific drug classes, but not previously treated with iberdomide, belamaf, BCMA-directed therapy, or any monoclonal antibody within the last 2 weeks.

Inclusion Criteria

I have never had BCMA-targeted treatment.

I haven't had monoclonal antibody treatment in the last 2 weeks.

My blood tests show a 25% change in certain proteins or I have new cancer growths or high calcium.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Phase I Treatment

Patients receive iberdomide orally on days 1-21 and 29-49, belantamab mafodotin IV on day 1, and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days.

56 days per cycle

Multiple visits for drug administration and monitoring

Phase II Treatment

Patients are randomized to receive either belantamab mafodotin and dexamethasone or iberdomide, belantamab mafodotin, and dexamethasone. Cycles repeat every 56 days.

56 days per cycle

Multiple visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

Every 6 months for 3 years

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Belantamab Mafodotin
• Dexamethasone
• Iberdomide

Trial Overview The trial is testing a combination of an experimental drug called Iberdomide with two approved drugs: Belantamab Mafodotin and Dexamethasone. It aims to find out the safest dose and how effective this combo is in slowing down or stopping cancer growth in patients with relapsed/refractory multiple myeloma.

How Is the Trial Designed?

Group I: Phase II, Arm II (iberdomide, belantamab mafodotin) Experimental Treatment 10 Interventions

Patients receive iberdomide orally on days 1-21 and 29-49, belantamab mafodotin IV on day 1, and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo bone marrow biopsy and aspiration and blood sample collection throughout trial.

Group II: Phase I (iberdomide, belantamab mafodotin, dexamethasone) Experimental Treatment 10 Interventions

Patients receive iberdomide orally on days 1-21 and 29-49, belantamab mafodotin IV on day 1, and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo a bone marrow biopsy and aspiration and blood sample collection throughout trial.

Group III: Phase II, Arm I (belantamab mafodotin, dexamethasone) Active Control 9 Interventions

Patients receive belantamab mafodotin IV on day 1 and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients who progress may cross over to Arm II. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo a bone marrow biopsy and aspiration and blood sample collection throughout trial.

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Belantamab mafodotin (BLENREP) received accelerated FDA approval for treating relapsed or refractory multiple myeloma in adults who have undergone at least four prior therapies, showing an overall response rate of 31% to 34% in the DREAMM-2 trial with 2.5 or 3.4 mg/kg doses.

The most common side effect was keratopathy, affecting 71% to 77% of patients, leading to a boxed warning for ocular toxicity, indicating the need for careful monitoring and a restricted distribution program.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Belantamab Mafodotin for Patients with Relapsed or Refractory Multiple Myeloma. Baines, AC., Ershler, R., Kanapuru, B., et al.[2023]

In a real-world study of 106 patients with relapsed or refractory multiple myeloma, belantamab mafodotin (BM) demonstrated an overall response rate of 38.1% and a median overall survival of 9.3 months, indicating its efficacy as a treatment option for heavily pre-treated patients.

The treatment was associated with significant safety concerns, particularly ophthalmic adverse events, with 48% of patients experiencing eye-related issues, including keratopathy in 37.5% of cases, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world study of the efficacy and safety of belantamab mafodotin (GSK2857916) in relapsed or refractory multiple myeloma based on data from the nominative ATU in France: the IFM 2020-04 study. Talbot, A., Bobin, A., Tabone, L., et al.[2023]

In two cases of multiple myeloma resistant to conventional therapies, patients showed significant improvement after treatment with bortezomib and dexamethasone, with one patient experiencing a decrease in serum IgG from 8040 to 1020 mg/dl and another from 2140 to 623 mg/dl.

The combination therapy not only proved effective in reducing tumor markers but also resulted in milder adverse reactions when dexamethasone was added, suggesting it may help mitigate side effects associated with bortezomib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effective combination therapy of bortezomib and dexamethasone for two patients with refractory multiple myeloma]. Ikeda, H., Hayashi, T., Nojima, M., et al.[2015]

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 study of 156 patients with relapsed and refractory multiple myeloma, belantamab-mafodotin (belamaf) demonstrated an overall response rate of 41.8%, with significant improvements in progression-free survival for those achieving at least minimal response (MR).

The safety profile of belamaf was manageable, with corneal events being the most common adverse effects, affecting 87.9% of patients, though only 1.3% discontinued treatment due to ocular toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belantamab Mafodotin in Patients with Relapsed/Refractory Multiple Myeloma: Results of the Compassionate Use or the Expanded Access Program in Spain. de la Rubia, J., Alonso, R., Clavero, ME., et al.[2023]

In a real-world study of 28 multiple myeloma patients who had undergone a median of six prior treatments, belantamab-mafodotin demonstrated an overall response rate of 40%, with some patients achieving complete remission and a median overall survival of 8 months.

The treatment was generally well-tolerated, with keratopathy being the most common side effect in 32% of patients, but only leading to discontinuation in 11%, indicating a favorable safety profile in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of belantamab-mafodotin in triple-refractory multiple myeloma patients: A multicentric real-life experience. Iula, R., De Novellis, D., Trastulli, F., et al.[2022]

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 patients with newly diagnosed multiple myeloma, the modified regimen of bortezomib, thalidomide, and dexamethasone (VTd-mod) using a lower thalidomide dose (100 mg/day) was found to be noninferior to the traditional higher dose (VTd-label) in terms of overall survival and progression-free survival, while showing better post-transplant response rates.

The combination of daratumumab with the VTd regimen (D-VTd) demonstrated superior efficacy compared to the traditional VTd-label, while maintaining similar safety profiles, supporting its use as a first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety of bortezomib, thalidomide, and dexamethasone (VTd) without and with daratumumab (D-VTd) in CASSIOPEIA versus VTd in PETHEMA/GEM in transplant-eligible patients with newly diagnosed multiple myeloma, using propensity score matching. Moreau, P., Hulin, C., Zweegman, S., et al.[2023]

In a study of 44 patients with relapsed or refractory multiple myeloma, the combination of bortezomib and dexamethasone (BD) showed a significantly higher 1-year progression-free survival (PFS) rate of 45.5% compared to 31.8% for thalidomide and dexamethasone (TD).

Patients receiving BD also had a better overall survival rate at 3 years (70.0%) compared to those on TD (48.8%), although BD was associated with higher rates of certain adverse events like thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bortezomib plus dexamethasone vs thalidomide plus dexamethasone for relapsed or refractory multiple myeloma. Iida, S., Wakabayashi, M., Tsukasaki, K., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06232044

Study Details | NCT06232044 | Testing the Combination of ... Iberdomide plus belantamab mafodotin may help slow or stop the growth of cancer in patients with multiple myeloma.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11893888/

A real-world experience of efficacy and safety ... The best overall response (ORR) and complete response rates were 40.0 and 15.0%, respectively. ORRs were lower in patients with EMD, BCMA- ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.17_suppl.LBA105

Results from the randomized phase 3 DREAMM-8 study of ... In DREAMM-7, BVd led to a significant improvement in progression-free survival (PFS) and a strong trend in improved overall survival (OS) vs ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265025042302

Treatment of Myeloma Early Relapse –Non CAR-T Cell The DREAMM-7 trial evaluated the efficacy of BelaVd compared with DaraVd and demonstrated an improved median progression-free survival of 36.6 ...

5. onclive.com onclive.com/view/iberdd-demonstrates-positive-topline-efficacy-in-relapsed-refractory-multiple-myeloma

IberDd Demonstrates Positive Topline Efficacy in Relapsed ... Iberdomide combined with daratumumab and dexamethasone significantly improved MRD negativity rates in relapsed/refractory multiple myeloma ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37793771/

Efficacy and safety of single-agent belantamab mafodotin ... Most common grade 3-4 adverse events were thrombocytopenia (49 [23%] of 217) and anaemia (35 [16%]) for belantamab mafodotin, and neutropenia (34 [33%] of 102) ...

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

Iberdomide For example, combination therapy with iberdomide and dexamethasone (also called “IBER-dex”) has shown an overall response rate (ORR) of about 30% to 50% in ...