Iberdomide + Belantamab Mafodotin + Dexamethasone for Multiple Myeloma

Recruiting at 34 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

88 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I/II trial tests the safety, side effects, best dose, and effectiveness of iberdomide in combination with belantamab mafodotin and dexamethasone in treating patients with multiple myeloma (MM) that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). Multiple myeloma is a cancer that affects white blood cells called plasma cells, which are made in the bone marrow and are part of the immune system. Multiple myeloma cells have a protein on their surface called B-cell maturation antigen (BCMA) that allows the cancer cells to survive and grow. Immunotherapy with iberdomide, may induce changes in body's immune system and may interfere with the ability of cancer cells to grow and spread. Belantamab mafodotin has been designed to attach to the BCMA protein, which may cause the myeloma cell to become damaged and die. Dexamethasone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Iberdomide plus belantamab mafodotin may help slow or stop the growth of cancer in patients with multiple myeloma.

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.

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

Research shows that combining dexamethasone with other drugs like bortezomib or iberdomide can be effective in treating multiple myeloma, especially in patients who have not responded to other treatments. Iberdomide has shown promise in enhancing the effects of other drugs in preclinical models, suggesting potential benefits when used with dexamethasone. ^{1 2 3 4 5}

What safety information is available for the treatment with Belantamab Mafodotin in multiple myeloma patients?

Belantamab Mafodotin has been studied in multiple myeloma patients and common side effects include eye problems like keratopathy (eye damage) and changes in vision, which can be serious. Other side effects include low blood platelet levels and infections, but these are generally manageable with proper monitoring and care. ^{6 7 8 9 10}

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

This drug combination is unique because Iberdomide is a novel agent that enhances the immune system and works well with other drugs like dexamethasone, while Belantamab Mafodotin is an antibody-drug conjugate that targets and kills cancer cells directly. This combination offers a new approach for patients who have already tried other treatments. ^{1 2 4 5 11}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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]

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 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]

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]

References

1. China pubmed.ncbi.nlm.nih.gov

Bortezomib, dexamethasone plus thalidomide for treatment of newly diagnosed multiple myeloma patients with or without renal impairment. [2021]

2. Japan pubmed.ncbi.nlm.nih.gov

[Effective combination therapy of bortezomib and dexamethasone for two patients with refractory multiple myeloma]. [2015]

3. England pubmed.ncbi.nlm.nih.gov

Bortezomib plus dexamethasone vs thalidomide plus dexamethasone for relapsed or refractory multiple myeloma. [2021]

4. 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]

5. United States 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. [2023]

6. Switzerland 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. [2023]

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

FDA Approval Summary: Belantamab Mafodotin for Patients with Relapsed or Refractory Multiple Myeloma. [2023]

8. Italy 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. [2023]

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

EMA Review of Belantamab Mafodotin (Blenrep) for the Treatment of Adult Patients with Relapsed/Refractory Multiple Myeloma. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of belantamab-mafodotin in triple-refractory multiple myeloma patients: A multicentric real-life experience. [2022]

11. 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]