Belantamab Mafodotin for Multiple Myeloma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Systemic corticosteroids

Disqualifiers: Active infection, Cardiovascular risk, Hepatitis, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 14

Duration: Variable (3 to 6 weeks per cycle)

62 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests different doses and schedules of belantamab mafodotin for multiple myeloma, a type of blood cancer. This targeted therapy aims to attack specific markers on cancer cells and deliver chemotherapy directly to them. Researchers aim to determine if these variations can reduce side effects, such as eye issues, while effectively treating the cancer. This trial may suit those whose multiple myeloma has returned or does not respond to other treatments and who have already tried several different therapies. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that certain medications, like systemic corticosteroids, are allowed in emergency situations. It's best to discuss your specific medications with the trial team.

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

Research has shown that belantamab mafodotin, a treatment for multiple myeloma, is generally well-tolerated. In studies, some patients experienced side effects, with eye-related issues being the most common. These issues are usually mild, such as blurred vision or dry eyes. About 36.5% of patients delayed their treatment due to these side effects. Importantly, no new safety concerns have emerged compared to standard treatments. This suggests that belantamab mafodotin maintains a consistent safety profile for treating multiple myeloma, although monitoring for eye effects remains necessary. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple myeloma?

Researchers are excited about belantamab mafodotin for treating multiple myeloma because it works differently from standard treatments like proteasome inhibitors, immunomodulatory drugs, or monoclonal antibodies. Belantamab mafodotin is an antibody-drug conjugate that targets the BCMA protein on myeloma cells, delivering a toxic payload directly to the cancer cells, which helps minimize damage to healthy cells. This targeted approach not only has the potential to improve effectiveness but also reduces the side effects typically seen with broader treatments. This innovative mechanism of action offers hope for improved outcomes in patients with this challenging condition.

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

Research has shown that belantamab mafodotin can help treat multiple myeloma, particularly in patients who have not responded to other treatments. One study found that about 36% of patients responded well, with their cancer shrinking or disappearing. Another study found that, when combined with other drugs, it reduced the risk of death by 42%. Patients experienced an average of 2.8 months during which their cancer did not worsen. In this trial, participants will receive either a low dose or a combination of low and high doses of belantamab mafodotin. These findings suggest that belantamab mafodotin offers hope for patients with hard-to-treat multiple myeloma. ^{3 6 7 8 9}

Who Is on the Research Team?

Ricardo D. Parrondo, M.D.

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

Adults with multiple myeloma that's resistant to standard treatments, including proteasome inhibitors, immunomodulatory agents, and anti-CD38 monoclonal antibodies. Participants must have adequate organ function and not be pregnant or planning to become pregnant. They should not have certain other medical conditions like active infections or recent major surgery.

Inclusion Criteria

My diagnosis of multiple myeloma is confirmed by lab tests.

Your absolute neutrophil count is equal to or higher than 1.0 x 10^9 per liter.

Provide written informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the study protocol

Exclusion Criteria

I am currently being treated for an infection.

I am HIV positive.

My liver condition is stable.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Patients receive belantamab mafodotin intravenously on day 1 of each cycle. Cycles repeat every 3 to 6 weeks depending on the group, in the absence of disease progression or unacceptable toxicity.

Variable (3 to 6 weeks per cycle)

1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 12 weeks for up to 5 years.

Up to 5 years

Every 12 weeks (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Belantamab Mafodotin

Trial Overview The trial is testing different doses and schedules of Belantamab Mafodotin for relapsed/refractory multiple myeloma. This drug targets cancer cells by attaching to BCMA receptors on their surface and delivering a chemotherapy agent directly to them.

How Is the Trial Designed?

Group I: Group II (low dose and high dose belantamab mafodotin) Experimental Treatment 7 Interventions

Patients receive belantamab mafodotin IV on day 1. Cycle repeats at 3 weeks for the next cycle and then every 6 weeks for subsequent cycles in the absence of disease progression or unacceptable toxicity. All patients undergo a CT scan, a MRI scan, or a PET/CT scan during screening and patients with plasmacytoma (a MM tumor in bone or soft tissue) also undergo imaging scans on study. Patients undergo bone marrow aspirate and biopsy during screening and on study as well as collection of blood samples throughout the trial.

Group II: Group I (low dose belantamab mafodotin) Active Control 7 Interventions

Patients receive low dose belantamab mafodotin intravenously (IV) on day 1 of each cycle. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. All patients undergo a CT scan, a MRI scan, or a PET/CT scan during screening and patients with plasmacytoma (a MM tumor in bone or soft tissue) also undergo imaging scans on study. Patients undergo bone marrow aspirate and biopsy during screening and on study as well as collection of blood samples throughout the trial.

Belantamab Mafodotin is already approved in European Union, United States for the following indications:

Approved in European Union as Blenrep for:

• Relapsed or refractory multiple myeloma

Approved in United States as Blenrep for:

• Relapsed or refractory multiple myeloma

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

Belantamab mafodotin, an antibody-drug conjugate, has shown significant efficacy and manageable safety in treating heavily pretreated relapsed/refractory multiple myeloma, as demonstrated in the phase I DREAMM-1 and phase II DREAMM-2 studies.

The recommended dose of belantamab mafodotin is 2.5 mg/kg every 3 weeks, with safety outcomes like corneal events and thrombocytopenia being closely linked to drug exposure, highlighting the importance of monitoring patient characteristics and disease burden in treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure-Response Analyses for Therapeutic Dose Selection of Belantamab Mafodotin in Patients With Relapsed/Refractory Multiple Myeloma. Ferron-Brady, G., Rathi, C., Collins, J., et al.[2022]

Belantamab mafodotin (belamaf) significantly improves overall survival (OS) and duration of response (DoR) in patients with relapsed/refractory multiple myeloma compared to selinexor plus low-dose dexamethasone, with a hazard ratio of 0.53 for OS and 0.41 for DoR, indicating its efficacy as a treatment option.

Belamaf also shows a favorable safety profile, with fewer severe adverse events compared to selinexor plus dexamethasone, making it a promising single-agent therapy for patients who have already undergone multiple lines of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DREAMM-2: Indirect Comparisons of Belantamab Mafodotin vs. Selinexor + Dexamethasone and Standard of Care Treatments in Relapsed/Refractory Multiple Myeloma. Prawitz, T., Popat, R., Suvannasankha, A., et al.[2022]

Belantamab mafodotin is a first-in-class monoclonal antibody-drug conjugate designed to treat relapsed or refractory multiple myeloma by targeting B-cell maturation antigen (BCMA) and delivering a cytotoxic agent directly to cancer cells.

It received regulatory approval in the USA and EU in August 2020 based on promising results from the DREAMM-2 trial, specifically for patients who have undergone at least four prior therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belantamab Mafodotin: First Approval. Markham, A.[2021]

In the DREAMM-2 study, after 13 months of follow-up, 32% of patients with relapsed or refractory multiple myeloma achieved an overall response to belantamab mafodotin (belamaf) at a dose of 2.5 mg/kg, indicating its efficacy in a heavily pretreated population.

The study found that belamaf maintained clinical activity without new safety concerns, even in patients experiencing prolonged dose delays due to corneal events, suggesting it is a safe treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longer term outcomes with single-agent belantamab mafodotin in patients with relapsed or refractory multiple myeloma: 13-month follow-up from the pivotal DREAMM-2 study. Lonial, S., Lee, HC., Badros, A., et al.[2022]

In a study of 106 heavily pretreated patients with relapsed/refractory multiple myeloma, belantamab mafodotin showed an overall response rate of 45.5% and a median overall survival of 14.5 months, indicating its efficacy in a real-world setting.

The treatment was associated with significant adverse effects, particularly ocular toxicity (68.4% experienced keratopathy), but the overall toxicity profile was considered tolerable, suggesting that the benefits may outweigh the risks for many patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience with belantamab mafodotin therapy for relapsed/refractory multiple myeloma: A multicentre retrospective study. Shragai, T., Magen, H., Lavi, N., 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]

Belantamab mafodotin (belamaf) is an approved treatment for adults with relapsed/refractory multiple myeloma, showing effectiveness by targeting BCMA and eliminating myeloma cells through multiple mechanisms.

The ongoing DREAMM-5 study is exploring the safety and efficacy of belamaf in combination with other novel therapies, which may enhance its anticancer effects compared to belamaf alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belantamab mafodotin in combination with novel agents in relapsed/refractory multiple myeloma: DREAMM-5 study design. Nooka, AK., Weisel, K., van de Donk, NW., et al.[2021]

Belantamab mafodotin (belamaf) is an effective treatment for relapsed or refractory multiple myeloma, showing a 32% overall response rate in the phase II DREAMM-2 study with 95 patients.

While most patients experienced microcyst-like epithelial changes (MECs) as a side effect, these were generally manageable, with a high resolution rate and no permanent vision loss reported, indicating a need for careful monitoring and collaboration between eye care and oncology professionals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corneal Epithelial Findings in Patients with Multiple Myeloma Treated with Antibody-Drug Conjugate Belantamab Mafodotin in the Pivotal, Randomized, DREAMM-2 Study. Farooq, AV., Degli Esposti, S., Popat, R., et al.[2020]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10543185/

Real-world study of the efficacy and safety of belantamab ... At 12±3 weeks, ORR was 35.6 % (26/73), including five patients (6.8%) with a complete response (CR), seven (9.6%) with a very good partial response (VGPR), and ...

2. nature.com nature.com/articles/s41408-025-01226-8

A real-world experience of efficacy and safety ... In summary, belantamab mafodotin appeared safe and relatively effective in this real-world heavily pretreated RRMM population, where the ...

3. gsk.com gsk.com/en-gb/media/press-releases/blenrep-shows-significant-overall-survival-benefit-reducing-the-risk-of-death-by-42-in-multiple-myeloma-at-or-after-first-relapse/

Blenrep shows significant overall survival benefit, reducing ... The analysis presented today shows a statistically significant 42% reduction in the risk of death among patients receiving the belantamab mafodotin combination.

4. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/4751/533572/Final-Results-of-Phase-1-Clinical-Trial-of

Final Results of Phase 1 Clinical Trial of Belantamab ... In the DREAMM-7 study, Belamaf showed superior efficacy outcomes compared to daratumumab when combined with bortezomib and dexamethasone.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265025001387

Treatment Patterns, Efficacy, and Tolerability of ... At 13-month follow-up, overall response rate (ORR) was 32%, median progression-free survival (PFS) 2.8 months, median duration of response (DOR) 11.0 months, ...

6. gsk.com gsk.com/en-gb/media/press-releases/blenrep-approved-by-us-fda-for-use-in-treatment-of-relapsedrefractory-multiple-myeloma/

Blenrep approved by US FDA for use in treatment of ... Interim efficacy and safety data for Blenrep as a first line treatment are expected in early 2028 with enrolment expanded to US sites to ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37078253/

Real-world study of the efficacy and safety of belantamab ... Treatment was delayed for 55 (52.9%) patients including 36.5% for treatment-related toxicity. Ophthalmic adverse events, mainly grade ≤2, were ...

8. haematologica.org haematologica.org/article/view/haematol.2022.281772

Real-world study of the efficacy and safety of belantamab ... “Real-life” data of the efficacy and safety of belantamab mafodotin in relapsed multiple myeloma- the Mayo Clinic experience. Blood. 2021 ...

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

Efficacy and safety of single-agent belantamab mafodotin ... Belantamab mafodotin was not associated with statistically improved progression-free survival compared with standard-of-care, but there were no new safety ...