Belantamab Mafodotin for Multiple Myeloma

(DREAMM-3 Trial)

Not currently recruiting at 191 trial locations

Overseen By EU GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: GlaxoSmithKline

Must not be taking: Anti-MM antibodies, BCMA-targeted

Disqualifiers: Amyloidosis, Plasma cell leukemia, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 55 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, belantamab mafodotin (an antibody-drug conjugate), against the standard treatment of pomalidomide plus dexamethasone for individuals with multiple myeloma, a type of blood cancer. The researchers aim to determine which treatment is more effective and safer for patients whose cancer has returned or hasn't responded to at least two other treatments. Participants will receive one of the two treatments until their cancer worsens or they experience unacceptable side effects. Suitable candidates for this trial have had multiple myeloma, tried at least two other treatments, and have either undergone a stem cell transplant or are unable to have one. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to the development of a promising new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have had systemic anti-myeloma therapy or an investigational drug within 14 days before starting the study treatment.

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, has been tested for safety in humans. Studies have found that the most common side effects involve the eyes, such as mild vision changes or discomfort, occurring in about 48% of patients. Specifically, keratopathy, a condition affecting the eye's outer layer, appeared in 37.5% of cases.

The FDA has approved belantamab mafodotin for treating relapsed or refractory multiple myeloma, indicating trust in its safety when used correctly. While generally well-tolerated, participants should be aware of these possible side effects and discuss them with their healthcare providers. ^{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 multiple myeloma because it offers a novel approach by utilizing an antibody-drug conjugate. Unlike standard treatments such as lenalidomide or bortezomib, which target the cancer through different mechanisms, Belantamab Mafodotin specifically targets B-cell maturation antigen (BCMA) on myeloma cells, delivering a potent chemotherapy directly to them. This targeted delivery method is hoped to minimize damage to healthy cells and reduce side effects. Additionally, it is administered less frequently, which could improve patient comfort and compliance.

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

Research has shown that belantamab mafodotin, which participants in this trial may receive, may help treat relapsed or refractory multiple myeloma (RRMM), a type of blood cancer. In earlier studies, it lowered the risk of death by 51% and even tripled survival rates for some patients. Real-world studies have also confirmed its effectiveness and general safety for people with RRMM. This drug targets and kills cancer cells, offering a new option for those who haven't responded to other treatments. These findings suggest belantamab mafodotin could be an effective treatment for people dealing with this difficult condition. Meanwhile, another group of participants in this trial will receive pomalidomide plus low-dose dexamethasone, tested as an active comparator. ^{2 3 6 7 8}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Are You a Good Fit for This Trial?

Adults with relapsed/refractory multiple myeloma who've had at least two prior treatments, including lenalidomide and a proteasome inhibitor, can join. They must have measurable disease levels, adequate organ function, and no major surgery or active infections recently. Pregnant women, those with certain medical conditions or previous BCMA-targeted therapy are excluded.

Inclusion Criteria

Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies

My side effects from previous treatments are mild, except for hair loss and some nerve pain.

You have specific levels of proteins in your blood and urine that can be measured.

Exclusion Criteria

I have had pneumonitis treated with steroids or have it now.

I am currently experiencing bleeding from an internal site.

I have symptoms of amyloidosis, POEMS syndrome, or plasma cell leukemia currently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either belantamab mafodotin every 3 weeks or pomalidomide daily with dexamethasone weekly in 28-day cycles until disease progression or other criteria are met

Up to 55 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Belantamab Mafodotin
• Pomalidomide plus low dose Dexamethasone

Trial Overview The trial compares belantamab mafodotin (administered every three weeks) against pomalidomide plus low-dose dexamethasone (pomalidomide daily for 21 days of a 28-day cycle; dexamethasone weekly). Participants will be randomly assigned to one of these treatments until their disease progresses or they experience unacceptable side effects.

How Is the Trial Designed?

Group I: Participants receiving Belantamab mafodotin Experimental Treatment 1 Intervention

Participants will receive belantamab mafodotin single agent dose on Day 1 of Q3W

Group II: Participants receiving pom/dex Active Control 1 Intervention

Participants will receive pomalidomide daily on Days 1 to 21 of each 28-day cycle, with dexamethasone once weekly on Days 1, 8, 15 and 22.

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?

GlaxoSmithKline

Lead Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

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]

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]

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]

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 (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]

Citations

1. 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 ... Significant unmet need for patients requires new and novel treatments1; DREAMM-7 showed a 51% reduction in the risk of death and tripled ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40348718/

Treatment Patterns, Efficacy, and Tolerability of ... Treatment Patterns, Efficacy, and Tolerability of Belantamab Mafodotin in Patients With Relapsed and/or Refractory Multiple Myeloma: A Real-World Analysis.

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

A real-world experience of efficacy and safety ... We report the real-world safety and efficacy outcomes of standard-of-care belantamab mafodotin for RRMM, with the aim to determine the patterns of its use in a ...

4. 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 ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04246047

Study Details | NCT04246047 | Evaluation of Efficacy and ... This is a Phase 3, randomized, open-label study designed to evaluate safety and efficacy of belantamab mafodotin in combination with bortezomib/dexamethasone ( ...

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

Real-world study of the efficacy and safety of belantamab ... Ophthalmic adverse events, mainly grade ≤2, were the most common toxicity (48%). The occurrence of keratopathy was 37.5%. Overall, our data are ...

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

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;11(12):196. [DOI] ...

8. ashpublications.org ashpublications.org/bloodneoplasia/article/2/3/100103/536762/Belantamab-mafodotin-in-patients-with-relapsed

Belantamab mafodotin in patients with relapsed/refractory ... Key PointsBelantamab mafodotin showed ORR 45%, PFS 3.8 months, and OS 17.2 months in relapsed/refractory multiple myeloma in a real-world ...