Belantamab Mafodotin for Multiple Myeloma

(DREAMM-3 Trial)

Recruiting at 146 trial locations

Overseen By EU GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: GlaxoSmithKline

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

325 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called belantamab mafodotin in patients with multiple myeloma that has returned or not responded to treatment. Belantamab mafodotin targets cancer cells directly, while pomalidomide boosts the immune system, and dexamethasone controls inflammation.

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.

What data supports the effectiveness of the drug Belantamab Mafodotin for treating multiple myeloma?

Belantamab Mafodotin has shown effectiveness in treating relapsed or refractory multiple myeloma, with a response rate of about 31-34% in patients who have tried several other treatments. However, it can cause eye-related side effects, and its approval is based on early trial results, with further studies needed to confirm its benefits. ^{1 2 3 4 5}

What safety data exists for Belantamab Mafodotin in humans?

Belantamab Mafodotin has been associated with eye-related side effects, such as changes in vision and dry eyes, in a significant number of patients. It carries a warning for eye toxicity and is available only through a special program to manage these risks. ^{1 3 5 6 7}

What makes the drug Belantamab Mafodotin unique for treating multiple myeloma?

Belantamab Mafodotin is unique because it is a first-in-class antibody-drug conjugate (a type of targeted cancer therapy) that delivers a toxic substance directly to myeloma cells, offering a new option for patients who have already tried multiple other treatments. It is administered intravenously and has shown effectiveness in patients with relapsed or refractory multiple myeloma, but it requires careful monitoring due to potential eye-related side effects. ^{1 3 5 7 8}

Research Team

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Eligibility Criteria

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.

I am at least 18 years old, or over 19 if I am from the Republic of Korea.

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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) 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 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) 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]

References

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

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

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

Single-agent belantamab mafodotin in patients with relapsed/refractory multiple myeloma: Final analysis of the DREAMM-2 trial. [2023]

3. United States 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. [2022]

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

Explosive Disease Progression After Single-Agent B-cell Maturation Antigen-Targeted Treatment in Multiple Myeloma: A Report of Three Cases in Sheikh Shakhbout Medical City. [2023]

5. England 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. [2020]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Belantamab Mafodotin: First Approval. [2021]

7. United States 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. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Belantamab mafodotin in combination with novel agents in relapsed/refractory multiple myeloma: DREAMM-5 study design. [2021]