Belantamab Mafodotin for Lymphoma

No longer recruiting at 3 trial locations

Overseen By Andrew Zelenetz, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Jacob Soumerai, MD

Must not be taking: Investigational agents

Disqualifiers: Corneal disease, CNS involvement, 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: 27

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called belantamab mafodotin for individuals with certain types of lymphoma (a cancer of the lymphatic system) that haven't responded to other treatments. The study aims to determine if this drug is safe and effective in targeting and killing cancer cells. It is designed for those with plasmablastic lymphoma or ALK+ large B-cell lymphoma who have already tried other treatments without success. Participants should have a measurable form of the disease and must have previously attempted systemic therapies. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering a chance to benefit from a potentially effective new therapy.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have used an investigational drug or approved systemic lymphoma therapy within 14 days before the first dose of the study drug, except for steroids, which are allowed.

Is there any evidence suggesting that belantamab mafodotin is likely to be safe for humans?

Research has shown that belantamab mafodotin was safe in earlier studies. In trials involving patients with multiple myeloma, this treatment was generally well-tolerated, with most side effects being mild and manageable.

Past studies reported common side effects such as vision changes and low blood cell counts. However, these effects were usually temporary and improved with proper care. Notably, belantamab mafodotin is already approved for other conditions, which adds confidence to its safety.

Overall, the treatment has proven effective while maintaining a good safety record in patients with similar conditions. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Belantamab mafodotin is unique because it combines a monoclonal antibody with a cytotoxic agent, specifically targeting cancer cells in lymphoma. Unlike traditional chemotherapy, which affects both healthy and cancerous cells, belantamab mafodotin aims directly at the cancer cells, potentially reducing side effects. Researchers are excited because this targeted approach could improve treatment effectiveness and patient quality of life by minimizing the collateral damage seen with existing treatments like R-CHOP and other standard regimens.

What evidence suggests that belantamab mafodotin might be an effective treatment for lymphoma?

Studies have shown that belantamab mafodotin can help treat certain blood cancers. It combines a protein and a drug to target and kill cancer cells. Earlier research demonstrated its benefits for patients with relapsed or hard-to-treat multiple myeloma, a type of blood cancer. Patients who received this treatment experienced positive results, although some encountered manageable side effects, such as eye problems. This trial will investigate belantamab mafodotin for its potential in treating other similar conditions, like plasmablastic lymphoma or ALK+ large B-cell lymphoma. ^{2 6 7 8 9}

Who Is on the Research Team?

Jacob D. Soumerai, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

Adults with relapsed or refractory plasmablastic lymphoma or ALK+ large B-cell lymphoma who have measurable disease and have previously undergone systemic lymphoma therapy. Participants must be in relatively good health (ECOG ≤2), not pregnant, using contraception, able to consent, and without serious concurrent illnesses or recent treatments that could interfere.

Inclusion Criteria

I have a tumor that can be measured and is at least 10mm or 15mm big depending on its location.

I don't have any other cancer affecting my current treatment.

Your platelet count must be at least 50,000 per microliter.

Exclusion Criteria

I have a mild eye surface condition.

I have no major side effects from previous cancer treatments.

I do not have any uncontrolled illnesses or active infections.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive belantamab mafodotin intravenously on day 1 of a 21-day cycle until progression or intolerance

Up to 2 years

Every 21 days (outpatient)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Belantamab Mafodotin

Trial Overview The trial is testing the safety and effectiveness of belantamab mafodotin, an antibody-drug conjugate designed to target and kill lymphoma cells. It's for patients whose cancer has returned after treatment or didn't respond to previous therapies.

How Is the Trial Designed?

Group I: (BELANTAMAB MAFODOTIN Experimental Treatment 1 Intervention

* Belantamab mafodotin will be administered intravenously on day 1 of a 21-day cycle. * Treatment is intended to be administered on an outpatient basis.

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?

Jacob Soumerai, MD

Lead Sponsor

Trials

2

Recruited

30+

GlaxoSmithKline

Industry 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, 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 (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]

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 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]

The budget impact analysis of belantamab mafodotin (belamaf) for patients with relapsed/refractory multiple myeloma indicates that its introduction would be budget neutral for a US health plan, with minimal cost changes over 3 years.

In a hypothetical health plan with 1 million members, only 33 patients were identified as eligible for treatment, and the analysis showed that the budget impact was most sensitive to treatment duration and drug acquisition costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Budget Impact of Belantamab Mafodotin (Belamaf) Adoption in the Treatment of Patients with Relapsed or Refractory Multiple Myeloma in the United States. Shah, A., Tosh, JC., Ambavane, A., et al.[2022]

Citations

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

Treatment Patterns, Efficacy, and Tolerability of ... Conclusion: Despite a high incidence of manageable keratopathy, these data demonstrate benefit in belantamab mafodotin in patients with RRMM over an extended ...

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

Treatment Patterns, Efficacy, and Tolerability of ... The efficacy and safety profile of 2.5 mg/kg was favorable compared to 3.4 mg/kg.9 Subsequently, the DREAMM-3 trial compared belantamab mafodotin to ...

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

Real-world study of the efficacy and safety of belantamab ... Longer term outcomes with single-agent belantamab mafodotin in patients with relapsed or refractory multiple myeloma: 13-month follow-up ...

4. bloodcancerstoday.com bloodcancerstoday.com/post/fdas-odac-votes-belantamab-mafodotin-at-proposed-dosing-unfavorable-in-multiple-myeloma

FDA's ODAC Votes Belantamab Mafodotin at Proposed ... “The available data also suggest that lower exposure of belantamab mafodotin may result in fewer dose modifications and corneal adverse events ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05874193

A Collaborative Community Effort Using Belantamab ... This is a research study to find out if a drug called belantamab mafodotin in combination with dexamethasone, a steroid, can be safely and effectively given ...

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

Real-world study of the efficacy and safety of belantamab ... The primary outcome was to evaluate the efficacy and safety of BM (GSK2857916) ... Belantamab mafodotin proved effective in the phase II DREAMM-2 trial. Based ...

7. onclive.com onclive.com/view/fda-approves-belantamab-mafodotin-plus-bortezomib-and-dexamethasone-for-r-r-multiple-myeloma

FDA Approves Belantamab Mafodotin Plus Bortezomib and ... ... trial results. BVd showed a 51% reduction in death risk and improved progression-free survival compared to DVd in the trial. Safety concerns ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10251850/

Belantamab Mafodotin: From Clinical Trials Data to Real-Life ... Belantamab Mafodotin, a first-in-class anti-BCMA antibody–drug conjugate, demonstrated good efficacy and safety profile in triple-refractory patients in the ...

9. clinical-lymphoma-myeloma-leukemia.com clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(25)00138-7/abstract

A Real-World Analysis Real-world study of the efficacy and safety of belantamab mafodotin (GSK2857916) in relapsed or refractory multiple myeloma based on data from the ...