Belantamab Mafodotin for Multiple Myeloma

(DREAMM12 Trial)

Recruiting at 28 trial locations

Overseen By EU GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: GlaxoSmithKline

Must not be taking: Strong OATP inhibitors

Disqualifiers: Active infection, Cardiovascular risk, Hepatitis, others

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

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

Compensation: Varies

Number of Visits: 3

Duration: Up to 48 months

36 Participants Needed

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 people with multiple myeloma, a type of blood cancer. It aims to assess the treatment's safety and effectiveness, particularly for those with kidney issues often linked to this condition. The study is divided into parts, testing different doses in individuals with normal to severely impaired kidney function, including those on dialysis. Ideal candidates for this trial have tried at least two different treatments for multiple myeloma and experience kidney issues that affect daily life. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this 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 cannot have received an investigational drug or a strong Organic-anion transporting polypeptide inhibitor within 14 days or 5 half-lives before the first dose of the study drug. It's best to discuss your current medications with the trial team.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants should not have received certain investigational drugs or strong inhibitors within a specific timeframe before the study. It's best to discuss your current medications with the study team to get a clear answer.

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

Research has shown that belantamab mafodotin has been tested for safety in people with multiple myeloma, a type of blood cancer. In studies involving 218 patients, some received the treatment for six months or more. The treatment is generally considered safe, but like many cancer drugs, it can cause side effects. The FDA has already approved it for patients whose cancer has returned after other treatments.

Real-world studies have found that many patients tolerated belantamab mafodotin well. However, some experienced side effects, which is common with cancer treatments. Anyone considering joining a trial should discuss possible side effects and safety concerns with their doctor. ^{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 works differently from standard treatments like proteasome inhibitors and immunomodulatory drugs. Belantamab mafodotin is an antibody-drug conjugate targeting the BCMA (B-cell maturation antigen) on myeloma cells, delivering a potent toxin directly to cancer cells. This targeted approach could lead to better outcomes by minimizing damage to healthy cells. Additionally, its novel mechanism of action offers hope for patients who may not respond to existing therapies, potentially leading to more effective and personalized treatment options.

What evidence suggests that belantamab mafodotin could be an effective treatment for multiple myeloma?

Research shows that belantamab mafodotin may help treat relapsed and refractory multiple myeloma (RRMM). Studies have found that about 7 out of 10 patients experienced noticeable improvement. In one study, patients lived for an average of 8.1 months without their cancer worsening, and many saw a significant reduction in their tumors. In this trial, participants will receive belantamab mafodotin in different treatment arms based on their renal function to evaluate its safety and effectiveness. Overall, belantamab mafodotin appears to be a safe and effective option for those who have tried several other treatments. ^{2 6 7 8 9}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Are You a Good Fit for This Trial?

This trial is for adults with multiple myeloma who've had at least 3 prior treatments (or 2 if they couldn't have a stem cell transplant) and have varying degrees of kidney function, including severe impairment or end-stage renal disease. Participants must be able to consent, follow study rules, and use contraception.

Inclusion Criteria

I am using birth control as required by local laws for clinical study participants.

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

Main additional inclusion criteria in Group 1 (matched control participants)

Exclusion Criteria

I haven't taken any experimental drugs within the last 14 days or 5 half-lives, whichever is shorter.

I have had a stem cell transplant from a donor.

I have not undergone plasmapheresis within the last week.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive belantamab mafodotin monotherapy with dosing every 21 days until disease progression or other endpoints

Up to 48 months

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Post Analysis Continued Treatment (PACT)

Participants may continue treatment based on analysis of safety and pharmacokinetic data

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Belantamab mafodotin

Trial Overview The trial tests belantamab mafodotin monotherapy in multiple myeloma patients with different levels of kidney health. It's given intravenously every three weeks. The study has two parts based on the severity of renal dysfunction and includes screening, treatment, follow-up, and continued treatment phases.

How Is the Trial Designed?

Group I: Part 2: Participants with ESRD (on hemodialysis) Experimental Treatment 1 Intervention

Participants with ESRD (iGFR: \<15 mL/min) on hemodialysis will be administered with belantamab mafodotin either 2.5 mg/kg or 1.9 mg/kg (or other adjusted dose) as an intravenous infusion over 30 minutes Q3W on Day 1 of every 21-day cycle until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, or end of study, whichever occurs first. In Part 2, the dose will be decided after evaluation of pharmacokinetic and safety data of Part 1.

Group II: Part 2: Participants with ESRD (not on dialysis) Experimental Treatment 1 Intervention

Participants with ESRD (iGFR: \<15 mL/min) not on dialysis will be administered with belantamab mafodotin either 2.5 mg/kg or 1.9 mg/kg (or other adjusted dose) as an intravenous infusion over 30 minutes Q3W on Day 1 of every 21- day cycle until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, or end of study, whichever occurs first. In Part 2, the dose will be decided after evaluation of pharmacokinetic and safety data of Part 1.

Group III: Part 1: Participants with severe renal impairment Experimental Treatment 1 Intervention

Participants with severely impaired renal function (iGFR: 15-29 mL/min) will be administered with belantamab mafodotin 2.5 mg/kg as an intravenous infusion over 30 minutes Q3W on Day 1 of every 21- day cycle until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, or end of study, whichever occurs first.

Group IV: Part 1: Participants with normal/mild impaired renal function Experimental Treatment 1 Intervention

Participants with normal or mildly impaired renal function (Normal: individual glomerular filtration rate \[iGFR\]: \>=90 milliliter per minute; Mild impairment: iGFR: 60-89 mL/min will be administered with belantamab mafodotin 2.5 mg/kg as an intravenous infusion over 30 minutes Q3W on Day 1 of every 21- day cycle until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, or end of study, whichever occurs first.

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

Approved in United States as Blenrep for:

• Relapsed or refractory multiple myeloma (approval withdrawn)

Approved in European Union 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 (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, 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 (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 the DREAMM-2 study involving 196 patients with relapsed or refractory multiple myeloma, belantamab mafodotin demonstrated anti-myeloma activity, with overall response rates of 31% in the 2.5 mg/kg cohort and 34% in the 3.4 mg/kg cohort.

The treatment had a manageable safety profile, with common grade 3-4 adverse events including keratopathy and thrombocytopenia, and only two treatment-related deaths, indicating that while there are risks, the benefits may outweigh them for patients with limited options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study. Lonial, S., Lee, HC., Badros, A., et al.[2020]

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 (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. 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 ...

2. ashpublications.org ashpublications.org/bloodadvances/article/9/9/2155/535577/Prior-exposure-to-belantamab-mafodotin-influences

Prior exposure to belantamab mafodotin influences outcomes ... The median progression-free survival (PFS) with belantamab was 8.1 months, and the median time from the last dose of belantamab to ide-cel was ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e19512

Targeting BCMA in relapsed and refractory multiple myeloma Efficacy analysis revealed that the pooled ORR was 68.4% (95% CI: 61.2–75.6), with ≥very good partial response achieved in 65.2% (95% CI: 57.4– ...

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

Treatment Patterns, Efficacy, and Tolerability of ... This single-site, retrospective study examined 30 adults with multiple myeloma receiving care at Duke Cancer Institute who began belantamab mafodotin ...

5. 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.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2020/761158s000lbl.pdf

Blenrep (belantamab mafodotin-blmf) - accessdata.fda.gov Among the 218 patients, 24% were exposed for 6 months or longer. Relapsed or Refractory Multiple Myeloma. The safety of BLENREP as a single agent was evaluated ...

7. 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 ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10380484/

Real-World Effectiveness and Safety of Belantamab ... Belantamab mafodotin has been approved for patients with triple-class refractory relapsed/refractory multiple myeloma (RRMM) who have received ...

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

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