Belantamab Mafodotin + Lenalidomide for Multiple Myeloma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Roswell Park Cancer Institute

Must not be taking: Antibiotics, Antivirals, Antifungals, others

Disqualifiers: Active infection, Uncontrolled hypertension, 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

Compensation: Varies

Number of Visits: 11

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how two treatments, belantamab mafodotin and lenalidomide, can benefit people with multiple myeloma, a type of blood cancer. The researchers aim to determine if these treatments can prevent cancer from returning after a stem cell transplant. Belantamab mafodotin targets cancer cells directly, while lenalidomide inhibits cancer growth. The trial seeks participants who have undergone a stem cell transplant but still show signs of the disease. 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. It's best to discuss this with the trial team or your doctor.

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

Research has shown that combining belantamab mafodotin and lenalidomide is generally safe for many patients. In studies, the combination of belantamab mafodotin with lenalidomide and dexamethasone was mostly well-tolerated, with no new safety issues identified. However, some common side effects included keratopathy, which affects the eyes.

Lenalidomide is a well-known treatment for multiple myeloma and is usually safe when used as directed. While side effects can occur, these treatments aim to balance effectiveness with manageable side effects. Prospective trial participants should consult their healthcare provider to understand how these findings might relate to their health needs. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Belantamab Mafodotin and Lenalidomide for treating multiple myeloma because this approach introduces a unique mechanism of action. Unlike standard treatments like proteasome inhibitors and immunomodulatory drugs, Belantamab Mafodotin is an antibody-drug conjugate targeting the B-cell maturation antigen (BCMA) on myeloma cells, delivering a potent cytotoxic agent directly to the cancer cells. This targeted delivery is expected to enhance the effectiveness while potentially reducing side effects compared to traditional therapies. Additionally, combining it with Lenalidomide, an existing treatment that modulates the immune system, may provide a synergistic effect, offering hope for improved outcomes in patients.

What evidence suggests that belantamab mafodotin and lenalidomide could be effective for multiple myeloma?

Research has shown that combining belantamab mafodotin with lenalidomide may effectively treat multiple myeloma, a type of blood cancer. In this trial, participants will receive belantamab mafodotin, which targets a specific protein on cancer cells and delivers a chemotherapy drug directly to them, aiding in their destruction. Studies have found that this combination can improve survival rates and is generally safe when used with other multiple myeloma treatments. Lenalidomide, also part of this trial, is already a standard treatment that helps stop cancer growth. Together, these drugs may help maintain low cancer levels in patients who have undergone a stem cell transplant. ^{1 2 5 6 7}

Who Is on the Research Team?

Jens Hillengass, MD, PhD

Principal Investigator

Roswell Park Cancer Institute

Are You a Good Fit for This Trial?

Adults diagnosed with multiple myeloma who still have minimal residual disease after a stem cell transplant can join. They should be in good enough health to perform daily activities, not pregnant or breastfeeding, and willing to use contraception. People with recent major surgery, active bleeding, severe liver conditions, certain infections like HIV or hepatitis B/C, or poor vision are excluded.

Inclusion Criteria

I am able to get out of my bed or chair and move around.

I am not pregnant or breastfeeding, and if able to have children, I agree to use contraception.

Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria

I haven't taken any experimental drugs or monoclonal antibodies recently.

I have tested positive for hepatitis C recently or had it in the past but now cleared.

I am currently pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive belantamab mafodotin IV and lenalidomide PO for 6 cycles, each cycle lasting 8 weeks

48 weeks

6 visits (in-person) for IV administration, daily oral medication

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

12 weeks

Periodic visits up to 5 years

Long-term follow-up

Participants are monitored for progression-free survival and overall survival

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Belantamab Mafodotin
• Lenalidomide

Trial Overview The trial is testing the combination of Belantamab Mafodotin (a targeted therapy) and Lenalidomide (a standard cancer treatment) on patients whose multiple myeloma isn't fully gone after a stem cell transplant. The goal is to see if this combo helps eliminate the remaining cancer cells.

How Is the Trial Designed?

Group I: Treatment (belantamab mafodotin, lenalidomide) Experimental Treatment 2 Interventions

Patients receive belantamab mafodotin IV over 30 minutes on day 1 and lenalidomide PO QD on days 1-28. Treatment repeats every 8 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity.

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?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

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 (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]

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 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]

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 the first approved therapy targeting B-cell maturation antigen (BCMA) for treating relapsed and/or refractory multiple myeloma (RRMM), specifically for patients who have undergone at least four prior therapies, addressing a significant unmet need in this patient population.

While belamaf offers a new treatment option with outpatient administration, it is associated with frequent corneal ocular adverse events, necessitating a multidisciplinary approach for patient management involving both oncologists and eye care specialists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of belantamab mafodotin for patients with relapsed and/or refractory multiple myeloma. Becnel, MR., Lee, HC.[2021]

Belantamab mafodotin (BLENREP™) is a promising new treatment for relapsed/refractory multiple myeloma, showing at least a partial response in heavily pre-treated patients, indicating its potential efficacy in difficult cases.

The treatment was well tolerated by the patients, suggesting a favorable safety profile, which is important for those who have already undergone multiple therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belantamab Mafodotin and Relapsed/Refractory Multiple Myeloma: This Is Not Game Over. Condorelli, A., Garibaldi, B., Gagliano, C., 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]

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]

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. 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 ... Moreover, in the DREAMM-8 trial, Belamaf outperformed bortezomib in combination with pomalidomide and dexamethasone. We, therefore, aimed to ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.7512

Belantamab mafodotin plus lenalidomide/dexamethasone ... We report the long-term safety & efficacy results of a novel, extended dosing schedule of belantamab mafodotin (belamaf) combined with Lenalidomide & ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2403407

Belantamab Mafodotin, Pomalidomide, and ... Data from a phase 1–2 trial involving patients with relapsed or refractory myeloma showed some safety concerns but promising clinical activity of belantamab ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11290537/

Belantamab mafodotin, lenalidomide and dexamethasone ... Preclinical and clinical data demonstrate synergy between belantamab mafodotin (belamaf) and immunomodulatory drugs with limited overlapping toxicities.

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497123113668

Long-Term Safety and Efficacy Results of Belantamab ... Part 1 evaluates the safety/tolerability of three belamaf doses (2.5/1.9/1.4 mg/kg) plus Rd in 36 pts and establishes the recommended phase 2 dose (RP2D).

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9430153/

SAFETY AND CLINICAL ACTIVITY OF BELANTAMAB ... Belamaf + LenDex had a tolerable safety profile, with no new safety signals identified in patients with RRMM. AEs, including keratopathy, were common but ...