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

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial investigates the effect of belantamab mafodotin and lenalidomide on minimal residual disease negative rates in patients with multiple myeloma with minimal residual disease positive after stem cell transplant. Belantamab mafodotin is a monoclonal antibody, called belantamab, linked to a chemotherapy drug, called mafodotin. Belantamab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as B-cell maturation antigen (BCMA) receptors, and delivers mafodotin to kill them. Lenalidomide may help block the formation of growths that may become cancer, and is used as a standard of care treatment for multiple myeloma. Giving belantamab mafodotin and lenalidomide may help to maintain minimal residual disease negativity in patients with multiple myeloma.

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.

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 studies reporting an overall response rate of about 31-34% in patients who had already undergone several other treatments. This drug was approved by the FDA based on these results, although it is associated with some eye-related side effects. ^{1 2 3 4 5}

Is the combination of Belantamab Mafodotin and Lenalidomide safe for humans?

Belantamab Mafodotin has been associated with eye-related side effects, such as changes in vision and dry eyes, which are common and sometimes severe. It is only available through a special program due to these risks. Other side effects include low platelet counts and infections, but the safety profile is considered manageable with proper monitoring. ^{1 4 5 6 7}

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

Belantamab Mafodotin is a unique drug because it is a first-in-class antibody-drug conjugate that targets a specific protein on myeloma cells, delivering a powerful cancer-killing agent directly to the cells. This approach is different from standard treatments and offers hope for patients who have already tried multiple other therapies. ^{1 2 4 8 9}

Research Team

Jens Hillengass, MD, PhD

Principal Investigator

Roswell Park Cancer Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 (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 (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 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 (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 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 (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

DREAMM-2: Indirect Comparisons of Belantamab Mafodotin vs. Selinexor + Dexamethasone and Standard of Care Treatments in Relapsed/Refractory Multiple Myeloma. [2022]

2. 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]

3. 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]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Belantamab Mafodotin and Relapsed/Refractory Multiple Myeloma: This Is Not Game Over. [2021]

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

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

6. Switzerland 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. [2023]

7. England pubmed.ncbi.nlm.nih.gov

The role of belantamab mafodotin for patients with relapsed and/or refractory multiple myeloma. [2021]

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

Belantamab Mafodotin: First Approval. [2021]

9. England pubmed.ncbi.nlm.nih.gov

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