Belantamab Mafodotin for Multiple Myeloma

Recruiting at 1 trial location

Overseen By Sara Whittington, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Pennsylvania

Must be taking: Lenalidomide

Must not be taking: Monoclonal antibodies

Disqualifiers: Amyloidosis, POEMS syndrome, 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: 1

47 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for multiple myeloma, a type of blood cancer. The study evaluates the effectiveness of belantamab mafodotin, a targeted cancer drug, administered before and after a stem cell transplant, alongside other standard treatments. It targets individuals who began treatment for multiple myeloma within the last year and have shown some improvement but not a complete response. The goal is to determine if this new approach is safe and effective compared to previous treatments. Participants should have undergone no more than two different treatment regimens and must tolerate a specific high-dose chemotherapy. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to benefit from a potentially effective new therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but you cannot have used an investigational drug or systemic anti-myeloma therapy within 14 days before starting the study drug. You also cannot have received a monoclonal antibody treatment within 28 days before the first dose.

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

Research has shown that belantamab mafodotin is approved by the FDA for treating certain cases of multiple myeloma, a type of blood cancer. This approval provides a substantial amount of safety information for its use. In other studies, belantamab mafodotin has been combined with other treatments for multiple myeloma and has proven effective when other treatments have failed.

However, like any treatment, it can cause side effects. Some patients have reported eye problems, a known side effect of belantamab mafodotin. Doctors closely monitor patients and may adjust the dose if needed to manage these issues. While the treatment can cause side effects, its FDA approval for other uses suggests it is generally considered safe. Discuss any concerns or questions with a doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple myeloma?

Belantamab mafodotin is unique because it targets and destroys myeloma cells by delivering a powerful chemotherapy agent directly to them. Unlike traditional treatments like lenalidomide or bortezomib, which broadly affect the immune system or inhibit cell growth, belantamab mafodotin uses an antibody-drug conjugate to specifically hone in on the cancer cells. This precision not only enhances the effectiveness against multiple myeloma but also reduces the collateral damage to healthy cells, potentially leading to fewer side effects. Researchers are excited about this treatment because it represents a more targeted approach, offering hope for better outcomes with less toxicity.

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

Research has shown that belantamab mafodotin effectively treats multiple myeloma that has returned or is unresponsive to other treatments. This medicine targets a protein called BCMA on myeloma cells, aiding in the destruction of cancer cells. The FDA approved belantamab mafodotin for use after other treatments have been tried, based on positive clinical trial results. Specifically, patients who did not respond to other therapies improved when treated with belantamab mafodotin. This suggests that belantamab mafodotin can be a promising option for managing multiple myeloma, especially for those with limited treatment choices. Participants in this trial will receive belantamab mafodotin as part of the study's experimental treatment arm. ^{1 2 3 6 7}

Who Is on the Research Team?

Adam Cohen, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for adults with multiple myeloma who've had no more than two prior treatments, are not in complete remission but have responded to therapy, and can undergo high-dose chemotherapy and stem cell transplant. They must be able to take maintenance therapy post-transplant and have good organ function. Pregnant or breastfeeding individuals, those with certain heart risks, infections needing antibiotics, other cancers (except if stable/treated), major surgery within the last month, active hepatitis B/C or HIV cannot join.

Inclusion Criteria

I am approved to receive a specific chemotherapy dose.

I started treatment for my multiple myeloma less than a year ago.

I've had up to 2 initial treatments for my condition without worsening.

Exclusion Criteria

I do not have active hepatitis B or I agree to preventive treatment if I have been exposed.

I do not have an infection that needs antibiotics.

I do not have an active kidney condition that could affect my safety in the trial, except for proteinuria due to MM.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-ASCT Treatment

Participants receive Belantamab mafodotin 2.5 mg/kg by intravenous infusion on day -42 relative to autologous stem cell infusion

6 weeks

1 visit (in-person)

Post-ASCT Treatment

Participants receive Belantamab mafodotin on day +60 and every 90 days thereafter, for up to 2 years following ASCT

2 years

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Belantamab mafodotin

Trial Overview The study tests Belantamab Mafodotin as an additional treatment before and after autologous stem cell transplant in multiple myeloma patients. It's given alongside standard melphalan chemotherapy pre-transplant and lenalidomide maintenance post-transplant. The goal is to see if this approach is safe and improves outcomes compared to past data.

How Is the Trial Designed?

Group I: Belantamab mafodotin Experimental Treatment 1 Intervention

Patients receive Belantamab mafodotin 2.5 mg/kg by intravenous infusion on day -42 relative to autologous stem cell infusion (day 0), on day +60, and every 90 days thereafter, for up to 2 years following ASCT.

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?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Abramson Cancer Center of the University of Pennsylvania

Lead Sponsor

Trials

360

Recruited

108,000+

Abramson Cancer Center at Penn Medicine

Lead Sponsor

Trials

425

Recruited

464,000+

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]

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 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 (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, 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]

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]

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 ... Blenrep is the only anti-BCMA accessible in the community setting where 70% of patients receive care.

2. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-belantamab-mafodotin-blmf-relapsed-or-refractory-multiple-myeloma

FDA approves belantamab mafodotin-blmf for relapsed or ... The efficacy population included 217 patients (108 and 109 in respective arms) who had received at least two prior lines of therapy, including a ...

3. ajmc.com ajmc.com/view/fda-approves-belantamab-mafodotin-combos-for-relapsed-or-refractory-multiple-myeloma

FDA Approves Belantamab Mafodotin Combo for ... - AJMC The FDA has approved belantamab mafodotin for third-line or later multiple myeloma based on DREAMM-7 trial data.

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

FDA Approves Belantamab Mafodotin Plus Bortezomib ... The FDA approved BVd for relapsed/refractory multiple myeloma after at least two prior therapies, based on DREAMM-7 trial results. BVd showed a ...

5. hematologyadvisor.com hematologyadvisor.com/news/blenrep-returns-with-new-fda-approval-in-r-r-multiple-myeloma/

Blenrep Returns With New FDA Approval in R/R Multiple ... The FDA has approved Blenrep (belantamab mafodotin-blmf) with bortezomib and dexamethasone for patients with R/R multiple myeloma who have ...

6. bloodcancerstoday.com bloodcancerstoday.com/post/fda-approves-blenrep-combo-for-relapsed-refractory-myeloma

FDA Approves Blenrep Combo for Relapsed/Refractory ... A new indication has been approved by the FDA for belantamab mafodotin-blmf (blenrep) in multiple myeloma (MM), GSK has announced.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8805802/

Belantamab Mafodotin-blmf: A Novel Antibody-Drug ... This article provides information on the mechanism of action, efficacy, safety, monitoring, and current place in therapy for belantamab mafodotin-blmf. Multiple ...