Belantamab Mafodotin for Multiple Myeloma

(COSTA Trial)

Not yet recruiting at 4 trial locations

Overseen By Maria Fochesato, RN, OCN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Cristiana Costa Chase, DO

Must not be taking: Systemic steroids, Monoclonal antibodies

Disqualifiers: Corneal disease, Liver disease, Cardiovascular, 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: 6

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether belantamab mafodotin (an anti-cancer drug), combined with the steroid dexamethasone, can be safely and effectively administered to multiple myeloma patients in community settings every six weeks instead of the usual three weeks. Multiple myeloma is a type of blood cancer, and the trial aims to determine if this new schedule could offer similar or better benefits. Individuals who have undergone multiple treatments for multiple myeloma and whose disease has not responded to other therapies might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have used an investigational drug or approved systemic anti-myeloma therapy within 14 days before the study, and you must not have received a monoclonal antibody treatment within 30 days before the study.

Is there any evidence suggesting that belantamab mafodotin in combination with dexamethasone is likely to be safe?

Research has shown that belantamab mafodotin was studied for treating multiple myeloma, a type of blood cancer. The FDA approved this drug for the condition, but it was later removed from the market because a follow-up study did not support its continued use.

Regarding safety, earlier studies found that all patients experienced some side effects from this medication. Most patients had serious side effects, such as low blood cell counts and eye problems. Despite these risks, some patients benefited from the treatment.

Researchers are now exploring whether administering belantamab mafodotin every six weeks, instead of every three weeks, might be safer or still effective. Although the drug was removed from the market, this research could help determine if it can be used safely in a different way. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for multiple myeloma?

Belantamab mafodotin is unique because it introduces a novel approach to treating multiple myeloma by utilizing an antibody-drug conjugate. Unlike standard treatments like proteasome inhibitors or immunomodulatory drugs, belantamab mafodotin specifically targets and binds to the B-cell maturation antigen (BCMA) on myeloma cells, delivering a potent chemotherapy agent directly into the cancer cell. This targeted delivery method not only enhances the drug's effectiveness but also aims to minimize damage to healthy cells, potentially reducing side effects. Researchers are excited because this targeted approach could offer new hope for patients who have become resistant to existing therapies.

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

Research has shown that belantamab mafodotin, also known as BLENREP, can effectively treat relapsed or refractory multiple myeloma, a type of blood cancer. This drug targets a protein called BCMA on cancer cells, aiding the immune system in attacking them. Some studies found that patients experienced long-lasting benefits from this treatment. Although it was removed from the market for not meeting certain study results, it still demonstrated potential benefits for some patients. In this trial, participants will receive belantamab mafodotin every six weeks to explore whether it can be safely administered less frequently in local healthcare settings. ^{1 2 3 4 6}

Who Is on the Research Team?

Cristiana Costa Chase, DO

Principal Investigator

Duke Health

Are You a Good Fit for This Trial?

Adults with a confirmed diagnosis of multiple myeloma who have tried at least four prior therapies and are resistant to certain drugs can join. They must be in good overall health, not wear contact lenses (due to eye exams required by the study), and use effective contraception. People with active infections, unstable heart or liver conditions, recent major surgery, or those on other clinical trials without approval cannot participate.

Inclusion Criteria

Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent

I have multiple myeloma, tried at least 4 treatments, and didn't respond to specific drugs.

All my side effects from previous treatments are mild or stable for 6 weeks.

Exclusion Criteria

I do not have an active kidney condition.

Participant must not have any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures

Participant must not be simultaneously in any other therapeutic clinical trial without permission of the Sponsor

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive belantamab mafodotin in combination with dexamethasone every 6 weeks

48 weeks

Every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Belantamab mafodotin

Trial Overview The trial is testing belantamab mafodotin combined with dexamethasone for relapsed/refractory multiple myeloma patients in a community setting every 6 weeks instead of the usual 3-week cycle. The aim is to see if this new schedule improves safety or affects effectiveness.

How Is the Trial Designed?

Group I: Treatment every 6 weeks Experimental Treatment 1 Intervention

Treatment every 6 weeks

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?

Cristiana Costa Chase, DO

Lead Sponsor

Trials

1

Recruited

30+

Published Research Related to This Trial

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 (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 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, 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) 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 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. cancernetwork.com cancernetwork.com/view/fda-approves-belantamab-mafodotin-in-r-r-multiple-myeloma

FDA Approves Belantamab Mafodotin in R/R Multiple ... Belantamab mafodotin has been approved for multiple myeloma despite the FDA's ODAC committee voting against the treatment due to ocular ...

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.