Belantamab Mafodotin for Multiple Myeloma

(COSTA Trial)

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

33 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a research study to find out if a drug called belantamab mafodotin in combination with dexamethasone, a steroid, can be safely and effectively given in the community setting. Belantamab mafodotin (BLENREP) was approved in the US in August 2020 under an FDA program called accelerated approval. In November 2022, belantamab mafodotin was removed from the market because a study to further confirm its activity in relapsed/refractory multiple myeloma did not deliver a supporting result. However, this confirmatory study demonstrated that some patients may still benefit from treatment with belantamab mafodotin, and that this benefit can be long lasting. Belantamab mafodotin is often given at large academic medical centers every 3 weeks. This study will assess whether it is possible to administer belantamab in the community setting every 6 weeks. It is unknown if administering belantamab every 6 weeks versus every 3 weeks will result in improved safety and/or reduced efficacy.

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.

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 a 32% overall response rate in patients who had already undergone several treatments, as demonstrated in the DREAMM-2 study. It works by targeting and killing myeloma cells, and has been approved for use in patients who have tried at least four other therapies. ^{1 2 3 4 5}

Is Belantamab Mafodotin safe for humans?

Belantamab Mafodotin has shown manageable safety in clinical trials for multiple myeloma, but it can cause significant eye-related side effects like keratopathy (damage to the cornea) and blurred vision, as well as low platelet counts (thrombocytopenia). It is approved for use with a warning for these side effects and is available only through a restricted program to ensure safe use. ^{2 3 6 7 8}

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

Belantamab Mafodotin is unique because it is a first-in-class antibody-drug conjugate that targets BCMA on myeloma cells, delivering a powerful cancer-killing agent directly to the cells. This targeted approach allows it to be effective in patients who have already tried multiple other treatments. ^{1 2 3 4 6}

Research Team

Cristiana Costa Chase, DO

Principal Investigator

Duke Health

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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, 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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

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

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

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

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

Belantamab Mafodotin: First Approval. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study. [2020]

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

Exposure-Response Analyses for Therapeutic Dose Selection of Belantamab Mafodotin in Patients With Relapsed/Refractory Multiple Myeloma. [2022]

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

Real-world experience with belantamab mafodotin therapy for relapsed/refractory multiple myeloma: A multicentre retrospective study. [2023]

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

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