Belantamab Mafodotin for Multiple Myeloma

(DREAMM 14 Trial)

Not currently recruiting at 126 trial locations

Overseen By US GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: GlaxoSmithKline

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

Disqualifiers: Amyloidosis, POEMS syndrome, Plasma cell leukemia, 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: Unknown

Duration: Up to 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests belantamab mafodotin to determine if adjusting the dose or schedule can enhance its effectiveness and safety for individuals with relapsed or refractory multiple myeloma, a type of blood cancer. The study includes several groups receiving different doses to identify the optimal treatment balance. It seeks participants who have previously tried at least three treatments for multiple myeloma, including a stem cell transplant, without success. This trial may be suitable for those with multiple myeloma who have not responded to previous treatments. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop any systemic anti-myeloma therapy and high-dose steroids at least 14 days before starting the study treatment. If you have been treated with a monoclonal antibody, you must wait 30 days before the first dose of the study treatment.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research has shown that the FDA approves belantamab mafodotin for treating relapsed or refractory multiple myeloma. This approval indicates that testing has confirmed its safety and effectiveness for this condition. Studies have found that it can cause side effects like vision changes and low blood cell counts, but regular check-ups and care usually manage these. Participants in previous trials generally tolerated the treatment well, with doctors closely monitoring any issues. Prospective trial participants should discuss any concerns with their doctor to determine if it's the right choice. ^{1 2 3 4 5}

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

Belantamab mafodotin is unique because it employs an innovative approach to treating multiple myeloma by targeting the B-cell maturation antigen (BCMA) on cancer cells. Unlike traditional therapies like proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, belantamab mafodotin combines an antibody with a cytotoxic agent, delivering a powerful punch directly to the cancer cells. Researchers are excited about this treatment because it offers a new mechanism of action that could potentially overcome resistance seen with existing therapies, providing hope for patients with relapsed or refractory multiple myeloma.

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

Research has shown that belantamab mafodotin can help treat relapsed or refractory multiple myeloma, a type of blood cancer. In earlier studies, patients who had already tried at least two other treatments responded well to belantamab mafodotin. This trial will explore different dosing levels of belantamab mafodotin, with participants assigned to various cohorts receiving different dose levels. The treatment targets a specific protein on myeloma cells, aiding in their destruction. Although concerns exist about side effects related to the eyes, the FDA has approved belantamab mafodotin for certain cases. This approval is based on evidence that it can be effective when other treatments have not worked. ^{2 6 7 8 9}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Are You a Good Fit for This Trial?

This trial is for adults with relapsed or refractory multiple myeloma who have tried at least three prior treatments, including specific antibody and inhibitor therapies. They must be in relatively good health (ECOG 0-2), not pregnant, willing to use contraception, and without serious liver, kidney, bleeding disorders or other severe conditions that could affect safety.

Inclusion Criteria

You have a detectable disease according to specific criteria.

I can take care of myself and am up and about more than half of my waking hours.

I have MM, failed 3 treatments including CD38 antibody, and can't have or failed a stem cell transplant.

Exclusion Criteria

Your white blood cell count is very low, or your platelet count is very low.

I do not have cirrhosis or current unstable liver or biliary disease.

I am currently on medication for an infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive various dosing regimens of belantamab mafodotin to evaluate safety, efficacy, and pharmacokinetics

Up to 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Belantamab mafodotin

Trial Overview The study tests different doses and schedules of belantamab mafodotin to find a better balance between benefits and risks for patients with multiple myeloma. It's only for those whose disease has returned after treatment or didn't respond to previous therapies.

How Is the Trial Designed?

Group I: Cohort 5: Participants receiving belantamab mafodotin at DL4 with alternative dose modification Experimental Treatment 1 Intervention

Group II: Cohort 4: Participants receiving belantamab mafodotin at DL 4 Experimental Treatment 1 Intervention

Group III: Cohort 3: Participants receiving belantamab mafodotin at DL 3 Experimental Treatment 1 Intervention

Group IV: Cohort 2: Participants receiving belantamab mafodotin at DL 2 Experimental Treatment 1 Intervention

Group V: Cohort 1: Participants receiving belantamab mafodotin at dose level (DL) 1 Experimental Treatment 1 Intervention

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?

GlaxoSmithKline

Lead 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 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) 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 (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 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 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 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]

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

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

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

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

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. us.gsk.com us.gsk.com/en-us/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 ... Interim efficacy and safety data for Blenrep as a first line treatment are expected in early 2028 with enrollment expanded to US sites to ...

7. cancertherapyadvisor.com cancertherapyadvisor.com/news/fda-approves-blenrep-for-relapsed-or-refractory-multiple-myeloma/

FDA Approves Blenrep for Relapsed or Refractory Multiple ... Triplet combination treatment shows 51 percent reduction in the risk for death and tripled median progression-free survival versus a ...

8. medchemexpress.com medchemexpress.com/belantamab-mafodotin.html?srsltid=AfmBOopw5P_usTpQD-ls8NyJHaMd9bWufF2U9qhrH5r9rKTqJXA-LmsU

Belantamab mafodotin (GSK2857916) | Anti-BCMA ADC Belantamab mafodotin induces G2/M arrest in multiple myeloma cells in a dose and time dependent manner. Belantamab mafodotin signifcantly promotes phagocytosis ...

9. myeloma.org myeloma.org/blenrep-belantamab-mafodotin-blmf

BLENREP (belantamab mafodotin-blmf) Blenrep (belantamab mafodotin-blmf) is an antibody-drug conjugate (ADC), the first in a new class of treatments for myeloma.