Belantamab + Elotuzumab for Multiple Myeloma

Overseen By Carole Ramm

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Yale University

Must be taking: iMID, proteasome inhibitor

Must not be taking: Monoclonal antibodies

Disqualifiers: Corneal disease, Liver disease, Renal condition, Cardiovascular risk, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 32

Duration: Up to 2 years

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining two drugs, belantamab mafodotin and elotuzumab, can safely and more effectively treat multiple myeloma, a type of blood cancer. Both drugs are already used separately for this condition, but researchers aim to determine if their combined use offers better results. The trial seeks participants whose multiple myeloma has returned or hasn't responded after at least three different treatments. Those who have faced frequent relapses or resistant forms of multiple myeloma might find this trial suitable. As a Phase 1/Phase 2 trial, the study focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering a chance to contribute to groundbreaking research.

Do I need to stop my current medications to join the trial?

The protocol does not specify if you need to stop your current medications. However, you must not have used an investigational drug or approved systemic anti-myeloma therapy within 14 days before the first dose, and you must not have received a monoclonal antibody within 30 days of the first dose. Systemic steroids are allowed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that combining belantamab mafodotin and elotuzumab is generally safe and well-tolerated by patients. Earlier studies have provided promising results, indicating that these drugs can be safely combined.

The FDA has approved belantamab mafodotin for treating relapsed or refractory multiple myeloma, based on its proven safety and effectiveness. Elotuzumab is also approved for multiple myeloma and has been safely used in various treatments.

While both drugs are approved for individual use, this trial tests them together. So far, the combination has proven safe, with no unexpected severe side effects reported in early research. However, like all treatments, some side effects may occur, which the trial aims to understand better. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Belantamab mafodotin and Elotuzumab for multiple myeloma because they offer novel mechanisms of action compared to current treatments like proteasome inhibitors and immunomodulatory drugs. Belantamab mafodotin is an antibody-drug conjugate that specifically targets the BCMA protein on myeloma cells, delivering a cell-killing agent directly to the cancer cells. Elotuzumab, on the other hand, works by activating the immune system to attack myeloma cells by targeting the SLAMF7 protein. These approaches provide a fresh angle for tackling multiple myeloma, potentially leading to more effective treatments with targeted action.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

In a previous study, belantamab mafodotin helped 45% of patients with relapsed or hard-to-treat multiple myeloma. On average, these patients lived without disease progression for 3.8 months and had a total survival of 17.2 months. Elotuzumab, another treatment, has already shown effectiveness when combined with other drugs against multiple myeloma. This trial will evaluate the combination of belantamab mafodotin and elotuzumab, which research suggests might enhance their effectiveness. Early results indicate this combination is safe and could lead to better outcomes. ^{1 2 3 4 6}

Who Is on the Research Team?

Natalia Neparidze, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with multiple myeloma that's come back or hasn't responded to at least three prior treatments. They must have decent organ function, not be pregnant, and agree to use contraception. People can't join if they've had recent major surgery, active infections needing IV treatment, certain eye diseases, unstable heart conditions, or used other investigational drugs recently.

Inclusion Criteria

I have been treated with iMID and proteasome inhibitors before.

My multiple myeloma has not responded to at least 3 previous treatments.

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

Exclusion Criteria

I have not undergone plasmapheresis in the last 7 days.

I do not have any serious eye surface diseases.

I have not had major surgery in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive belantamab mafodotin and elotuzumab. Elotuzumab is administered at 10 mg/kg on days 1, 8, 15, 22 every 28 days for cycles 1 and 2, followed by 20 mg/kg on day 1 of each cycle thereafter. Belantamab mafodotin is administered at 1.9 mg/kg every 4 weeks, with possible dose adjustments.

Up to 2 years

4 visits per cycle (in-person)

Follow-up

Participants are monitored for progression-free survival and overall survival, with evaluations including MM labs and bone marrow biopsy.

Up to 2 years

Every 28 days until progression

Extension

Participants may continue to be monitored for overall survival and minimal residual disease by multi-parameter flow cytometry and next-generation sequencing.

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Belantamab mafodotin
• Elotuzumab

Trial Overview The study tests the combination of two approved drugs for multiple myeloma—Belantamab Mafodotin and Elotuzumab—to see if they work better together. Participants will receive both medications under controlled conditions to assess safety and effectiveness.

How Is the Trial Designed?

Group I: Belantamab Mafodotin and Elotuzumab Arm Experimental Treatment 2 Interventions

Elotuzumab will be administered via intravenous infusion at an established dose of 10 mg/kg on days 1, 8, 15, 22 every 28 days for cycles 1 and 2, followed by 20mg/kg on day 1 of each cycle thereafter, cycles repeated every 28 days. Belantamab mafodotin will be administered via IV infusion. There will be 3 dose levels for belantamab mafodotin, with the starting dose of 1.9 mg/kg IV at every 4 week interval. Up to 12 subjects will be treated at this dose level. If the initial dose is found to be too toxic, dose of belantamab mafodotin 1.9 mg/kg every 8 weeks will be tested, further dose reduction to 1.4mg/kg every 8 weeks will be administered.

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?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

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 (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 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 (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 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 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]

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 (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]

In a study of 27 triple-class refractory multiple myeloma patients, the anti-BCMA monoclonal antibody belantamab mafodotin demonstrated an overall response rate of 52% and a disease control rate of 70%, indicating its effectiveness in a challenging patient population.

The most common side effect was eye toxicity, affecting 44% of patients, with 33.3% experiencing moderate to severe keratopathy, highlighting the need for monitoring eye health during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Effectiveness and Safety of Belantamab Mafodotin Monotherapy in Triple-Class Refractory Multiple Myeloma. Ntanasis-Stathopoulos, I., Malandrakis, P., Fotiou, D., et al.[2023]

Citations

1. yalemedicine.org yalemedicine.org/clinical-trials/novel-combination-of-belantamab-mafodotin-and-elotuzumab-to-enhance-therapeutic-efficacy-in-multiple

Novel Combination of Belantamab Mafodotin and ... The purpose of this research study is to determine if two drugs approved for treating multiple myeloma, belantamab mafodotin and elotuzumab, are safe and more ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05002816

Study Details | NCT05002816 | Novel Combination of ... The purpose of this research study is to determine if two drugs approved for treating multiple myeloma, belantamab mafodotin and elotuzumab, are safe and more ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.7559

Open-label, single-arm phase Ib/II study of immune ... This novel combination immune therapy with belantamab mafodotin and elotuzumab appears to have an encouraging safety profile and a promising preliminary ...

4. ashpublications.org ashpublications.org/bloodneoplasia/article/2/3/100103/536762/Belantamab-mafodotin-in-patients-with-relapsed

Belantamab mafodotin in patients with relapsed/refractory ... Belantamab mafodotin showed ORR 45%, PFS 3.8 months, and OS 17.2 months in relapsed/refractory multiple myeloma in a real-world setting.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10251850/

Belantamab Mafodotin: From Clinical Trials Data to Real-Life ... Results from subcutaneous teclistamab, a T-cell redirecting bispecific antibody targeting BCMA, showed an impressive overall response rate (ORR) of 73% in ...

6. myeloma.org myeloma.org/news-events/multiple-myeloma-news/fda-approves-blenrep-rrmm

U.S. FDA Approves Blenrep for the Treatment of Relapsed/ ... U.S. FDA approves Blenrep® (belantamab mafodotin-blmf) for the treatment of relapsed/refractory multiple myeloma.