What is the mechanism of action of this treatment?

Belantamab Mafodotin is an antibody-drug conjugate that targets B-cell maturation antigen (BCMA) on myeloma cells, delivering a cytotoxic agent directly to the cancer cells, thereby reducing tumor burden. Nirogacestat is a gamma-secretase inhibitor that prevents the cleavage of BCMA from the surface of myeloma cells, enhancing the efficacy of BCMA-targeted therapies. Pomalidomide is an immunomodulatory drug that enhances the immune system's ability to attack myeloma cells and inhibits their growth. These mechanisms are crucial for Multiple Myeloma patients as they offer targeted approaches to reduce cancer cell proliferation and improve patient outcomes, especially in cases where the disease is refractory or has relapsed after initial treatments.

What side effects are associated with this type of intervention?

Common treatments for Multiple Myeloma similar to those in the trial include Belantamab Mafodotin, which can cause ocular toxicity, thrombocytopenia, and infusion-related reactions. Pomalidomide, an immunomodulatory drug, is associated with neutropenia, infections (such as pneumonia and urinary tract infections), and venous thromboembolism. While specific side effects of Nirogacestat are not detailed, gamma-secretase inhibitors can potentially cause gastrointestinal issues and fatigue. Overall, these treatments can lead to a range of hematologic and non-hematologic toxicities, necessitating careful monitoring.

What prior FDA approvals exist?

Belantamab mafodotin is the first anti-BCMA therapy approved by the FDA for relapsed/refractory multiple myeloma. Pomalidomide, an immunomodulatory drug, is also FDA-approved for multiple myeloma, particularly in patients who have received at least two prior therapies including lenalidomide and a proteasome inhibitor. Other notable FDA-approved treatments include bortezomib (a proteasome inhibitor), lenalidomide (another immunomodulatory drug), and daratumumab (a monoclonal antibody targeting CD38). These approvals highlight the evolving landscape of targeted therapies in multiple myeloma treatment.

What other types of research exist?

Promising novel alternatives for Multiple Myeloma treatment in 2024 include: <ol> <li>Isatuximab (Anti-CD38 Monoclonal Antibody)</li> <li></li> </ol> Marizomib (Proteasome Inhibitor) 3. Venetoclax (BCL-2 Inhibitor) 4. Selinexor (Selective Inhibitor of Nuclear Export) 5. Carfilzomib (Proteasome Inhibitor) in combination with other agents like Daratumumab (Anti-CD38 Monoclonal Antibody) and Dexamethasone.

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Monoclonal Antibodies

Belantamab Mafodotin + Nirogacestat + Pomalidomide for Multiple Myeloma

Phase 1

Recruiting

Led By Malin Hultcrantz, MD, PhD

Research Sponsored by Memorial Sloan Kettering Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients with relapsed or refractory multiple myeloma treated with 3 or more prior lines of therapy as defined by the International Myeloma Working Group (IMWG) updated criteria

Female or male patients age ≥18 years

Must not have

Current active liver or biliary disease

Participants with invasive malignancies other than multiple myeloma

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Awards & highlights

Summary

This trial is testing the safety and efficacy of two drugs, belantamab mafodotin and nirogacestat, for people with relapsed or refractory multiple myeloma.

Who is the study for?

This trial is for adults with multiple myeloma that hasn't improved or has returned after treatment. Participants must have measurable disease, may have had a stem cell transplant or be ineligible for one, and should not have major health issues that could affect safety. They need to agree to contraception use and follow specific drug safety programs.Check my eligibility

What is being tested?

Researchers are testing the combination of belantamab mafodotin, nirogacestat, and pomalidomide on patients with relapsed or refractory multiple myeloma. They aim to determine the safest doses and effectiveness in slowing down or stopping cancer growth.See study design

What are the potential side effects?

Potential side effects include eye problems like blurry vision due to corneal changes, blood disorders such as low platelet counts leading to bleeding risks, fatigue, digestive issues including nausea and constipation, increased risk of infections due to immune system effects.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have multiple myeloma and have undergone 3 or more treatments.

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I am 18 years old or older.

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My cancer can be measured by blood tests, urine tests, imaging, or biopsy.

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I have had a stem cell transplant using my own cells or am not eligible for one.

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I have previously received CAR T cell therapy.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have an active liver or biliary disease.

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I have a cancer type other than multiple myeloma.

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I am currently experiencing bleeding from an internal organ or mucosa.

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I had a stem cell transplant less than 60 days ago if it was my own cells, or less than 100 days ago if it was from a donor.

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I have been treated with belantamab mafodotin before.

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I haven't had any myeloma treatment or plasmapheresis in the last 2 weeks.

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I have an active kidney condition.

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I have a condition that affects how my body absorbs nutrients.

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I have not had radiation therapy in the last 2 weeks.

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I am currently being treated for an infection.

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I have been diagnosed with AL amyloidosis.

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I have a disease affecting my cornea.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 years for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

Number of Participants who Experienced Dose-Limiting Toxicities (DLTs)

Secondary outcome measures

Clinical Response

Trial Design

1Treatment groups

Experimental Treatment

Group I: Belantamab Mafodotin and NirogacestatExperimental Treatment3 Interventions

There will be a 1:1 randomization betweennirogacestat 100 mg BID or 100 mg QD during the 4day run-in period prior to starting belantamab mafodotin on Cycle 1 Day 1 (days -4 to -1). The cycle length for Cycles 1-3 is 21 days (3 weeks). Treatment with nirogacestat will be 100 mg BID continuously during each cycle for all subjects. Belantamab mafodotin will be administered via IV infusion in an outpatient setting on Day 1 of Cycles 1-3 and nirogacestat 100mg BID will be administered continuously on Days 1-21 of each cycle. Treatment with belantamab mafodotin will be given at an initial dose of 1.0 mg/kg. The study will have a 3+3 dose escalation design for belantamab mafodotin. Belantamab mafodotin dose levels are 1.0 mg/kg, 1.4 mg/kg, and 1.9 mg/kg. Pomalidomide was added, 2 mg to the 1.4 mg/kg and 1.9 mg/kg dose cohorts.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Belantamab Mafodotin

2021

Completed Phase 2

~10

Pomalidomide

2011

Completed Phase 2

~1020

0 / 17Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Belantamab Mafodotin is an antibody-drug conjugate that targets B-cell maturation antigen (BCMA) on myeloma cells, delivering a cytotoxic agent directly to the cancer cells, thereby reducing tumor burden. Nirogacestat is a gamma-secretase inhibitor that prevents the cleavage of BCMA from the surface of myeloma cells, enhancing the efficacy of BCMA-targeted therapies. Pomalidomide is an immunomodulatory drug that enhances the immune system's ability to attack myeloma cells and inhibits their growth. These mechanisms are crucial for Multiple Myeloma patients as they offer targeted approaches to reduce cancer cell proliferation and improve patient outcomes, especially in cases where the disease is refractory or has relapsed after initial treatments.

B-cell maturation antigen (BCMA) in multiple myeloma: the new frontier of targeted therapies.Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study.