Belantamab Mafodotin Combinations for Multiple Myeloma

(DREAMM5 Trial)

Not currently recruiting at 63 trial locations

Overseen By EU GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: GlaxoSmithKline

Must not be taking: Monoclonal antibodies, CYP3A4 inhibitors

Disqualifiers: Corneal disease, Cardiovascular risk, Infection, 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 a new treatment option, belantamab mafodotin, for patients with multiple myeloma, a type of blood cancer that has recurred or is difficult to treat. Researchers combine this drug with other cancer medications to evaluate the effectiveness of these combinations. The trial is divided into different parts to explore various drug combinations. Individuals who have previously undergone multiple myeloma treatments, including certain medicines and a stem cell transplant, 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.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had other monoclonal antibodies within 30 days or systemic anti-myeloma therapy within 14 days before starting the study. Also, certain HIV drugs are restricted if you are receiving nirogacestat. It's best to discuss your specific medications with the trial team.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have had other monoclonal antibodies within 30 days or systemic anti-myeloma therapy within 14 days before starting the study. It's best to discuss your specific medications with the trial team.

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

Research has shown that belantamab mafodotin presents some safety concerns based on previous studies. The FDA has approved it for treating relapsed or refractory multiple myeloma, but it has known side effects. The most significant issue involves eye problems, particularly affecting the clear front layer of the eye. Other safety concerns include a low platelet count and infusion-related reactions.

Despite these concerns, many patients who have undergone several treatments have used belantamab mafodotin safely, demonstrating its effectiveness in such cases. However, anyone considering joining a trial should be aware of these potential side effects and discuss them with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Belantamab mafodotin is unique because it targets the B-cell maturation antigen (BCMA) on multiple myeloma cells, which is different from standard therapies like proteasome inhibitors or immunomodulatory drugs. Researchers are excited about its potential because it delivers a potent cell-killing agent directly to cancer cells, minimizing damage to healthy cells. Additionally, in combination with other novel agents like nirogacestat or dostarlimab, it could enhance efficacy by disrupting cancer cell survival pathways or boosting immune response, offering hope for improved outcomes in patients with this challenging condition.

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

Studies have shown that belantamab mafodotin effectively treats relapsed or refractory multiple myeloma, a type of blood cancer. Some research found it lowers the risk of death by 51% and triples the time patients live without their cancer worsening. Early results indicate that belantamab mafodotin benefits about 32% of patients, with nearly one-third experiencing cancer shrinkage or halted growth. The FDA has approved it for patients who have not succeeded with other treatments. This trial will explore various combinations of belantamab mafodotin with other drugs, such as nirogacestat, lenalidomide, pomalidomide, and dexamethasone, to assess their effectiveness in treating multiple myeloma. These findings suggest belantamab mafodotin could be a promising option for those facing this challenging condition. ^{2 4 6 7 8}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Are You a Good Fit for This Trial?

Adults with a confirmed diagnosis of Multiple Myeloma who have tried at least three prior treatments, including an immunomodulating agent and a proteasome inhibitor. They must have measurable disease, be in good physical condition (ECOG 0-1), and not have had certain recent treatments or uncontrolled diseases. Specific criteria apply for participants from Japan and China.

Inclusion Criteria

Participants with contraception requirements specific to Sub-study 6, 7, and 8 respectively.

I tested positive for Hepatitis B core antibody but do not have active Hepatitis B.

I am currently taking low-dose oral steroids, inhaled steroids, or eye steroids.

Exclusion Criteria

I received CAR-T therapy with chemotherapy less than 3 months ago.

I stopped a previous cancer treatment due to severe side effects.

I have low levels of phosphate, potassium, or magnesium that don't improve with treatment.

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 other anti-cancer drugs

Up to 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 36 months

What Are the Treatments Tested in This Trial?

Interventions

• Belantamab mafodotin

Trial Overview The trial is testing Belantamab Mafodotin alone or combined with other anti-cancer drugs in those with relapsed/refractory Multiple Myeloma. It's an open-label study where different drug combinations are tested simultaneously to see how well they work.

How Is the Trial Designed?

Group I: Belantamab mafodotin+nirogacestat dose exploration(Sub-study 3) Experimental Treatment 2 Interventions

Group II: Belantamab mafodotin+isatuximab dose exploration (Sub-study 5) Experimental Treatment 2 Interventions

Group III: Belantamab mafodotin+feladilimab dose exploration (Sub-study 2) Experimental Treatment 2 Interventions

Group IV: Belantamab mafodotin+dostarlimab dose exploration(Sub-study 4) Experimental Treatment 2 Interventions

Group V: Belantamab mafodotin+GSK3174998 dose exploration (Sub-study 1) Experimental Treatment 2 Interventions

Group VI: Belantamab mafodotin+GSK3174998 cohort expansion (Sub-study 1) Experimental Treatment 2 Interventions

Group VII: Belantamab mafodotin+ nirogacestat+ pomalidomide + dexamethasone dose exploration (Sub-study 7) Experimental Treatment 4 Interventions

Group VIII: Belantamab mafodotin+ nirogacestat+ pomalidomide + dexamethasone cohort expansion (Sub-study 7) Experimental Treatment 4 Interventions

Group IX: Belantamab mafodotin+ nirogacestat+ lenalidomide+ dexamethasone dose exploration (Sub-study 8) Experimental Treatment 4 Interventions

This cohort will enroll Northeast Asian participants.

Group X: Belantamab mafodotin+ nirogacestat+ lenalidomide+ dexamethasone dose exploration (Sub-study 6) Experimental Treatment 4 Interventions

Group XI: Belantamab mafodotin+ nirogacestat+ lenalidomide+ dexamethasone cohort expansion (Sub-study 8) Experimental Treatment 4 Interventions

This cohort will enroll Northeast Asian participants.

Group XII: Belantamab mafodotin+ nirogacestat+ lenalidomide+ dexamethasone cohort expansion (Sub-study 6) Experimental Treatment 4 Interventions

Group XIII: Belantamab mafodotin+ nirogacestat cohort expansion (Sub-study 3) Experimental Treatment 2 Interventions

Group XIV: Belantamab mafodotin+ isatuximab cohort expansion (Sub-study 5) Experimental Treatment 2 Interventions

Group XV: Belantamab mafodotin+ feladilimab cohort expansion (Sub-study 2) Experimental Treatment 2 Interventions

Group XVI: Belantamab mafodotin+ dostarlimab cohort expansion (Sub-study 4) Experimental Treatment 2 Interventions

Group XVII: Belantamab mafodotin monotherapy cohort expansion Active Control 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 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]

Pharmacogenomic studies have identified specific genetic markers, such as certain HLA alleles, that are strongly associated with severe adverse drug reactions (ADRs), which can help predict and prevent these unpredictable reactions in patients.

Understanding these genetic markers can lead to personalized medicine approaches, allowing healthcare providers to avoid prescribing drugs that may cause severe ADRs based on a patient's genetic profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Updated Review of Genetic Associations With Severe Adverse Drug Reactions: Translation and Implementation of Pharmacogenomic Testing in Clinical Practice. Wang, CW., Preclaro, IAC., Lin, WH., 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]

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]

The incidence of idiosyncratic drug-induced agranulocytosis has remained stable at 2.4-15.4 cases per million over the past 20 years, despite the introduction of new drugs, indicating a consistent risk associated with various medications.

With proper management, including the use of broad-spectrum antibiotics and hematopoietic growth factors, the mortality rate for patients experiencing this serious adverse event has decreased to around 5%, highlighting the importance of timely and effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Idiosyncratic drug-induced agranulocytosis: Update of an old disorder. Andrès, E., Zimmer, J., Affenberger, S., et al.[2006]

In a study of 453 inflammatory bowel disease patients, none of the 78 patients with G6PD deficiency experienced acute hemolytic anemia while taking mesalamine, suggesting it is safe for this group.

Chronic hemolysis markers did not show significant differences between G6PD deficient patients and controls, indicating that mesalamine does not pose a risk of hemolysis at doses up to 4500 mg/day.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of Hemolytic Anemia in IBD Patients with Glucose-6-Phosphate Dehydrogenase Deficiency Treated with Mesalamine: Results of a Retrospective-Prospective and Ex Vivo Study. Dore, MP., Tomassini, G., Rocchi, C., et al.[2023]

In a review of 66 studies involving 8,302 patients with inflammatory bowel disease, the cumulative incidence of myelosuppression from azathioprine (AZA) and mercaptopurine (MP) was found to be 7%, with an annual incidence rate of about 3%.

Severe myelotoxicity occurred in less than 1% of patients per year, and the risk of death due to myelotoxicity was very low, at approximately 0.06%, indicating that while myelosuppression is a serious concern, it is relatively rare in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thiopurine-induced myelotoxicity in patients with inflammatory bowel disease: a review. Gisbert, JP., Gomollón, F.[2017]

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 (BM) demonstrated a 42.2% overall response rate in patients with triple-class relapsed and refractory multiple myeloma, indicating significant anti-myeloma activity in a real-world setting with 33 patients studied over an 11-month median follow-up.

The safety profile of BM was manageable, with 57.6% of patients experiencing non-hematological treatment-emergent adverse events, primarily keratopathy, which resolved in 70.6% of cases, suggesting that while side effects occurred, they were often reversible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Outcomes of Belantamab Mafodotin for Relapsed/Refractory Multiple Myeloma (RRMM): Preliminary Results of a Spanish Expanded Access Program (EAP). Alegre, A., Benzo, G., Alonso, R., 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]

GSK2857916 (belantamab mafodotin) effectively targets BCMA in multiple myeloma, inducing immunogenic cell death and enhancing immune cell activation, which leads to delayed tumor growth and complete regressions in mice.

The treatment not only promotes an adaptive immune response but also shows potential for improved outcomes when combined with immune agonists, suggesting a promising avenue for future clinical trials in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belantamab Mafodotin (GSK2857916) Drives Immunogenic Cell Death and Immune-mediated Antitumor Responses In Vivo. Montes de Oca, R., Alavi, AS., Vitali, N., et al.[2023]

Agranulocytosis, a serious condition where white blood cell counts drop dangerously low, was reported in 100 cases as probable and in 78 cases as possible among 425 drug-related reports analyzed from 1974 to 1994.

The drugs most frequently associated with agranulocytosis included dipyrone, mianserin, and sulphasalazine, highlighting the importance of monitoring these medications for potential severe side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug-associated agranulocytosis: 20 years of reporting in The Netherlands (1974-1994). van der Klauw, MM., Wilson, JH., Stricker, BH.[2019]

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. nature.com nature.com/articles/s41408-025-01226-8

A real-world experience of efficacy and safety ... In summary, belantamab mafodotin appeared safe and relatively effective in this real-world heavily pretreated RRMM population, where the ...

3. healio.com healio.com/news/hematology-oncology/20251024/blenrep-rebounds-after-fda-setback-with-approval-for-relapsed-refractory-multiple-myeloma

FDA OK's belantamab mafodotin-blmf for multiple myeloma Results showed that the belantamab mafodotin-blmf regimen reduced risk for death by 51% (HR = 0.49; 95% CI, 0.32-0.76) and tripled median ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265025001387

Treatment Patterns, Efficacy, and Tolerability of ... At 13-month follow-up, overall response rate (ORR) was 32%, median progression-free survival (PFS) 2.8 months, median duration of response (DOR) 11.0 months, ...

5. 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 ... Efficacy was established based on progression-free survival (PFS) and overall survival (OS). The median PFS was 31.3 months (95% confidence ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2020/761158s000lbl.pdf

Blenrep (belantamab mafodotin-blmf) - accessdata.fda.gov WARNING: OCULAR TOXICITY. See full prescribing information for complete boxed warning. ○ BLENREP caused changes in the corneal epithelium resulting in.

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

BLENREP (belantamab mafodotin-blmf) U.S. FDA Approves Blenrep for the Treatment of Relapsed/Refractory Multiple Myeloma ... The approval is supported by data from the phase III DREAMM-7 trial. Visit ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9633344/

FDA Approval Summary: Belantamab Mafodotin for ... Key safety concerns for belantamab mafodotin include ocular toxicity, thrombocytopenia, and infusion-related reactions. • The ocular toxicity observed with ...