Belantamab Mafodotin + Pomalidomide + Dexamethasone for Multiple Myeloma

Overseen By Ajay K. Nooka, MD,MPH,FACP

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Must not be taking: Monoclonal antibodies, Systemic steroids

Disqualifiers: Corneal disease, Liver disease, Renal condition, 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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 3 years

34 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies the effect of belantamab mafodotin, pomalidomide, and dexamethasone in treating patents with high-risk myeloma. Belantamab mafodotin is a monoclonal antibody, called belantamab, linked to a chemotherapy drug, called mafodotin. Belantamab is a form of targeted therapy because it attaches to specific molecules on the surface of cancer cells, known as BCMA receptors, and delivers mafodotin to kill them. Chemotherapy drugs, such as pomalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Anti-inflammatory drugs, such as dexamethasone lower the body's immune response and are used with other drugs in the treatment of some types of cancer. Giving belantamab mafodotin, pomalidomide, and dexamethasone may kill more cancer cells.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, you must not have used an investigational drug or approved systemic anti-myeloma therapy within 14 days before starting the study treatment. It's best to discuss your current medications with the study team to ensure they don't interfere with the trial.

Is the combination of Belantamab Mafodotin, Pomalidomide, and Dexamethasone safe for humans?

Belantamab Mafodotin has been associated with eye-related side effects, such as changes in vision and dry eyes, and is available only through a special program due to these risks. It has been used in patients with multiple myeloma, and while it shows promise, it requires careful monitoring for these side effects. ^{1 2 3 4 5}

What makes the drug combination of Belantamab Mafodotin, Pomalidomide, and Dexamethasone unique for treating multiple myeloma?

This drug combination is unique because it includes Belantamab Mafodotin, an antibody-drug conjugate that targets and kills cancer cells, combined with Pomalidomide and Dexamethasone, which are known to be effective in patients who have relapsed or are resistant to other treatments. This combination offers a novel approach by integrating different mechanisms to potentially improve outcomes for patients with limited treatment options. ^{6 7 8 9 10}

Research Team

Ajay K. Nooka, MD,MPH,FACP

Principal Investigator

Emory University/Winship Cancer Institute

Eligibility Criteria

This trial is for adults over 18 with high-risk myeloma who've had a stem cell transplant within the last year and are not pregnant or breastfeeding. They should have certain genetic markers, good organ function, no severe eye disease, infections, or allergies to study drugs. Participants must agree to use contraception.

Inclusion Criteria

All my side effects from previous cancer treatments are mild, except for hair loss.

I am 18 years old or older.

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

Exclusion Criteria

I am not allergic to belantamab mafodotin or similar drugs.

Participant must not have any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions (including lab abnormalities) that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures

I do not have any infections that need treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive belantamab mafodotin intravenously, pomalidomide orally, and dexamethasone orally in 28-day cycles

Up to 3 years

Monthly visits for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 3 months

Quarterly visits

Treatment Details

Interventions

• Belantamab Mafodotin
• Dexamethasone
• Pomalidomide

Trial Overview The trial tests belantamab mafodotin (a targeted antibody-chemotherapy combo), pomalidomide (a chemotherapy drug), and dexamethasone (an anti-inflammatory) in treating high-risk myeloma patients to see if this combination kills more cancer cells.

Participant Groups

Group I: Treatment (belantamab mafodotin, pomalidomide, dexamethasone) Experimental Treatment 3 Interventions

Patients receive belantamab mafodotin IV over 30 minutes on day 1 of every other cycle, pomalidomide PO QD on days 1-21, and dexamethasone PO QD on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Belantamab Mafodotin is already approved in European Union, United States for the following indications:

Approved in European Union as Blenrep for:

• Relapsed or refractory multiple myeloma

Approved in United States as Blenrep for:

• Relapsed or refractory multiple myeloma

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

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

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In the DREAMM-2 study, after 13 months of follow-up, 32% of patients with relapsed or refractory multiple myeloma achieved an overall response to belantamab mafodotin (belamaf) at a dose of 2.5 mg/kg, indicating its efficacy in a heavily pretreated population.

The study found that belamaf maintained clinical activity without new safety concerns, even in patients experiencing prolonged dose delays due to corneal events, suggesting it is a safe treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longer term outcomes with single-agent belantamab mafodotin in patients with relapsed or refractory multiple myeloma: 13-month follow-up from the pivotal DREAMM-2 study. Lonial, S., Lee, HC., Badros, A., 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 (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 (BLENREP™) is a promising new treatment for relapsed/refractory multiple myeloma, showing at least a partial response in heavily pre-treated patients, indicating its potential efficacy in difficult cases.

The treatment was well tolerated by the patients, suggesting a favorable safety profile, which is important for those who have already undergone multiple therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belantamab Mafodotin and Relapsed/Refractory Multiple Myeloma: This Is Not Game Over. Condorelli, A., Garibaldi, B., Gagliano, C., et al.[2021]

Pomalidomide, when combined with low-dose dexamethasone, significantly improves progression-free survival and overall survival in adults with relapsed and refractory multiple myeloma, based on results from multinational phase II and III studies involving patients who had undergone at least two prior treatments.

The treatment has a manageable safety profile, with the most common serious side effects being neutropenia, infections, anemia, and thrombocytopenia, making it a viable option for patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide: A Review in Relapsed and Refractory Multiple Myeloma. Hoy, SM.[2018]

Pomalidomide, combined with low-dose dexamethasone, has been shown to be effective in treating adult patients with relapsed and refractory multiple myeloma, significantly improving progression-free survival and overall response rates compared to high-dose dexamethasone.

The treatment demonstrated a manageable safety profile and was effective across various patient subgroups, including those who were refractory to previous therapies, indicating its potential as a valuable salvage therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide: a review of its use in patients with recurrent multiple myeloma. Scott, LJ.[2022]

In a study of 108 patients with relapsed and refractory multiple myeloma, pomalidomide (POM) alone or in combination with dexamethasone (POM/DEX) demonstrated a 31% overall response rate and a median time to treatment failure of 4.4 months, indicating substantial efficacy in this challenging patient population.

However, the treatment was associated with significant hematologic toxicities, including neutropenia (55.1%) and thrombocytopenia (33.7%), highlighting the need for new combination therapies that can enhance efficacy while minimizing these adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide with or without dexamethasone for relapsed/refractory multiple myeloma in Japan: a retrospective analysis by the Kansai Myeloma Forum. Matsumura-Kimoto, Y., Kuroda, J., Kaneko, H., et al.[2018]

In a phase 3 trial involving 455 patients with refractory or relapsed multiple myeloma, pomalidomide combined with low-dose dexamethasone significantly improved progression-free survival and overall survival compared to high-dose dexamethasone.

The treatment was effective across all patient subgroups, regardless of their previous treatments, and showed no cross-resistance with prior therapies, making it a strong candidate for standard care in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of prior treatment and depth of response on survival in MM-003, a randomized phase 3 study comparing pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed/refractory multiple myeloma. San Miguel, JF., Weisel, KC., Song, KW., et al.[2022]

Pomalidomide, combined with weekly dexamethasone, shows promising efficacy in patients with multiple myeloma who have not responded to lenalidomide and bortezomib, achieving an overall response rate of 49% at 2 mg and 43% at 4 mg daily.

The treatment demonstrated a 6-month overall survival rate of 78% for the 2 mg cohort and 67% for the 4 mg cohort, with myelosuppression being the most common side effect, indicating that while effective, careful monitoring for toxicity is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide plus low-dose dexamethasone in myeloma refractory to both bortezomib and lenalidomide: comparison of 2 dosing strategies in dual-refractory disease. Lacy, MQ., Allred, JB., Gertz, MA., et al.[2021]

References

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

Longer term outcomes with single-agent belantamab mafodotin in patients with relapsed or refractory multiple myeloma: 13-month follow-up from the pivotal DREAMM-2 study. [2022]

2. 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]

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

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

4. 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]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Belantamab Mafodotin and Relapsed/Refractory Multiple Myeloma: This Is Not Game Over. [2021]

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

Pomalidomide: A Review in Relapsed and Refractory Multiple Myeloma. [2018]

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

Pomalidomide: a review of its use in patients with recurrent multiple myeloma. [2022]

8. Japan pubmed.ncbi.nlm.nih.gov

Pomalidomide with or without dexamethasone for relapsed/refractory multiple myeloma in Japan: a retrospective analysis by the Kansai Myeloma Forum. [2018]

9. Italy pubmed.ncbi.nlm.nih.gov

Impact of prior treatment and depth of response on survival in MM-003, a randomized phase 3 study comparing pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed/refractory multiple myeloma. [2022]

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

Pomalidomide plus low-dose dexamethasone in myeloma refractory to both bortezomib and lenalidomide: comparison of 2 dosing strategies in dual-refractory disease. [2021]