Belantamab Mafodotin + Pd vs Bortezomib + Pd for Multiple Myeloma

(DREAMM 8 Trial)

Recruiting at 169 trial locations

Overseen By EU GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: GlaxoSmithKline

Must be taking: Pomalidomide, Dexamethasone

Must not be taking: Monoclonal antibodies, BCMA therapy

Disqualifiers: Plasma cell leukemia, Cardiovascular risk, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 174 weeks

302 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will evaluate the efficacy and safety of belantamab mafodotin in combination with pomalidomide and dexamethasone (Arm A) compared with that of combination of pomalidomide, bortezomib and dexamethasone (Arm B) in participants with relapsed/refractory multiple myeloma (RRMM).

Will I have to stop taking my current medications?

The trial requires that you stop taking any systemic anti-myeloma therapy, including chemotherapy and systemic steroids, within 14 days before starting the study drug. If you have been treated with a monoclonal antibody drug, you must wait 30 days before starting the study drugs.

Will I have to stop taking my current medications?

The trial requires that you stop any systemic anti-myeloma therapy, including chemotherapy and systemic steroids, at least 14 days before starting the study drug. If you have been treated with a monoclonal antibody drug, you must wait 30 days before starting the study drugs.

What data supports the effectiveness of the drug combination Belantamab Mafodotin + Pd for treating multiple myeloma?

Pomalidomide combined with low-dose dexamethasone has shown effectiveness in patients with relapsed and refractory multiple myeloma, improving progression-free survival and overall response rates. Additionally, bortezomib-based regimens have been effective in improving overall survival in multiple myeloma patients. ^{1 2 3 4 5}

What data supports the effectiveness of the drug combination Belantamab Mafodotin + Pd for treating multiple myeloma?

Research shows that pomalidomide combined with low-dose dexamethasone is effective in patients with multiple myeloma who have not responded to other treatments, improving survival and response rates. Additionally, bortezomib-based regimens have been shown to improve overall survival in multiple myeloma patients. ^{1 2 3 4 5}

What safety data exists for the combination of Belantamab Mafodotin, Bortezomib, and Dexamethasone in treating multiple myeloma?

Bortezomib and dexamethasone have been studied for safety in multiple myeloma, with findings suggesting that adjusting the dose of bortezomib can reduce side effects like gastrointestinal issues. Additionally, a combination of pomalidomide, bortezomib, and dexamethasone has been used safely in patients with relapsed or refractory multiple myeloma, even with dose adjustments for older patients or those with other health conditions. ^{2 6 7 8 9}

Is the combination of Belantamab Mafodotin and Bortezomib with Pomalidomide and Dexamethasone safe for treating multiple myeloma?

Bortezomib combined with dexamethasone has been studied for safety in multiple myeloma, showing that adjusting the dose can reduce side effects like gastrointestinal issues. Pomalidomide, bortezomib, and dexamethasone have been used safely in patients with relapsed or refractory multiple myeloma, with dose adjustments for older patients or those with other health conditions. ^{2 6 7 8 9}

What makes the drug Belantamab Mafodotin unique for treating multiple myeloma?

Belantamab Mafodotin is unique because it is a first-in-class antibody-drug conjugate (a targeted therapy that combines an antibody with a drug) that specifically targets BCMA on myeloma cells, delivering a toxic substance directly to the cancer cells. This approach allows for a more targeted attack on the cancer, potentially leading to deep and durable responses in patients who have already tried multiple other treatments. ^{10 11 12 13 14}

What makes the drug Belantamab Mafodotin unique for treating multiple myeloma?

Belantamab mafodotin is unique because it is a first-in-class antibody-drug conjugate (a type of targeted cancer therapy) that specifically targets BCMA on myeloma cells, delivering a toxic substance directly to the cancer cells. This approach allows it to be effective in patients who have already undergone multiple other treatments. ^{10 11 12 13 14}

Research Team

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Eligibility Criteria

Adults with relapsed/refractory multiple myeloma who've had at least one prior therapy including lenalidomide, and have measurable disease. They must be in relatively good health (ECOG 0-2), possibly post-autologous stem cell transplant, and not have severe ongoing side effects from previous treatments. Excluded are those with certain infections, unstable liver or kidney conditions, recent heart issues or thromboembolism, active bleeding disorders, other cancers unless stable for 2 years, hypersensitivity to trial drugs or their components.

Inclusion Criteria

My organs are functioning well.

I can sign and understand the consent form.

I have had at least one treatment for my multiple myeloma, including a regimen with lenalidomide, and my disease has progressed after the most recent treatment.

Exclusion Criteria

I have an ongoing kidney condition.

I have received treatment targeting BCMA before.

I have not undergone plasmapheresis within the last week.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either belantamab mafodotin in combination with pomalidomide and dexamethasone or pomalidomide, bortezomib, and dexamethasone

Up to approximately 174 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 473 weeks

Treatment Details

Interventions

• Belantamab mafodotin
• Bortezomib
• Dexamethasone
• Pomalidomide

Trial Overview The trial is testing the effectiveness of belantamab mafodotin combined with pomalidomide and dexamethasone against a combination of pomalidomide, bortezomib and dexamethasone in treating multiple myeloma that has come back or didn't respond to treatment.

Participant Groups

Group I: Arm A: Belantamab mafodotin plus Pomalidomide and Dexamethasone Experimental Treatment 3 Interventions

Group II: Arm B: Bortezomib plus Pomalidomide and Dexamethasone Active Control 3 Interventions

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

Findings from Research

Triplet regimens including lenalidomide and dexamethasone show effectiveness for high-risk smoldering multiple myeloma, but more long-term follow-up is necessary to confirm these results.

For newly diagnosed multiple myeloma patients, carfilzomib- and daratumumab-based combinations are promising as safe and effective induction treatments, while maintenance therapy with ixazomib significantly prolongs progression-free survival compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple Myeloma: Clinical Updates From the American Society of Hematology Annual Meeting 2018. Terpos, E., Ntanasis-Stathopoulos, I.[2020]

In patients with newly diagnosed multiple myeloma, the modified regimen of bortezomib, thalidomide, and dexamethasone (VTd-mod) using a lower thalidomide dose (100 mg/day) was found to be noninferior to the traditional higher dose (VTd-label) in terms of overall survival and progression-free survival, while showing better post-transplant response rates.

The combination of daratumumab with the VTd regimen (D-VTd) demonstrated superior efficacy compared to the traditional VTd-label, while maintaining similar safety profiles, supporting its use as a first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety of bortezomib, thalidomide, and dexamethasone (VTd) without and with daratumumab (D-VTd) in CASSIOPEIA versus VTd in PETHEMA/GEM in transplant-eligible patients with newly diagnosed multiple myeloma, using propensity score matching. Moreau, P., Hulin, C., Zweegman, S., et al.[2023]

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]

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]

In a study of 511 patients with newly diagnosed multiple myeloma, the combination of bortezomib, melphalan, and prednisone with thalidomide (VMPT-VT) significantly improved complete response rates and progression-free survival compared to the standard treatment (VMP), with a median progression-free survival of 35.3 months versus 24.8 months.

The 5-year overall survival rate was also higher in the VMPT-VT group (61%) compared to the VMP group (51%), indicating that the addition of thalidomide to the treatment regimen offers a meaningful survival benefit, despite a higher incidence of certain adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: updated follow-up and improved survival. Palumbo, A., Bringhen, S., Larocca, A., et al.[2015]

In a study of 22 patients with relapsed or refractory multiple myeloma, the combination of bortezomib and dexamethasone (BD therapy) resulted in a high response rate, with 77.3% achieving at least a partial response, indicating its efficacy.

Switching to a once-weekly administration of bortezomib after initial twice-weekly treatment significantly reduced severe gastrointestinal side effects while maintaining the therapy's effectiveness, suggesting a safer dosing strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of bortezomib plus dexamethasone therapy for refractory or relapsed multiple myeloma: once-weekly administration of bortezomib may reduce the incidence of gastrointestinal adverse events. Fukushima, T., Nakamura, T., Iwao, H., et al.[2015]

The BLT-D regimen, which combines clarithromycin, low-dose thalidomide, and dexamethasone, showed a high response rate of 93% in 50 patients with multiple myeloma, indicating its efficacy as a treatment option.

While the treatment was generally well-tolerated, neurotoxicity was the main reason for discontinuation, and caution is advised for patients with existing health issues like severe cardiopulmonary disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BLT-D (clarithromycin [Biaxin], low-dose thalidomide, and dexamethasone) for the treatment of myeloma and Waldenström's macroglobulinemia. Coleman, M., Leonard, J., Lyons, L., et al.[2022]

In a study of 85 newly diagnosed multiple myeloma patients, a high-dose bortezomib regimen (1.6 mg/m2) resulted in a significantly higher complete response rate (43.6%) compared to a low-dose regimen (1.3 mg/m2) which had a response rate of only 12.8%.

While the high-dose regimen showed improved efficacy, particularly in younger patients and those with advanced disease, it was associated with a higher incidence of severe diarrhea, leading to more dose reductions in older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase II, open-label and multicenter study of combination regimens of bortezomib at two doses by subcutaneous injection for newly diagnosed multiple myeloma patients. Li, F., Yao, FS., Zhu, XJ., et al.[2021]

In a study of 559 patients with relapsed/refractory multiple myeloma, those treated with the combination of pomalidomide, bortezomib, and dexamethasone (PVd) showed a higher overall response rate (82.8%) and longer median progression-free survival (14.7 months) compared to frail patients receiving only bortezomib and dexamethasone (Vd).

Frail patients receiving PVd experienced a higher frequency of severe treatment-emergent adverse events, but those who had a bortezomib dose adjustment had significantly longer treatment duration (9.3 months) and progression-free survival (12.1 months), suggesting that PVd can improve outcomes even in frail patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide, Bortezomib, and Dexamethasone in Lenalidomide-Pretreated Multiple Myeloma: A Subanalysis of OPTIMISMM by Frailty and Bortezomib Dose Adjustment. Oriol, A., Dimopoulos, M., Schjesvold, F., 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]

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) 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]

The budget impact analysis of belantamab mafodotin (belamaf) for patients with relapsed/refractory multiple myeloma indicates that its introduction would be budget neutral for a US health plan, with minimal cost changes over 3 years.

In a hypothetical health plan with 1 million members, only 33 patients were identified as eligible for treatment, and the analysis showed that the budget impact was most sensitive to treatment duration and drug acquisition costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Budget Impact of Belantamab Mafodotin (Belamaf) Adoption in the Treatment of Patients with Relapsed or Refractory Multiple Myeloma in the United States. Shah, A., Tosh, JC., Ambavane, A., et al.[2022]

References

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

Multiple Myeloma: Clinical Updates From the American Society of Hematology Annual Meeting 2018. [2020]

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

Comparative efficacy and safety of bortezomib, thalidomide, and dexamethasone (VTd) without and with daratumumab (D-VTd) in CASSIOPEIA versus VTd in PETHEMA/GEM in transplant-eligible patients with newly diagnosed multiple myeloma, using propensity score matching. [2023]

3. 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]

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

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

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

Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: updated follow-up and improved survival. [2015]

6. Greece pubmed.ncbi.nlm.nih.gov

Efficacy and safety of bortezomib plus dexamethasone therapy for refractory or relapsed multiple myeloma: once-weekly administration of bortezomib may reduce the incidence of gastrointestinal adverse events. [2015]

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

BLT-D (clarithromycin [Biaxin], low-dose thalidomide, and dexamethasone) for the treatment of myeloma and Waldenström's macroglobulinemia. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

A randomized phase II, open-label and multicenter study of combination regimens of bortezomib at two doses by subcutaneous injection for newly diagnosed multiple myeloma patients. [2021]

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

Pomalidomide, Bortezomib, and Dexamethasone in Lenalidomide-Pretreated Multiple Myeloma: A Subanalysis of OPTIMISMM by Frailty and Bortezomib Dose Adjustment. [2023]

10. 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]

11. 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]

12. 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]

13. England pubmed.ncbi.nlm.nih.gov

Belantamab mafodotin in combination with novel agents in relapsed/refractory multiple myeloma: DREAMM-5 study design. [2021]

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

Budget Impact of Belantamab Mafodotin (Belamaf) Adoption in the Treatment of Patients with Relapsed or Refractory Multiple Myeloma in the United States. [2022]