Evaluation of Efficacy and Safety of Belantamab Mafodotin, Bortezomib and Dexamethasone Versus Daratumumab, Bortezomib and Dexamethasone in Participants With Relapsed/Refractory Multiple Myeloma

Study Overview
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Brief Summary
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This is a Phase 3, randomized, open-label study designed to evaluate safety and efficacy of belantamab mafodotin in combination with bortezomib/dexamethasone (Arm A) versus daratumumab in combination with bortezomib/dexamethasone (Arm B) in the participants with relapsed recurrent multiple myeloma.

Official Title
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DREAMM 7: A Multicenter, Open-Label, Randomized Phase III Study to Evaluate the Efficacy and Safety of the Combination of Belantamab Mafodotin, Bortezomib, and Dexamethasone (B-Vd) Compared With the Combination of Daratumumab, Bortezomib and Dexamethasone (D-Vd) in Participants With Relapsed/Refractory Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Belantamab mafodotin
* Drug: Daratumumab
* Drug: Bortezomib
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of multiple myeloma as defined by the International Myeloma Working Group (IMWG) criteria. Previously treated with at least 1 prior line of multiple myeloma (MM) therapy, and must have documented disease progression during or after their most recent therapy. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. Must have at least 1 aspect of measurable disease, defined as one of the following; Urine M-protein excretion >=200 mg per 24-hour, or Serum M-protein concentration >=0.5 grams per deciliter (g/dL), or Serum free light chain (FLC) assay: involved FLC level >=10 mg per dL (>=100 mg per liter) and an abnormal serum free light chain ratio (<0.26 or >1.65). All prior treatment-related toxicities (defined by National Cancer Institute Common Toxicity Criteria for Adverse Events [NCI-CTCAE] version 5.0) must be <=Grade 1 at the time of enrollment, except for alopecia. Adequate organ function Exclusion Criteria: Intolerant to daratumumab. Refractory to daratumumab or any other anti-CD38 therapy (defined as progressive disease during treatment with anti-CD38 therapy, or within 60 days of completing that treatment). Intolerant to bortezomib, or refractory to bortezomib (defined as progressive disease during treatment with a bortezomib-containing regimen of 1.3 mg/m^2 twice weekly, or within 60 days of completing that treatment). Note: participants with progressive disease during treatment with a weekly bortezomib regimen are allowed. Ongoing Grade 2 or higher peripheral neuropathy or neuropathic pain. Prior treatment with anti-B-cell maturation antigen (anti-BCMA) therapy. Prior allogenic stem cell transplant. Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions, including renal, liver, cardiovascular, or certain prior malignancies. Corneal epithelial disease.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Belantamab mafodotin and Bortezomib plus Dexamethasone (Arm A)<br> | Drug: Belantamab mafodotin<br>* Humanized anti-B-cell maturation antigen (BCMA) antibody/drug conjugate<br>Drug: Bortezomib<br>* Proteasome Inhibitor<br>Drug: Dexamethasone<br>* Synthetic glucocorticoid with anti-tumor activity<br>|
| Active Comparator: Daratumumab and Bortezomib plus Dexamethasone (Arm B)<br> | Drug: Daratumumab<br>* Anti-cluster of differentiation 38 [CD-38] monoclonal antibody<br>Drug: Bortezomib<br>* Proteasome Inhibitor<br>Drug: Dexamethasone<br>* Synthetic glucocorticoid with anti-tumor activity<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Time from the date of randomization until the earliest date of to the first documented disease progression or death due to any cause, whichever occurs first | Up to an average of 37 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate (CRR) | Percentage of participants with a confirmed complete response or better. | Up to 74 months | 
| Overall response rate (ORR) | Percentage of participants with a confirmed partial response or better. | Up to 74 months | 
| Clinical Benefit Rate (CBR) | Percentage of participants with a confirmed partial response or better | Up to 74 months | 
| Duration of response (DoR) | Time from first documented evidence of partial response or better to date of first documented progression or death, whichever occurs first. | Up to 74 months | 
| Time to response (TTR) | Time from the date of randomization and the first documented evidence of response among participants who achieve partial response or better. | Up to 74 months | 
| Time to Progression (TTP) | Time from the date of randomization until the first documented date of disease progression or death, whichever occurs first. | Up to 74 months | 
| Overall survival (OS) | Time from the date of randomization until the date of death due to any cause. | Up to 74 months | 
| Progression-free survival on subsequent line of therapy (PFS2) | Time from start of study treatment to disease progression after initiation of new anti-myeloma therapy or death from any cause, whichever occurs first. If disease progression after new antimyeloma therapy cannot be measured, a PFS event is defined as the date of discontinuation of new anti-myeloma therapy, or death from any cause, whichever is earlier . | Up to 74 months | 
| Minimal Residual Disease (MRD) negativity rate | Minimal Residual Disease (MRD) negativity rate, defined as the percentage of participants who are MRD negative by next generation sequencing (NGS) | Up to 74 months | 
| Number of participants with adverse events (AEs) | AEs will be collected, including abnormal laboratory parameters. | Up to 74 months | 
| Number of Participants with Clinically Significant Changes in Clinical Laboratory Parameters |  | Up to 74 months | 
| Number of participants with abnormal ocular findings on ophthalmic examination | Ophthalmic examination will assess abnormal findings. | Up to 74 months | 
| Plasma concentrations of belantamab mafodotin at indicated time points | Plasma concentrations of belantamab mafodotin in Arm A. | Up to 74 months | 
| Plasma concentrations of monomethyl auristatin-F with a cysteine linker (cys-mcMMAF) at indicated time points | Plasma concentrations of cys-mcMMAF in Arm A. | Up to 74 months | 
| Number of participants with positive anti-drug antibodies (ADAs) against belantamab mafodotin | Plasma concentrations of belantamab mafodotin ADAs in Arm A. | Up to 74 months | 
| Titers of ADAs against belantamab mafodotin | Titers of ADAs in Arm A. | Up to 74 months | 
| Number of Participants with Maximum post-baseline change from baseline in individual items of Patient-Reported Outcome Version of the Common Term Criteria for Adverse Events (PRO-CTCAE) | PRO-CTCAE questionnaire assesses side effect symptoms in cancer clinical trials using a PRO-CTCAE score.. | Up to 74 months | 
| Change from Baseline in health related quality of life (HRQoL) as measured by European Organization for Research and Treatment of Cancer Quality of life Questionnaire 30-item core module (EORTC QLQ-C30) | EORTC Quality of Life questionnaire QLQ-C30 on a scale of 0-100. Lower scores correlate with worse quality of life and higher scores correlate with better quality of life. | Baseline and Up to 74 months | 
| Change from Baseline in HRQoL as measured by EORTC IL52, 20-Item Multiple Myeloma Module (QLQ-MY20) | EORTC IL52 Quality of Life questionnaire QLQ-C30 on a scale of 0-100. Lower scores correlate with worse quality of life and higher scores correlate with better quality of life. | Baseline and Up to 74 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Daratumumab, Belantamab mafodotin, Relapsed/refractory multiple myeloma, Bortezomib, Dexamethasone, Multiple Myeloma