Evaluation of Efficacy and Safety of Belantamab Mafodotin, Bortezomib and Dexamethasone Versus Daratumumab, Bortezomib and Dexamethasone in Participants With Relapsed/Refractory Multiple Myeloma (DREAMM 7)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Belantamab mafodotin; Drug: Bortezomib; Drug: Dexamethasone; Drug: Daratumumab

Detailed Description

Approximately 478 participants will be randomized 1:1 to Arm A (B-Vd) or Arm B (D-Vd). Treatment will continue in both arms until progressive disease, death, unacceptable toxicity, withdrawal of consent or end of study, whichever occurs first.

• Study Type: Interventional
• Enrollment (Actual): 571
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • GSK Investigational Site
    • Liverpool, New South Wales, Australia, 2170
      • GSK Investigational Site
    • St Leonards, New South Wales, Australia, 2065
      • GSK Investigational Site
    • Waratah, New South Wales, Australia, 2298
      • GSK Investigational Site
    • Wollongong, New South Wales, Australia, 2500
      • GSK Investigational Site
  • Queensland
    • Benowa, Queensland, Australia, 4217
      • GSK Investigational Site
    • Herston, Queensland, Australia, 4029
      • GSK Investigational Site
  • South Australia
    • Kurralta Park, South Australia, Australia, 5037
      • GSK Investigational Site
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • GSK Investigational Site
    • Heidelberg, Victoria, Australia, 3084
      • GSK Investigational Site
    • Melbourne, Victoria, Australia, 3004
      • GSK Investigational Site
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • GSK Investigational Site
    • Nedlands, Western Australia, Australia, 6009
      • GSK Investigational Site
• Belgium
  • Brussel, Belgium, 1090
    • GSK Investigational Site
  • Bruxelles, Belgium, 1200
    • GSK Investigational Site
  • Gent, Belgium, 9000
    • GSK Investigational Site
  • Roeselare, Belgium, 8800
    • GSK Investigational Site
• Brazil
  • Rio de Janeiro, Brazil, 22775001
    • GSK Investigational Site
  • São Paulo, Brazil, 04537-080
    • GSK Investigational Site
  • São Paulo, Brazil, 05403-000
    • GSK Investigational Site
  • Rio Grande Do Norte
    • Natal, Rio Grande Do Norte, Brazil, 59075-740
      • GSK Investigational Site
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
      • GSK Investigational Site
  • Santa Catarina
    • Florianopolis, Santa Catarina, Brazil, 88020-210
      • GSK Investigational Site
    • Joinville, Santa Catarina, Brazil, 89201-260
      • GSK Investigational Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • GSK Investigational Site
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • GSK Investigational Site
    • Québec, Ontario, Canada, G1J 1Z4
      • GSK Investigational Site
    • Toronto, Ontario, Canada, M4N 3M5
      • GSK Investigational Site
  • Quebec
    • Montréal, Quebec, Canada, H4J 1C5
      • GSK Investigational Site
• China
  • Beijing, China, 100044
    • GSK Investigational Site
  • Beijing, China, 100191
    • GSK Investigational Site
  • Beijing, China, 100020
    • GSK Investigational Site
  • GuangZhou, China, 510515
    • GSK Investigational Site
  • Jiang Su Province, China, 215006
    • GSK Investigational Site
  • Shenyang, China, 110001
    • GSK Investigational Site
  • Tianjin, China, 300020
    • GSK Investigational Site
  • Tianjin, China, 300052
    • GSK Investigational Site
  • Wuhan, China, 430022
    • GSK Investigational Site
  • Zhengzhou, China, 450052
    • GSK Investigational Site
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • GSK Investigational Site
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • GSK Investigational Site
  • Jilin
    • Changchun, Jilin, China, 130012
      • GSK Investigational Site
  • Shandong
    • Jianan, Shandong, China, 250012
      • GSK Investigational Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • GSK Investigational Site
• Czechia
  • Brno, Czechia, 625 00
    • GSK Investigational Site
  • Hradec Kralove, Czechia, 500 05
    • GSK Investigational Site
  • Ostrava, Czechia, 708 52
    • GSK Investigational Site
  • Praha 2, Czechia, 128 08
    • GSK Investigational Site
• France
  • Amiens cedex 1, France, 80054
    • GSK Investigational Site
  • Caen cedex 9, France, 14033
    • GSK Investigational Site
  • Nice, France, 06200
    • GSK Investigational Site
  • Paris cedex 13, France, 75651
    • GSK Investigational Site
  • Rennes cedex 9, France, 35033
    • GSK Investigational Site
• Germany
  • Baden-Wuerttemberg
    • Ulm, Baden-Wuerttemberg, Germany, 89081
      • GSK Investigational Site
  • Bayern
    • Muenchen, Bayern, Germany, 81377
      • GSK Investigational Site
    • Wuerzburg, Bayern, Germany, 97080
      • GSK Investigational Site
  • Nordrhein-Westfalen
    • Duesseldorf, Nordrhein-Westfalen, Germany, 40225
      • GSK Investigational Site
    • Koeln, Nordrhein-Westfalen, Germany, 50937
      • GSK Investigational Site
  • Thueringen
    • Jena, Thueringen, Germany, 07747
      • GSK Investigational Site
• Greece
  • Alexandroupolis, Greece, 68 100
    • GSK Investigational Site
  • Athens, Greece, 11528
    • GSK Investigational Site
  • Thessaloniki, Greece, 54007
    • GSK Investigational Site
• Israel
  • Jerusalem, Israel, 91120
    • GSK Investigational Site
  • Kfar Saba, Israel, 44281
    • GSK Investigational Site
  • Tel Aviv, Israel, 64239
    • GSK Investigational Site
  • Tel Hashomer, Israel, 52621
    • GSK Investigational Site
• Italy
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • GSK Investigational Site
    • Meldola, Emilia-Romagna, Italy, 47014
      • GSK Investigational Site
    • Ravenna, Emilia-Romagna, Italy, 48123
      • GSK Investigational Site
  • Lazio
    • Roma, Lazio, Italy, 00168
      • GSK Investigational Site
  • Lombardia
    • Bergamo, Lombardia, Italy, 24127
      • GSK Investigational Site
    • Brescia, Lombardia, Italy, 25123
      • GSK Investigational Site
    • Milano, Lombardia, Italy, 20133
      • GSK Investigational Site
  • Piemonte
    • Torino, Piemonte, Italy, 10126
      • GSK Investigational Site
  • Sicilia
    • Catania, Sicilia, Italy, 95123
      • GSK Investigational Site
  • Toscana
    • Siena, Toscana, Italy, 53100
      • GSK Investigational Site
• Japan
  • Aichi, Japan, 467-8602
    • GSK Investigational Site
  • Aichi, Japan, 441-8570
    • GSK Investigational Site
  • Aichi, Japan, 446-8602
    • GSK Investigational Site
  • Aomori, Japan, 030-8553
    • GSK Investigational Site
  • Chiba, Japan, 296-8602
    • GSK Investigational Site
  • Ehime, Japan, 790-8524
    • GSK Investigational Site
  • Fukuoka, Japan, 806-8501
    • GSK Investigational Site
  • Fukuoka, Japan, 807-8555
    • GSK Investigational Site
  • Fukuoka, Japan, 810-8563
    • GSK Investigational Site
  • Fukuoka, Japan, 815-8555
    • GSK Investigational Site
  • Fukushima, Japan, 960-1295
    • GSK Investigational Site
  • Gifu, Japan, 503-8502
    • GSK Investigational Site
  • Gunma, Japan, 377-0280
    • GSK Investigational Site
  • Hokkaido, Japan, 060-8648
    • GSK Investigational Site
  • Hyogo, Japan, 670-8540
    • GSK Investigational Site
  • Kanagawa, Japan, 247-8533
    • GSK Investigational Site
  • Kanagawa, Japan, 221-0855
    • GSK Investigational Site
  • Kochi, Japan, 781-8555
    • GSK Investigational Site
  • Kyoto, Japan, 602-8566
    • GSK Investigational Site
  • Nagano, Japan, 392-8510
    • GSK Investigational Site
  • Okayama, Japan, 701-1192
    • GSK Investigational Site
  • Osaka, Japan, 545-8586
    • GSK Investigational Site
  • Osaka, Japan, 530-0012
    • GSK Investigational Site
  • Shizuoka, Japan, 411-8777
    • GSK Investigational Site
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • GSK Investigational Site
  • Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 06351
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 06591
    • GSK Investigational Site
  • Ulsan, Korea, Republic of, 44033
    • GSK Investigational Site
• Netherlands
  • Dordrecht, Netherlands, 3318 AT
    • GSK Investigational Site
  • Groningen, Netherlands, 9713 GZ
    • GSK Investigational Site
• New Zealand
  • Christchurch, New Zealand, 8011
    • GSK Investigational Site
  • Dunedin, New Zealand, 9054
    • GSK Investigational Site
  • Newtown, New Zealand, 6021
    • GSK Investigational Site
  • Takapuna, Auckland, New Zealand, 1309
    • GSK Investigational Site
• Poland
  • Chorzow, Poland, 41-500
    • GSK Investigational Site
  • Krakow, Poland, 30510
    • GSK Investigational Site
  • Lodz, Poland, 93-513
    • GSK Investigational Site
  • Lublin, Poland, 20-081
    • GSK Investigational Site
  • Lublin, Poland, 20-090
    • GSK Investigational Site
  • Nowy Sacz, Poland, 33-300
    • GSK Investigational Site
  • Poznan, Poland, 60-569
    • GSK Investigational Site
  • Warszawa, Poland, 02-781
    • GSK Investigational Site
• Russian Federation
  • Moscow, Russian Federation, 125284
    • GSK Investigational Site
  • Nizhniy Novgorod, Russian Federation, 603126
    • GSK Investigational Site
  • Novosibirsk, Russian Federation, 630087
    • GSK Investigational Site
  • Samara, Russian Federation, 443021
    • GSK Investigational Site
  • Saratov, Russian Federation, 410028
    • GSK Investigational Site
  • St'Petersburg, Russian Federation, 191024
    • GSK Investigational Site
  • St. Petersburg, Russian Federation, 197 089
    • GSK Investigational Site
  • Ufa, Russian Federation, 450083
    • GSK Investigational Site
• Spain
  • Badalona, Spain, 08916
    • GSK Investigational Site
  • Barcelona, Spain, 08035
    • GSK Investigational Site
  • Barcelona, Spain, 08908
    • GSK Investigational Site
  • Cáceres, Spain, 10003
    • GSK Investigational Site
  • Gijón, Spain, 33394
    • GSK Investigational Site
  • Madrid, Spain, 28007
    • GSK Investigational Site
  • Murcia, Spain, 30008
    • GSK Investigational Site
  • Móstoles, Spain, 28933
    • GSK Investigational Site
  • Pamplona, Spain, 31008
    • GSK Investigational Site
  • Pozuelo De Alarcón/Madrid, Spain, 28223
    • GSK Investigational Site
  • Salamanca, Spain, 37007
    • GSK Investigational Site
• United Kingdom
  • Bournemouth, United Kingdom, BH7 7DW
    • GSK Investigational Site
  • Cardiff, United Kingdom, CF14 4XW
    • GSK Investigational Site
  • Dundee, United Kingdom, DD1 9SY
    • GSK Investigational Site
  • Leicester, United Kingdom, LE1 5WW
    • GSK Investigational Site
  • London, United Kingdom, W12 0NN
    • GSK Investigational Site
  • Staffordshire
    • Stoke-on-Trent, Staffordshire, United Kingdom, ST4 6QG
      • GSK Investigational Site
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • GSK Investigational Site
• United States
  • Arizona
    • Yuma, Arizona, United States, 85364
      • GSK Investigational Site
  • Colorado
    • Denver, Colorado, United States, 80218
      • GSK Investigational Site
  • Kansas
    • Westwood, Kansas, United States, 66205
      • GSK Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • GSK Investigational Site
  • Texas
    • Tyler, Texas, United States, 75702
      • GSK Investigational Site
  • Virginia
    • Roanoke, Virginia, United States, 24014
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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;

  1. Urine M-protein excretion >=200 mg per 24-hour, or
  2. Serum M-protein concentration >=0.5 grams per deciliter (g/dL), or
  3. 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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
Number of participants with adverse events (AEs)	AEs will be collected, including abnormal 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
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
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
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
Number of Participants with Clinically Significant Changes in Clinical Laboratory Parameters		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 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
Overall survival (OS)	Time from the date of randomization until the date of death due to any cause.	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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2020
• Primary Completion (Actual): October 2, 2023
• Study Completion (Estimated): June 19, 2026

Study Registration Dates

• First Submitted: January 27, 2020
• First Submitted That Met QC Criteria: January 27, 2020
• First Posted (Actual): January 29, 2020

Study Record Updates

• Last Update Posted (Estimated): December 13, 2023
• Last Update Submitted That Met QC Criteria: December 7, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Multiple Myeloma; Daratumumab; Dexamethasone; Bortezomib; Belantamab mafodotin; Relapsed/refractory multiple myeloma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone; Daratumumab; Bortezomib
• Other Study ID Numbers: 207503; 2018-003993-29 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No