Study of Single Agent Belantamab Mafodotin Versus Pomalidomide Plus Low-dose Dexamethasone (Pom/Dex) in Participants With Relapsed/Refractory Multiple Myeloma (RRMM)

NCT ID: NCT04162210

Last Updated: 2025-06-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 325 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-02
• Study Completion Date: 2026-07-01

Brief Summary

This open-label, randomized study for evaluating the efficacy and safety of single agent belantamab mafodotin when compared to pom/dex in participants with RRMM. Participants will be randomized in a 2:1 ratio to receive either single agent belantamab mafodotin or pom/dex. Belantamab mafodotin will be administered on Day 1 (D1) at every 3 weeks (Q3W) schedule. Pomalidomide will be administered daily on Days 1 to 21 of each 28-day cycle, with dexamethasone administered once weekly (Days 1, 8, 15, and 22). Participants in both arms will be treated until disease progression, death, unacceptable toxicity, withdrawal of consent, and lost to follow-up or end of study, whichever comes first.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Participants receiving Belantamab mafodotin

Participants will receive belantamab mafodotin single agent dose on Day 1 of Q3W

Group Type: EXPERIMENTAL

Belantamab mafodotin

Intervention Type: DRUG

Belantamab mafodotin will be administered.

Participants receiving pom/dex

Participants will receive pomalidomide daily on Days 1 to 21 of each 28-day cycle, with dexamethasone once weekly on Days 1, 8, 15 and 22.

Group Type: ACTIVE_COMPARATOR

Pom/dex (Pomalidomide plus low dose Dexamethasone)

Intervention Type: DRUG

Pomalidomide and Dexamethasone will be administered.

Interventions

Belantamab mafodotin

Belantamab mafodotin will be administered.

Intervention Type: DRUG

Pom/dex (Pomalidomide plus low dose Dexamethasone)

Pomalidomide and Dexamethasone will be administered.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Capable of giving signed informed consent.
• Participants must be 18 or older, at the time of signing the informed consent. In Republic of Korea, participants must be over 19 years of age inclusive, at the time of signing informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Histologically or cytologically confirmed diagnosis of Multiple myeloma (MM) as defined according to IMWG, and : Has undergone autologous stem cell transplant (SCT), or is considered transplant ineligible; Has received at least 2 prior lines of anti-myeloma treatments, including at least 2 consecutive cycles of both lenalidomide and a proteasome inhibitor (given separately or in combination), and must have documented disease progression on, or within 60 days of, completion of the last treatment or must be non-responsive while on last treatment, where non-responsive is defined as not achieving at least Minimal Response (MR) after 2 complete treatment cycles. In such cases lack of achieving of at least MR must be determined no earlier than at least 4 weeks after the last treatment.
• Has measurable disease with at least one of the following: Serum M-protein >=0.5 gram per deciliter (g/dL) (>=5 gram per Liter); Urine M-protein >=200 mg/24 hours; Serum free light chain (FLC) assay: Involved FLC level >=10 milligram per deciliter (mg/dL) (>=100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65).
• Participants with a history of autologous SCT are eligible for study participation provided the following eligibility criteria are met: Transplant was >100 days prior to initiating study treatment; No active infection(s).
• Adequate organ system functions as defined: Absolute neutrophil count (ANC) >=1.0*10^9/L; Hemoglobin >= 8.0 g/dL; Platelets >= 50x10^9/L; Total bilirubin <=1.5* Upper limit of normal (ULN) (isolated bilirubin >1.5*ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent); ALT <=2.5*ULN; Estimated glomerular filtration rate (eGFR) >=30 milliliter per minute per 1.73 square meter (mL/min/1.73 m^2); Spot urine (albumin/creatinine ratios) <=500 milligram per gram (mg/g) (56 milligram per millimoles [mg/mmol]).
• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Male participants are eligible to participate if they agree to the following during the intervention period and until 6 months after the last dose of study intervention to allow for clearance of any altered sperm: Refrain from donating sperm PLUS, either: Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR Must agree to use contraception/barrier as detailed below depending on whether they are randomised to Arm 1 (belantamab mafodotin) or Arm 2 (pom/dex), even if they have undergone a successful vasectomy: Agree to use a male condom throughout study treatment including the 6 month follow-up period even if they have undergone a successful vasectomy and a female partner to use an additional highly effective contraceptive method with a failure rate of <1 percent per year when having sexual intercourse with a pregnant woman or a woman of childbearing potential who is not currently pregnant. Four weeks for male participants on Treatment Arm 2 (pom/dex).
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP) OR Is a WOCBP and agrees to abide by the following: Arm 1 (belantamab mafodotin): Use a contraceptive method that is highly effective (with a failure rate of <1 percent per year) which includes abstinence, preferably with low user dependency during the intervention period and for 4 months after the last dose of study treatment. Arm 2 (pom/dex): Due to pomalidomide being a thalidomide analogue with risk for embryofetal toxicity and prescribed under a pregnancy prevention/controlled distribution program, WOCBP participants will be eligible if they commit either to abstain continuously from heterosexual sexual intercourse or to use two methods of reliable birth control (one method that is highly effective), beginning 4 weeks prior to initiating treatment with pomalidomide, during therapy, during dose interruptions and continuing for at least 4 weeks following discontinuation of pomalidomide treatment. Two negative pregnancy tests must be obtained prior to initiating therapy. The first test should be performed within 10-14 days and the second test within 24 hours prior to prescribing pomalidomide therapy. And agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should confirm the effectiveness of the contraceptive method(s) ahead of the first dose of study intervention.
• All prior treatment-related toxicities (defined by National Cancer Institute- Common Toxicity Criteria for Adverse Events [NCI-CTCAE], version 5.0, 2017) must be <=Grade 1 at the time of enrollment, except for alopecia and Grade 2 peripheral neuropathy.

• 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 with study procedures.
• History of (non-infectious) pneumonitis that required steroids, or current pneumonitis.
• Evidence of active mucosal or internal bleeding.
• Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. (Stable chronic liver disease [including Gilbert's syndrome or asymptomatic gallstones] or hepatobiliary involvement of malignancy is acceptable if participant otherwise meets entry criteria)
• Participants with previous or concurrent malignancies other than multiple myeloma are excluded, unless the second malignancy has been considered medically stable for at least 2 years. The participant must not be receiving active therapy, other than hormonal therapy for this disease. (Participants with curatively treated non-melanoma skin cancer are allowed without a 2-year restriction).
• Evidence of cardiovascular risk including any of the following: Evidence of current clinically significant uncontrolled arrhythmias including clinically significant electrocardiogram (ECG) abnormalities including 2nd degree (Mobitz Type II) or 3rd degree atrioventricular block; History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 3 months of Screening; Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system; Uncontrolled hypertension.
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to belantamab mafodotin, pomalidomide, dexamethasone or any of the components of the study intervention.
• Pregnant or lactating female.
• Active infection requiring treatment.
• Known human immunodeficiency virus (HIV), unless the participant can meet all of the following criteria: Established anti-retroviral therapy (ART) for at least 4 weeks and HIV viral load <400 copies/mL; CD4+ T-cell (CD4+) counts ≥350 cells/uL; No history of AIDS-defining opportunistic infections within the last 12 months.(Consideration must be given to ART and prophylactic antimicrobials that may have a drug-drug interaction and/or overlapping toxicities with belantamab mafodotin or other combination products as relevant)
• Participants with Hepatitis B will be excluded unless the following criteria can be met: If the participant is hepatitis B core antibody (HbcAb) positive or hepatitis B surface antigen (HbsAg) negative, then hepatitis B virus (HBV) deoxyribonucleic acid (DNA) should be undectectable at the time of screening; If HbsAg+ at screening or <=3 months prior to first dose of study treatment, then HBV DNA should be undetectable, highly effective antiviral treatment should be started ≥4 weeks prior to first dose of study treatment, exclusion of participants with cirrhosis and participants in Japan must test hepatitis B e antigen (HBeAg) and hepatitis B e antibody (HBeAb ).
• Positive hepatitis C antibody test result or positive hepatitis C Ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment unless the participant can meet the following criteria: Hepatitis C RNA test negative at Screening and successful anti-viral treatment (usually 8 weeks duration) is required, followed by a negative HCV RNA test after a washout period of at least 4 weeks (Hepatitis RNA is optional and participants with negative Hepatitis C antibody test are not required to also undergo Hepatitis C RNA testing).
• Participants unable to tolerate thromboembolic prophylaxis.
• Current corneal epithelial disease except for mild punctate keratopathy.

Exclusion Criteria

• Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes); active plasma cell leukemia at the time of screening.
• Systemic anti-myeloma therapy or use of an investigational drug within <14 days or 5 half-lives, whichever is shorter, before the first dose of study intervention.
• Prior treatment with an anti-MM monoclonal antibody within 30 days prior to receiving the first dose of study intervention.
• Prior B cell maturation antigen (BCMA)-targeted therapy or prior pomalidomide treatment.
• Plasmapheresis within 7 days prior to the first dose of study intervention.
• Prior allogeneic stem cell transplant. (Participants who have undergone syngeneic transplant will be allowed only if no history of, or currently active, Graft-Versus-Host Disease [GvHD]).
• Any major surgery within the last 4 weeks.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Tucson, Arizona, United States

GSK Investigational Site

Pueblo, Colorado, United States

GSK Investigational Site

Detroit, Michigan, United States

GSK Investigational Site

Albany, New York, United States

GSK Investigational Site

Clifton Park, New York, United States

GSK Investigational Site

Cincinnati, Ohio, United States

GSK Investigational Site

Corvallis, Oregon, United States

GSK Investigational Site

Eugene, Oregon, United States

GSK Investigational Site

Tyler, Texas, United States

GSK Investigational Site

Milwaukee, Wisconsin, United States

GSK Investigational Site

Gosford NSW, New South Wales, Australia

GSK Investigational Site

Liverpool, New South Wales, Australia

GSK Investigational Site

St Leonards, New South Wales, Australia

GSK Investigational Site

Woodville, South Australia, Australia

GSK Investigational Site

Hobart, Tasmania, Australia

GSK Investigational Site

Clayton, Victoria, Australia

GSK Investigational Site

Fitzroy, Victoria, Australia

GSK Investigational Site

Geelong, Victoria, Australia

GSK Investigational Site

Nedlands, Western Australia, Australia

GSK Investigational Site

St Albans, , Australia

GSK Investigational Site

Bruges, , Belgium

GSK Investigational Site

Brussels, , Belgium

GSK Investigational Site

Brussels, , Belgium

GSK Investigational Site

Edegem, , Belgium

GSK Investigational Site

Kortrijk, , Belgium

GSK Investigational Site

Yvoir, , Belgium

GSK Investigational Site

Porto Alegre, Rio Grande do Sul, Brazil

GSK Investigational Site

Curitiba, , Brazil

GSK Investigational Site

Fortaleza, , Brazil

GSK Investigational Site

Porto Alegre, , Brazil

GSK Investigational Site

Rio de Janeiro, , Brazil

GSK Investigational Site

São Paulo, , Brazil

GSK Investigational Site

São Paulo, , Brazil

GSK Investigational Site

São Paulo, , Brazil

GSK Investigational Site

São Paulo, , Brazil

GSK Investigational Site

Pleven, , Bulgaria

GSK Investigational Site

Plovdiv, , Bulgaria

GSK Investigational Site

Sofia, , Bulgaria

GSK Investigational Site

Sofia, , Bulgaria

GSK Investigational Site

Sofia, , Bulgaria

GSK Investigational Site

Sofia, , Bulgaria

GSK Investigational Site

Edmonton, Alberta, Canada

GSK Investigational Site

Beijing, , China

GSK Investigational Site

Beijing, , China

GSK Investigational Site

Beijing, , China

GSK Investigational Site

Beijing, , China

GSK Investigational Site

Changsha, , China

GSK Investigational Site

Chengdu, , China

GSK Investigational Site

Guangzhou, , China

GSK Investigational Site

Hangzhou, , China

GSK Investigational Site

Nanchang, , China

GSK Investigational Site

Shenzhen, , China

GSK Investigational Site

Tianjin, , China

GSK Investigational Site

Tianjin, , China

GSK Investigational Site

Xuzhou, , China

GSK Investigational Site

Zhengzhou, , China

GSK Investigational Site

Le Mans, , France

GSK Investigational Site

Montpellier, , France

GSK Investigational Site

Poitiers, , France

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Tübingen, , Germany

GSK Investigational Site

Athens, , Greece

GSK Investigational Site

Athens, , Greece

GSK Investigational Site

Haidari - Athens, , Greece

GSK Investigational Site

Larissa, , Greece

GSK Investigational Site

Pátrai, , Greece

GSK Investigational Site

Thessaloniki, , Greece

GSK Investigational Site

Thessaloniki, , Greece

GSK Investigational Site

Budapest, , Hungary

GSK Investigational Site

Budapest, , Hungary

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Budapest, , Hungary

GSK Investigational Site

Debrecen, , Hungary

GSK Investigational Site

Kaposvár, , Hungary

GSK Investigational Site

Nyíregyháza, , Hungary

GSK Investigational Site

Bologna, , Italy

GSK Investigational Site

Brescia, , Italy

GSK Investigational Site

Catanzaro, , Italy

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Milan, , Italy

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Milan, , Italy

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Pavia, , Italy

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Perugia, , Italy

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Ravenna, , Italy

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Roma, , Italy

GSK Investigational Site

San Giovanni Rotondo FG, , Italy

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Siena, , Italy

GSK Investigational Site

Aichi, , Japan

GSK Investigational Site

Chiba, , Japan

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Ehime, , Japan

GSK Investigational Site

Fukushima, , Japan

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Gifu, , Japan

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Gunma, , Japan

GSK Investigational Site

Hokkaido, , Japan

GSK Investigational Site

Kyoto, , Japan

GSK Investigational Site

Kyoto, , Japan

GSK Investigational Site

Osaka, , Japan

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Tokyo, , Japan

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Tokyo, , Japan

GSK Investigational Site

Amersfoort, , Netherlands

GSK Investigational Site

Gdansk, , Poland

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Krakow, , Poland

GSK Investigational Site

Torun, , Poland

GSK Investigational Site

Kaluga, , Russia

GSK Investigational Site

Kirov, , Russia

GSK Investigational Site

Krasnoyarsk, , Russia

GSK Investigational Site

Nizhny Novgorod, , Russia

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Novosibirsk, , Russia

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Saint Petersburg, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Samara, , Russia

GSK Investigational Site

Sochi, , Russia

GSK Investigational Site

Syktyvkar, , Russia

GSK Investigational Site

Tula, , Russia

GSK Investigational Site

Yekaterinburg, , Russia

GSK Investigational Site

Gyeonggi-do, , South Korea

GSK Investigational Site

Hwasun, , South Korea

GSK Investigational Site

Incheon, , South Korea

GSK Investigational Site

Seongnam-si Gyeonggi-do, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

L'Hospitalet de Llobrega, , Spain

GSK Investigational Site

Málaga, , Spain

GSK Investigational Site

PamplonaNavarra, , Spain

GSK Investigational Site

Pozuelo de AlarcOn Madr, , Spain

GSK Investigational Site

Santiago de Compostela, , Spain

GSK Investigational Site

Airdrie, , United Kingdom

GSK Investigational Site

Dundee, , United Kingdom

GSK Investigational Site

Edinburgh, , United Kingdom

GSK Investigational Site

London, , United Kingdom

GSK Investigational Site

London, , United Kingdom

GSK Investigational Site

Nottingham, , United Kingdom

GSK Investigational Site

Oxford, , United Kingdom

GSK Investigational Site

Plymouth, , United Kingdom

GSK Investigational Site

Stoke-on-Trent, , United Kingdom

Countries

United States; Australia; Belgium; Brazil; Bulgaria; Canada; China; France; Germany; Greece; Hungary; Italy; Japan; Netherlands; Poland; Russia; South Korea; Spain; United Kingdom

References

Dimopoulos MA, Hungria VTM, Radinoff A, Delimpasi S, Mikala G, Masszi T, Li J, Capra M, Maiolino A, Pappa V, Chraniuk D, Osipov I, Leleu X, Low M, Matsumoto M, Sule N, Li M, McKeown A, He W, Bright S, Currie B, Perera S, Boyle J, Roy-Ghanta S, Opalinska J, Weisel K. Efficacy and safety of single-agent belantamab mafodotin versus pomalidomide plus low-dose dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM-3): a phase 3, open-label, randomised study. Lancet Haematol. 2023 Oct;10(10):e801-e812. doi: 10.1016/S2352-3026(23)00243-0.

Reference Type: DERIVED

PMID: 37793771 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-004252-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

207495

Identifier Type: -

Identifier Source: org_study_id