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

NCT04162210 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 2 other identifiers: 2074952018-004252-38
• Study Type: interventional
• Target: 325
• Locations: 19 countries
• Sites: 102

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

Keywords

Belantamab mafodotin; Pomalidomide; Dexamethasone; Relapsed/Refractory Multiple Myeloma; Driving Excellence in Approaches to Multiple Myeloma 3 (DREAMM 3)

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS) Based on Investigator-assessed Response as Per International Myeloma Working Group (IMWG)

  PFS is time from randomization until earliest date of progressive disease (PD), or death due to any cause per investigator-assessed response per IMWG. PD is ≥25% increase from nadir in any of following: serum M-protein (absolute increase ≥0.5 gram per deciliter \[g/dL\]),urine M-protein(absolute increase ≥200 mg/24hr),difference between involved/uninvolved FLC levels (absolute increase \>10 mg/dL) in patients without measurable serum and urine M-protein levels, or bone marrow plasma-cell percentage irrespective of baseline status (absolute increase ≥10%) in patients without measurable serum and urine M-protein levels and without measurable involved FLC levels; appearance of new lesion,≥50% increase in longest diameter of a lesion previously measured \>1cm in short axis, or ≥50% increase from nadir in sum of products of two longest perpendicular diameters of more than 1 lesion; ≥50% increase in circulating plasma cells (minimum of 200 cells/microliter) if this is only measure of disease.

  Up to 27 months

Secondary Outcomes (34)

• Overall Survival (OS)

  60 months

• Overall Response Rate (ORR)

  Up to 55 months

• Clinical Benefit Rate (CBR)

  Up to 55 months

• Duration of Response (DoR)

  Up to 55 months

• Time to Response (TTR)

  Up to 55 months

Study Arms (2)

Participants receiving Belantamab mafodotin

EXPERIMENTAL

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

Drug: Belantamab mafodotin

Participants receiving pom/dex

ACTIVE COMPARATOR

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.

Drug: Pom/dex (Pomalidomide plus low dose Dexamethasone)

Interventions

Belantamab mafodotin DRUG

Belantamab mafodotin will be administered.

Participants receiving Belantamab mafodotin

Pom/dex (Pomalidomide plus low dose Dexamethasone) DRUG

Pomalidomide and Dexamethasone will be administered.

Participants receiving pom/dex

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (102)

GSK Investigational Site

Tucson, Arizona, 85715, United States

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GSK Investigational Site

Pueblo, Colorado, 81008, United States

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GSK Investigational Site

Detroit, Michigan, 48202, United States

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GSK Investigational Site

Omaha, Nebraska, 68130, United States

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GSK Investigational Site

Clifton Park, New York, 12065, United States

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GSK Investigational Site

Cincinnati, Ohio, 45236, United States

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GSK Investigational Site

Corvallis, Oregon, 97330, United States

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GSK Investigational Site

Eugene, Oregon, 97401, United States

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GSK Investigational Site

Tyler, Texas, 75702, United States

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GSK Investigational Site

Milwaukee, Wisconsin, 53226, United States

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GSK Investigational Site

St Leonards, New South Wales, 2065, Australia

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GSK Investigational Site

Hobart, Tasmania, 7000, Australia

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GSK Investigational Site

Fitzroy, Victoria, 3065, Australia

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GSK Investigational Site

Geelong, Victoria, 3220, Australia

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GSK Investigational Site

Nedlands, Western Australia, 6009, Australia

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GSK Investigational Site

Bruges, 8000, Belgium

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GSK Investigational Site

Brussels, 1090, Belgium

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GSK Investigational Site

Brussels, 1200, Belgium

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GSK Investigational Site

Edegem, 2650, Belgium

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GSK Investigational Site

Kortrijk, 8500, Belgium

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GSK Investigational Site

Yvoir, 5530, Belgium

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GSK Investigational Site

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

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GSK Investigational Site

Curitiba, 80530-010, Brazil

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GSK Investigational Site

Fortaleza, 60115-281, Brazil

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GSK Investigational Site

Porto Alegre, 90110-270, Brazil

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GSK Investigational Site

Rio de Janeiro, 22793-080, Brazil

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GSK Investigational Site

São Paulo, 01321001, Brazil

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GSK Investigational Site

São Paulo, 01509-900, Brazil

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GSK Investigational Site

São Paulo, 04537-080, Brazil

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GSK Investigational Site

São Paulo, 05651-901, Brazil

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GSK Investigational Site

Sofia, 1606, Bulgaria

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GSK Investigational Site

Edmonton, Alberta, T6G 1Z2, Canada

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GSK Investigational Site

Beijing, 100000, China

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GSK Investigational Site

Beijing, 100050, China

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GSK Investigational Site

Beijing, 100730, China

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GSK Investigational Site

Chengdu, 610041, China

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Hangzhou, 310009, China

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GSK Investigational Site

Nanchang, 330006, China

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Shenzhen, 518029, China

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GSK Investigational Site

Tianjin, 300020, China

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Tianjin, 300060, China

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GSK Investigational Site

Xuzhou, 221006, China

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GSK Investigational Site

Zhengzhou, 450052, China

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GSK Investigational Site

Le Mans, 72015, France

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Montpellier, 34295, France

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GSK Investigational Site

Poitiers, 86021, France

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Berlin, 13125, Germany

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GSK Investigational Site

Tübingen, 72076, Germany

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GSK Investigational Site

Athens, 10676, Greece

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GSK Investigational Site

Athens, 115 28, Greece

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GSK Investigational Site

Haidari - Athens, 12462, Greece

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GSK Investigational Site

Larissa, 41 110, Greece

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GSK Investigational Site

Pátrai, 26500, Greece

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GSK Investigational Site

Thessaloniki, 54007, Greece

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GSK Investigational Site

Thessaloniki, 57010, Greece

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GSK Investigational Site

Budapest, 1083, Hungary

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GSK Investigational Site

Budapest, 1088, Hungary

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GSK Investigational Site

Budapest, 1097, Hungary

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Debrecen, 4012, Hungary

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GSK Investigational Site

Kaposvár, 7400, Hungary

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GSK Investigational Site

Nyíregyháza, 4400, Hungary

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GSK Investigational Site

Brescia, 25123, Italy

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Catanzaro, 88100, Italy

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GSK Investigational Site

Milan, 20122, Italy

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Milan, 20141, Italy

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Pavia, 27100, Italy

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Perugia, 05100, Italy

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Ravenna, 48123, Italy

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Roma, 00161, Italy

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GSK Investigational Site

San Giovanni Rotondo FG, 71013, Italy

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GSK Investigational Site

Siena, 53100, Italy

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GSK Investigational Site

Shibuya-Ku, Tokyo, 150-8935, Japan

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GSK Investigational Site

Aichi, 467-8602, Japan

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GSK Investigational Site

Chiba, 277-8567, Japan

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GSK Investigational Site

Ehime, 790-8524, Japan

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GSK Investigational Site

Fukushima, 960-1295, Japan

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GSK Investigational Site

Gifu, 503-8502, Japan

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GSK Investigational Site

Gunma, 377-0280, Japan

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GSK Investigational Site

Hokkaido, 060-8648, Japan

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GSK Investigational Site

Kyoto, 602-8566, Japan

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GSK Investigational Site

Kyoto, 603-8151, Japan

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GSK Investigational Site

Osaka, 565-0871, Japan

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GSK Investigational Site

Tokyo, 108-8639, Japan

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GSK Investigational Site

Amersfoort, 3813 TZ, Netherlands

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GSK Investigational Site

Gdansk, 80-214, Poland

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GSK Investigational Site

Kaluga, 248007, Russia

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GSK Investigational Site

Gyeonggi-do, 10408, South Korea

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GSK Investigational Site

Hwasun, 58128, South Korea

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GSK Investigational Site

Incheon, 21565, South Korea

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GSK Investigational Site

Seongnam-si Gyeonggi-do, 13620, South Korea

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GSK Investigational Site

Seoul, 03080, South Korea

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GSK Investigational Site

Seoul, 05505, South Korea

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GSK Investigational Site

Seoul, 06591, South Korea

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GSK Investigational Site

Barcelona, 08036, Spain

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GSK Investigational Site

Barcelona, 08916, Spain

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GSK Investigational Site

L'Hospitalet de Llobrega, 08908, Spain

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GSK Investigational Site

Málaga, 29004, Spain

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GSK Investigational Site

PamplonaNavarra, 31008, Spain

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GSK Investigational Site

Pozuelo de AlarcOn Madr, 28223, Spain

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GSK Investigational Site

Santiago de Compostela, 15706, Spain

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GSK Investigational Site

Dundee, DD1 9SY, United Kingdom

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GSK Investigational Site

London, W12 0NN, United Kingdom

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Related Publications (1)

• 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.

  PMID: 37793771 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

belantamab mafodotin; pomalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Model Details: This is an open-label, randomized and multi-center study

Study Record Dates

• First Submitted: November 11, 2019
• First Posted: November 14, 2019
• Study Start: April 2, 2020
• Primary Completion: September 12, 2022
• Study Completion (Estimated): March 11, 2027
• Last Updated: March 31, 2026
• Results First Posted: October 6, 2023

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (11); HU (6); CA (1); BU (1); AU (5); GR (7); RU (1); DE (2); NL (1); PL (1); JP (12); US (10); BR (9); KR (7); GB (2); BE (6); ES (7); FR (3); IT (10)