A Study of Belantamab Mafodotin Administered in Combination With Lenalidomide and Dexamethasone (BRd) Versus Daratumumab, Lenalidomide, and Dexamethasone (DRd) in Participants With Newly Diagnosed Multiple Myeloma (NDMM) Who Are Ineligible for Autologous Stem Cell Transplantation (TI-NDMM)

NCT06679101 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: 2148282024-516030-35
• Study Type: interventional
• Target: 520
• Locations: 24 countries
• Sites: 181

Brief Summary

The purpose of this Phase 3 study is to evaluate if BRd prolongs progression free survival (PFS) and/or improves minimal residual disease (MRD) negative status compared with DRd in participants with TI-NDMM.

Conditions

Multiple Myeloma; Newly Diagnosed Multiple Myeloma

Keywords

Multiple myeloma; Belantamab mafodotin; Lenalidomide; Dexamethasone; Daratumumab; Transplant-ineligible; DREAMM-10

Outcome Measures

Primary Outcomes (2)

• PFS

  Defined as the time from the date of randomization to the date of first documented PD per International Myeloma Working Group (IMWG) criteria by Independent Review Committee (IRC) or death from any cause in the absence of progression, whichever occurs first.

  Up to approximately 7 years

• Number of Participants Achieving MRD Negative Status

  Defined as achieving MRD negativity at 10\^-5 sensitivity threshold (1 nucleated tumor cell in 100,000 normal cells) assessed by next-generation sequencing (NGS) at least once during the time of confirmed complete response (CR) or better response per IMWG criteria by IRC.

  Up to approximately 7 years

Secondary Outcomes (14)

• Overall Survival (OS)

  Up to approximately 7 years

• PFS2

  Up to approximately 7 years

• Number of Participants Achieving CR or Better (CR+)

  Up to approximately 7 years

• Number of Participants Achieving Very Good Partial Response (VGPR) or Better

  Up to approximately 7 years

• Number of Participants Achieving Sustained MRD Negative Status

  Up to approximately 7 years

Study Arms (2)

Arm A: Belantamab Mafodotin + Lenalidomide + Dexamethasone

EXPERIMENTAL

Belantamab mafodotin, lenalidomide, and dexamethasone will be administered. Treatment will continue in both arms until progressive disease (PD), death, unacceptable toxicity, withdrawal of consent, or end of study, whichever occurs first.

Drug: Belantamab mafodotin; Drug: Lenalidomide; Drug: Dexamethasone

Arm B: Daratumumab + Lenalidomide + Dexamethasone

ACTIVE COMPARATOR

Daratumumab, lenalidomide, and dexamethasone will be administered. Treatment will continue in both arms until PD, death, unacceptable toxicity, withdrawal of consent, or end of study, whichever occurs first.

Drug: Lenalidomide; Drug: Dexamethasone; Drug: Daratumumab

Interventions

Belantamab mafodotin DRUG

Belantamab mafodotin will be administered.

Arm A: Belantamab Mafodotin + Lenalidomide + Dexamethasone

Lenalidomide DRUG

Lenalidomide will be administered.

Arm A: Belantamab Mafodotin + Lenalidomide + Dexamethasone; Arm B: Daratumumab + Lenalidomide + Dexamethasone

Dexamethasone DRUG

Dexamethasone will be administered.

Arm A: Belantamab Mafodotin + Lenalidomide + Dexamethasone; Arm B: Daratumumab + Lenalidomide + Dexamethasone

Daratumumab DRUG

Daratumumab will be administered.

Arm B: Daratumumab + Lenalidomide + Dexamethasone

Eligibility Criteria

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

You may qualify if:

• Is at least 18 or the legal age of consent in the jurisdiction in which the study is taking place, at the time of signing the informed consent.
• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in the protocol.
• NDMM with a requirement for treatment as documented per IMWG criteria.
• Must have at least 1 aspect of measurable disease, as assessed by the central laboratory, defined as 1 of the following:
• Urine M-protein excretion ≥200 mg/24 hours (≥0.2 g/24 hours) And/or
• Serum M-protein concentration ≥0.5 g/dL (≥5.0 g/L) And/or
• Serum free light-chain (FLC) assay: involved FLC level ≥10 mg/dL (≥100 mg/L) and an abnormal serum FLC ratio (\<0.26 or \>1.65).
• Newly diagnosed and not considered candidate for high-dose chemotherapy with autologous stem cell transplant (ASCT) due to any of the following:
• Presence of comorbid condition(s) likely to have a negative impact on tolerability of high-dose chemotherapy with ASCT.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Adequate organ system function as defined by the laboratory assessments.
• Male participants:
• Contraceptive use by men 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 Treatment Period and for at least 6 months after the last dose of study intervention to allow for clearance of any altered sperm:
• Refrain from donating fresh unwashed semen

You may not qualify if:

• Diagnosis of systemic amyloid light chain amyloidosis, Waldenstrom's disease, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, skin changes) or Primary Plasma Cell Leukemia (defined as circulating plasma cells \>5%).
• Prior systemic therapy for multiple myeloma, or smoldering multiple myeloma.
• Signs of meningeal or central nervous system involvement with multiple myeloma.
• Major surgery within 2 weeks prior to the first dose of study drugs or has not recovered fully from surgery. Kyphoplasty is not considered major surgery.
• 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.
• Current active liver or biliary disease (except for Gilbert's syndrome or asymptomatic gallstones, or otherwise stable chronic liver disease as per the investigator's assessment).
• Participants with previous or concurrent malignancies other than multiple myeloma are excluded. Exceptions are any other malignancy that has been considered medically stable for at least 2 years, after discussion with the GSK Medical Monitor. The participant must not be receiving active therapy, other than hormonal therapy for this disease.
• Evidence of cardiovascular risk including any of the following:
• Evidence of current clinically significant untreated arrhythmias, including clinically significant electrocardiogram abnormalities including second-degree (Mobitz Type II) or third-degree atrioventricular block.
• Recent history (within 3 months of screening) of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty or stenting, or bypass grafting.
• Class III or IV heart failure as defined by the New York Heart Association functional classification system.
• Known human immunodeficiency virus (HIV) infection, unless the participant can meet all of the following criteria:
• Established antiretroviral therapy for at least 4 weeks and HIV viral load \<400 copies/mL within Screening Period.
• CD4+ T-cell (CD4+) counts ≥350 cells/μL.
• No history of acquired immune deficiency syndrome-defining opportunistic infections within the last 12 months.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (181)

GSK Investigational Site

Mobile, Alabama, 36607, United States

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GSK Investigational Site

Phoenix, Arizona, 85054, United States

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GSK Investigational Site

Beverly Hills, California, 90211, United States

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GSK Investigational Site

Pasadena, California, 91105, United States

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GSK Investigational Site

Aurora, Colorado, 80012, United States

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GSK Investigational Site

Washington D.C., District of Columbia, 20007, United States

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GSK Investigational Site

Englewood, Florida, 34223, United States

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GSK Investigational Site

Lady Lake, Florida, 32159, United States

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GSK Investigational Site

Pembroke Pines, Florida, 33024, United States

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GSK Investigational Site

Saint Augustine, Florida, 32256, United States

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GSK Investigational Site

Atlanta, Georgia, 30322, United States

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GSK Investigational Site

Portland, Maine, 04074, United States

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GSK Investigational Site

Worcester, Massachusetts, 01655, United States

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GSK Investigational Site

Ann Arbor, Michigan, 48103, United States

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GSK Investigational Site

Detroit, Michigan, 48201, United States

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GSK Investigational Site

Billings, Montana, 59102, United States

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GSK Investigational Site

Hackensack, New Jersey, 07601, United States

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GSK Investigational Site

New York, New York, 10065, United States

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GSK Investigational Site

Stony Brook, New York, 11790, United States

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GSK Investigational Site

Charlotte, North Carolina, 28204, United States

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GSK Investigational Site

Winston-Salem, North Carolina, 27103, United States

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GSK Investigational Site

Columbus, Ohio, 43214, United States

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GSK Investigational Site

Providence, Rhode Island, 02903, United States

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GSK Investigational Site

Austin, Texas, 78705, United States

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GSK Investigational Site

Austin, Texas, 78712, United States

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GSK Investigational Site

Kingwood, Texas, 77339, United States

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GSK Investigational Site

San Antonio, Texas, 78240, United States

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GSK Investigational Site

Tyler, Texas, 75702, United States

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GSK Investigational Site

Fairfax, Virginia, 22031, United States

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GSK Investigational Site

Puyallup, Washington, 98373, United States

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GSK Investigational Site

Capital Federal, C1426ANZ, Argentina

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GSK Investigational Site

Ciudad Autonoma de Buenos Aire, 1414, Argentina

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GSK Investigational Site

Córdoba, Argentina

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GSK Investigational Site

Rosario, S2002, Argentina

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GSK Investigational Site

Viedma, R8500ACE, Argentina

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GSK Investigational Site

Gosford NSW, New South Wales, 2250, Australia

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GSK Investigational Site

Box Hill, Victoria, 3128, Australia

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GSK Investigational Site

Melbourne, Victoria, 3004, Australia

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GSK Investigational Site

Fitzroy, Australia

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GSK Investigational Site

Herston, Australia

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GSK Investigational Site

St Leonards, Australia

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GSK Investigational Site

Bruges, 8000, Belgium

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GSK Investigational Site

Brussels, 1200, Belgium

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GSK Investigational Site

Ghent, 9000, Belgium

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GSK Investigational Site

Hornu, 7301, Belgium

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GSK Investigational Site

Roeselare, 8800, Belgium

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GSK Investigational Site

Salvador, Estado de Bahia, Brazil

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GSK Investigational Site

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

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GSK Investigational Site

Barretos, 14784-400, Brazil

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GSK Investigational Site

Joinville, 89201-260, Brazil

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GSK Investigational Site

Porto Alegre, Brazil

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GSK Investigational Site

São Paulo, 01509-010, Brazil

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GSK Investigational Site

São Paulo, 04537-080, Brazil

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GSK Investigational Site

São Paulo, 05403-000, Brazil

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GSK Investigational Site

São Paulo, Brazil

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GSK Investigational Site

Teresina, 64049-200, Brazil

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GSK Investigational Site

Vitória, 29043-260, Brazil

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GSK Investigational Site

Saint John, New Brunswick, E2L 4L2, Canada

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GSK Investigational Site

Beijing, 100191, China

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GSK Investigational Site

Chengdu, 610072, China

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GSK Investigational Site

Chongqing, 400016, China

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GSK Investigational Site

Guangzhou, 510060, China

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GSK Investigational Site

Guangzhou, 510515, China

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GSK Investigational Site

Hangzhou, 310003, China

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GSK Investigational Site

Nanchang, 330000, China

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GSK Investigational Site

Nanchang, China

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GSK Investigational Site

Nanjing, 210008, China

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GSK Investigational Site

Shanghai, 200032, China

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GSK Investigational Site

Shanghia, 200080, China

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GSK Investigational Site

Shenzhen, 430022, China

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GSK Investigational Site

Shenzhen, 518039, China

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GSK Investigational Site

Tianjin, 300020, China

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GSK Investigational Site

Wenzhou, 325000, China

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GSK Investigational Site

Xi'an, 710004, China

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GSK Investigational Site

Ostrava, 708 52, Czechia

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GSK Investigational Site

Prague, 100 34, Czechia

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GSK Investigational Site

Bobigny, 93009, France

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GSK Investigational Site

Nantes, 44202, France

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GSK Investigational Site

Villejuif, 94805, France

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GSK Investigational Site

Jena, Europe, 7747, Germany

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GSK Investigational Site

Lübeck, Schleswig-Holstein, 23538, Germany

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GSK Investigational Site

Chemnitz, 9116, Germany

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GSK Investigational Site

Cologne, 50937, Germany

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GSK Investigational Site

Dresden, 01307, Germany

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GSK Investigational Site

Hamburg, 20246, Germany

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GSK Investigational Site

Hanover, 30625, Germany

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GSK Investigational Site

Mainz, 55131, Germany

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GSK Investigational Site

Würzburg, 97080, Germany

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GSK Investigational Site

Alexandroupoli, 68 100, Greece

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GSK Investigational Site

Athens, 106 76, Greece

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GSK Investigational Site

Athens, 115 28, Greece

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GSK Investigational Site

Athens, Greece

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GSK Investigational Site

Pátrai, 26504, Greece

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GSK Investigational Site

Thessaloniki, 54007, Greece

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GSK Investigational Site

Ahmedabad, 380009, India

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GSK Investigational Site

Bangalore, 560054, India

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GSK Investigational Site

Hyderabad, 500033, India

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GSK Investigational Site

Kolkata, 700014, India

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GSK Investigational Site

Kolkata, 700156, India

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GSK Investigational Site

Pune, 411001, India

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GSK Investigational Site

Sushrut Hospital and Research, 400071, India

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GSK Investigational Site

Dublin, D09V2N0, Ireland

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GSK Investigational Site

Galway, Ireland

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GSK Investigational Site

Waterford, Ireland

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GSK Investigational Site

Beersheba, 84101, Israel

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GSK Investigational Site

Jerusalem, 91120, Israel

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GSK Investigational Site

Koranit, 2018100, Israel

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GSK Investigational Site

Petah Tikva, 49100, Israel

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GSK Investigational Site

Tel Aviv, 64239, Israel

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GSK Investigational Site

Ancona, Italy

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GSK Investigational Site

Catania, Italy

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GSK Investigational Site

Meldola FC, 47014, Italy

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GSK Investigational Site

Palermo, 90127, Italy

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GSK Investigational Site

Pavia, 27100, Italy

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GSK Investigational Site

Pisa, Italy

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GSK Investigational Site

Roma, 00161, 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

Ehime, 790-0024, Japan

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GSK Investigational Site

Ehime, 790-8524, Japan

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GSK Investigational Site

Fukuoka, 815-8555, Japan

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GSK Investigational Site

Fukushima, 960-1295, Japan

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GSK Investigational Site

Gunma, 371-8511, Japan

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GSK Investigational Site

Hyōgo, 660-8550, Japan

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GSK Investigational Site

Hyōgo, 670-8540, Japan

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GSK Investigational Site

Ibaraki, 300-0028, Japan

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GSK Investigational Site

Ishikawa, 920-8641, Japan

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GSK Investigational Site

Kanagawa, 211-8510, Japan

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GSK Investigational Site

Miyagi, 983-8520, Japan

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GSK Investigational Site

Nara, 632-8552, Japan

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GSK Investigational Site

Numakunai, 028-3695, Japan

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GSK Investigational Site

Osaka, 589-8511, Japan

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GSK Investigational Site

Sapporo, 003-0006, Japan

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GSK Investigational Site

Suita, 565-0871, Japan

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GSK Investigational Site

Tokyo, 105-8471, Japan

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GSK Investigational Site

Yamagata, 990-9585, Japan

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GSK Investigational Site

Bergen, 5021, Norway

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GSK Investigational Site

Lrenskog, 1470, Norway

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GSK Investigational Site

Oslo, Norway

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GSK Investigational Site

Lodz, 93-513, Poland

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GSK Investigational Site

Lublin, 20-954, Poland

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GSK Investigational Site

Lublin, Poland

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GSK Investigational Site

Warsaw, 02-781, Poland

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GSK Investigational Site

Wałbrzych, 58-309, Poland

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GSK Investigational Site

Kuils River, 7580, South Africa

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GSK Investigational Site

Pretoria, 0181, South Africa

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GSK Investigational Site

Hwasun, 519-763, South Korea

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GSK Investigational Site

Jeonju, 561-712, South Korea

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GSK Investigational Site

Seoul, 03080, South Korea

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GSK Investigational Site

Seoul, 03722, South Korea

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GSK Investigational Site

Seoul, 06351, South Korea

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GSK Investigational Site

Seoul, 06591, South Korea

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GSK Investigational Site

Seoul, 138-736, South Korea

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GSK Investigational Site

Ulsan, 44033, South Korea

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GSK Investigational Site

Badalona, Spain

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GSK Investigational Site

Barcelona, 08035, Spain

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GSK Investigational Site

Gijón, 33394, Spain

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GSK Investigational Site

Madrid, 28007, Spain

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GSK Investigational Site

Madrid, 28041, Spain

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GSK Investigational Site

Madrid, Spain

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GSK Investigational Site

Málaga, 29010, Spain

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GSK Investigational Site

Murcia, 30120, Spain

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GSK Investigational Site

Salamanca, Spain

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GSK Investigational Site

Santander, 39011, Spain

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GSK Investigational Site

Valladolid, 47003, Spain

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GSK Investigational Site

Kaohsiung City, 807, Taiwan

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GSK Investigational Site

Taichung, 407219, Taiwan

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GSK Investigational Site

Tainan, 704, Taiwan

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GSK Investigational Site

Taipei, 10002, Taiwan

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GSK Investigational Site

Taoyuan District, 33305, Taiwan

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GSK Investigational Site

Samsun, Atakum, 55200, Turkey (Türkiye)

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GSK Investigational Site

Kocaeli, İzmit, 41001, Turkey (Türkiye)

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GSK Investigational Site

Ankara, Yenimahalle, 06170, Turkey (Türkiye)

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GSK Investigational Site

Adana, 01330, Turkey (Türkiye)

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GSK Investigational Site

Ankara, 06680, Turkey (Türkiye)

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GSK Investigational Site

Sisli - Istanbul, 34381, Turkey (Türkiye)

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GSK Investigational Site

Leicester, LE1 5WW, United Kingdom

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GSK Investigational Site

Middlesbrough, TS4 3BW, United Kingdom

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GSK Investigational Site

Oxford, OX3 7LE, United Kingdom

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GSK Investigational Site

Plymouth, PL6 8DH, United Kingdom

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GSK Investigational Site

Wolverhampton, WV10 0QP, United Kingdom

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MeSH Terms

Conditions

Multiple Myeloma

Interventions

belantamab mafodotin; Lenalidomide; Dexamethasone; daratumumab

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)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Central Study Contacts

US GSK Clinical Trials Call Center

CONTACT

877-379-3718; GSKClinicalSupportHD@gsk.com

EU GSK Clinical Trials Call Center

CONTACT

+44 (0) 20 89904466; GSKClinicalSupportHD@gsk.com

Study Design

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

Study Record Dates

• First Submitted: November 6, 2024
• First Posted: November 7, 2024
• Study Start: December 16, 2024
• Primary Completion (Estimated): April 28, 2031
• Study Completion (Estimated): April 28, 2031
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (9); ZA (2); CZ (2); US (30); CN (16); IT (7); GB (5); FR (3); TU (6); AU (6); AR (5); IL (5); TW (5); PL (5); JP (20); NO (3); IN (7); GR (6); BR (11); BE (5); IE (3); CA (1); ES (11); KR (8)