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)

Last updated: May 14, 2025
Sponsor: GlaxoSmithKline
Overall Status: Active - Recruiting

Phase

3

Condition

Multiple Myeloma

Bone Neoplasm

Leukemia

Treatment

Belantamab mafodotin

Dexamethasone

Lenalidomide

Clinical Study ID

NCT06679101
214828
2024-516030-35
  • Ages > 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Is at least 18 or the legal age of consent in the jurisdiction in which the study istaking place, at the time of signing the informed consent.

  2. Capable of giving signed informed consent, which includes compliance with therequirements and restrictions listed in the informed consent form and in theprotocol.

  3. NDMM with a requirement for treatment as documented per IMWG criteria.

  4. Must have at least 1 aspect of measurable disease, as assessed by the centrallaboratory, defined as 1 of the following:

  5. Urine M-protein excretion ≥200 mg/24 hours (≥0.2 g/24 hours) And/or

  6. Serum M-protein concentration ≥0.5 g/dL (≥5.0 g/L) And/or

  7. 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).

  8. Newly diagnosed and not considered candidate for high-dose chemotherapy withautologous stem cell transplant (ASCT) due to any of the following:

  9. ≥70 years of age, OR

  10. Age 18 to 69 years with presence of comorbid condition(s) likely to have anegative impact on tolerability of high-dose chemotherapy with ASCT, (or forwhom national guidelines do not permit transplant due to a cut-off age below 70years), OR

  11. Who refuse high-dose chemotherapy with ASCT as an initial treatment.

  12. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

  13. Adequate organ system function as defined by the laboratory assessments.

  14. Male participants:

  • Contraceptive use by men should be consistent with local regulations regardingthe methods of contraception for those participating in clinical studies.

  • Male participants are eligible to participate if they agree to the followingduring the Treatment Period and for at least 6 months after the last dose ofstudy intervention to allow for clearance of any altered sperm:

  • Refrain from donating fresh unwashed semen PLUS either:

  • Be abstinent from heterosexual intercourse as their preferred and usuallifestyle (abstinent on a long term and persistent basis) and agree to remainabstinent. OR

  • Must agree to use contraception/barrier as detailed below

  • Agree to use a male condom, even if they have undergone a successful vasectomy,and female partner to use an additional highly effective contraceptive methodwith a failure rate of <1% per year when having sexual intercourse with a womanof childbearing potential (WOCBP) who is not currently pregnant. Maleparticipants should also use a condom when having sexual intercourse withpregnant females.

  1. Female participants
  • Contraceptive use by women should be consistent with local regulationsregarding the methods of contraception for those participating in clinicalstudies.

  • A female participant is eligible to participate if she is not pregnant orbreastfeeding, and at least 1 of the following conditions applies:

  • Is not a WOCBP OR

  • Is a WOCBP and using a contraceptive method that is highly effective (with afailure rate of <1% per year), preferably with low user dependency during theTreatment Period and for 4 months after the last dose of study intervention andagrees not to donate eggs (ova, oocytes) for the purpose of reproduction duringthis period. The investigator should evaluate the effectiveness of thecontraceptive method in relationship to the first dose of study intervention.

  • A WOCBP must have 2 negative highly sensitive serum pregnancy tests beforestarting treatment, the first may be performed within 14 days from C1D1, thesecond within 24 hours before the first dose of study intervention.

  • Should pregnancy occur in a female on treatment or the female partner of a maleon treatment, treatment must be stopped, and it is advised to seek advice froma physician specialized or experienced in teratology.

Exclusion

Exclusion Criteria:

  1. Diagnosis of systemic amyloid light chain amyloidosis, Waldenstrom's disease, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferativedisorder, skin changes) or Primary Plasma Cell Leukemia (defined as circulatingplasma cells >5%).

  2. Prior systemic therapy for multiple myeloma, or smoldering multiple myeloma.

  3. Signs of meningeal or central nervous system involvement with multiple myeloma.

  4. Major surgery within 2 weeks prior to the first dose of study drugs or has notrecovered fully from surgery. Kyphoplasty is not considered major surgery.

  5. Any serious and/or unstable pre-existing medical, psychiatric disorder or otherconditions (including lab abnormalities) that could interfere with participant'ssafety, obtaining informed consent, or compliance with study procedures.

  6. Current active liver or biliary disease (except for Gilbert's syndrome orasymptomatic gallstones, or otherwise stable chronic liver disease as per theinvestigator's assessment).

  7. Participants with previous or concurrent malignancies other than multiple myelomaare excluded. Exceptions are any other malignancy that has been considered medicallystable for at least 2 years, after discussion with the GSK Medical Monitor. Theparticipant must not be receiving active therapy, other than hormonal therapy forthis disease.

  8. Evidence of cardiovascular risk including any of the following:

  9. Evidence of current clinically significant untreated arrhythmias, includingclinically significant electrocardiogram abnormalities including second-degree (Mobitz Type II) or third-degree atrioventricular block.

  10. Recent history (within 3 months of screening) of myocardial infarction, acutecoronary syndromes (including unstable angina), coronary angioplasty orstenting, or bypass grafting.

  11. Class III or IV heart failure as defined by the New York Heart Associationfunctional classification system.

  12. Known human immunodeficiency virus (HIV) infection, unless the participant can meetall of the following criteria:

  13. Established antiretroviral therapy for at least 4 weeks and HIV viral load <400copies/mL within Screening Period.

  14. CD4+ T-cell (CD4+) counts ≥350 cells/μL.

  15. No history of acquired immune deficiency syndrome-defining opportunisticinfections within the last 12 months.

  16. 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 studyintervention unless the participant can meet the following criteria:

  17. RNA test negative.

  18. Successful antiviral treatment (usually 8 weeks duration) is required, followedby a negative hepatitis C viral load RNA test after a washout period of atleast 4 weeks.

  19. Participants with hepatitis B will be excluded unless the defined criteria can bemet.

  20. Current corneal epithelial disease except for mild punctate keratopathy.

  21. Intolerance or contraindications to antiviral prophylaxis.

  22. Unable to tolerate antithrombotic prophylaxis.

  23. Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction todrugs chemically related to belantamab mafodotin, or any of the components of thestudy intervention.

  24. Plasmapheresis within 7 days prior to the first dose of study intervention.

  25. Participants must not have received a live or live-attenuated vaccine within 30 daysprior to first dose of belantamab mafodotin.

Study Design

Total Participants: 520
Treatment Group(s): 4
Primary Treatment: Belantamab mafodotin
Phase: 3
Study Start date:
December 27, 2024
Estimated Completion Date:
April 06, 2032

Connect with a study center

  • GSK Investigational Site

    Capital Federal, C1426ANZ
    Argentina

    Active - Recruiting

  • GSK Investigational Site

    Ciudad Autonoma de Buenos Aire, 1414
    Argentina

    Active - Recruiting

  • GSK Investigational Site

    Rosario, S2002
    Argentina

    Active - Recruiting

  • GSK Investigational Site

    Viedma, R8500ACE
    Argentina

    Active - Recruiting

  • GSK Investigational Site

    Gosford NSW, New South Wales 2250
    Australia

    Active - Recruiting

  • GSK Investigational Site

    Fitzroy,
    Australia

    Active - Recruiting

  • GSK Investigational Site

    Beijing, 100191
    China

    Active - Recruiting

  • GSK Investigational Site

    Shanghia, 200080
    China

    Active - Recruiting

  • GSK Investigational Site

    Tianjin, 300020
    China

    Active - Recruiting

  • GSK Investigational Site

    Aichi, 467-8602
    Japan

    Active - Recruiting

  • GSK Investigational Site

    Ehime, 790-0024
    Japan

    Active - Recruiting

  • GSK Investigational Site

    Fukushima, 960-1295
    Japan

    Active - Recruiting

  • GSK Investigational Site

    Gunma, 371-8511
    Japan

    Active - Recruiting

  • GSK Investigational Site

    Hyogo, 660-8550
    Japan

    Active - Recruiting

  • GSK Investigational Site

    Ibaraki, 300-0028
    Japan

    Active - Recruiting

  • GSK Investigational Site

    Iwate, 028-3695
    Japan

    Active - Recruiting

  • GSK Investigational Site

    Miyagi, 983-8520
    Japan

    Active - Recruiting

  • GSK Investigational Site

    Nara, 632-8552
    Japan

    Active - Recruiting

  • GSK Investigational Site

    Sapporo, 003-0006
    Japan

    Active - Recruiting

  • GSK Investigational Site

    Suita, 565-0871
    Japan

    Active - Recruiting

  • GSK Investigational Site

    Tokyo, 105-8471
    Japan

    Active - Recruiting

  • GSK Investigational Site

    Yamagata, 990-9585
    Japan

    Active - Recruiting

  • GSK Investigational Site

    Hwasun, 519-763
    Korea, Republic of

    Active - Recruiting

  • GSK Investigational Site

    Jeonju, 561-712
    Korea, Republic of

    Active - Recruiting

  • GSK Investigational Site

    Seoul, 03722
    Korea, Republic of

    Active - Recruiting

  • GSK Investigational Site

    Ulsan, 44033
    Korea, Republic of

    Active - Recruiting

  • GSK Investigational Site

    Lublin,
    Poland

    Active - Recruiting

  • GSK Investigational Site

    Madrid, 28041
    Spain

    Active - Recruiting

  • GSK Investigational Site

    Murcia, 30120
    Spain

    Active - Recruiting

  • GSK Investigational Site

    Valladolid, 47003
    Spain

    Active - Recruiting

  • GSK Investigational Site

    Kaohsiung, 807
    Taiwan

    Active - Recruiting

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