Belantamab Mafodotin or Daratumumab With Bortezomib, Lenalidomide and Dexamethasone for Newly Diagnosed Multiple Myeloma

NCT ID: NCT07285239

Last Updated: 2025-12-16

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 500 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-05-31
• Study Completion Date: 2034-04-30

Brief Summary

Eligible participants with newly diagnosed myeloma who are not considered eligible for bone marrow transplant will be enrolled. Participants will be randomized to either belantamab mafodotin or daratumumab given in combination with bortezomib, lenalidomide and dexamethasone. Treatment will continue until disease progression, unacceptable side effects or withdrawal of consent.

Belantamab mafodotin is a targeted cancer treatment that works against multiple myeloma cells. It combines a homing device (an antibody) with a powerful cell-killing drug (a toxin), delivering the toxin directly to cancer cells while largely sparing healthy cells.

Minimal residual disease (MRD) testing will be done on bone marrow samples obtained standardly during your treatment. MRD shows whether a very small number of cancer cells can still be detected after treatment, even if standard lab tests shows no signs of cancer.

The purpose of this study is to evaluate if belantamab mafodotin, bortezomib, lenalidomide and dexamethasone (BVRd) improves minimal residual disease (MRD) negative status and/or prolongs progression-free survival (PFS) compared with daratumumab, bortezomib, lenalidomide and dexamethasone (DVRd) in participants with newly diagnosed multiple myeloma.

Detailed Description

This proposed Phase III multicenter, study is a randomized (1:1), open-label trial designed to show belantamab mafodotin in combination with bortezomib, lenalidomide and dexamethasone (VRd) will lead to higher minimal residual disease (MRD) negativity rate compared with daratumumab in combination with VRd in transplant ineligible newly diagnosed multiple myeloma (TI-NDMM). In addition, progression-free survival (PFS) will also be longer on the high-risk enriched population and the subgroup of high-risk cytogenetic participants.

After enrolling the first 400 patients, the study will limit accrual to patients with high risk NDMM to allow for enrichment of this subgroup of patients.

Belantamab mafodotin is a monoclonal antibody that targets B-cell maturation antigen (BCMA), a protein expressed on the surface of plasma cells, and releases a cytotoxic agent called Monomethyl auristatin F, which destroys the plasma cells.

International Myeloma Working Group (IMWG) criteria will be used for disease response.

MRD samples will be obtained on standard of care bone marrow procedures. MRD testing will be performed on samples at time of screening, suspected complete response (sCR), after confirmed CR at applicable time points from Cycle1, Day 1 at 6, 12, 18 (optional), 24, 30 (optional) and 36 months then annually until progression. MRD testing will not be performed in real-time for this study. Bone marrow samples will also be obtained for future research at screening and time of progression.

Research peripheral blood samples will be obtained to measure levels of belantamab mafodotin in the blood, immune responses or antibodies to belantamab mafodotin for patients receiving belantamab mafodotin. In addition, research blood samples will be obtained on all patients to measure soluble B-cell maturation antigen (sBCMA) to help diagnose, monitor treatment effectiveness, and predict the prognosis of multiple myeloma.

Patient-reported outcomes will also be performed.

Conditions

Multiple Myeloma

Study Design

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

Study Groups

Arm A: Belantamab Mafodotin

Belantamab mafodotin in combination with bortezomib, lenalidomide and dexamethasone (VRd) until progression, unacceptable toxicity or participant withdrawal. 1 cycle = 28 days.

Group Type: EXPERIMENTAL

Arm A: Belantamab Mafodotin

Intervention Type: DRUG

1.9 milligram/kilogram (mg/kg) intravenous (IV) will be administered every 8 weeks for first 24 weeks (Cycles 1-3), then 1.9 mg/kg every 12 weeks (Cycles 4+) until progression, unacceptable toxicity or participant withdrawal

Bortezomib

Intervention Type: DRUG

1.3 milligrams per square meter (mg /m²) SC on days 1, 8 and 15 of every 28 day bortezomib treatment cycle for 8 cycles

Lenalidomide

Intervention Type: DRUG

25 mg orally (PO) Days 1-21 of every 28 day lenalidomide treatment cycle.

Dexamethasone

Intervention Type: DRUG

40 mg PO on Days 1, 8, 15, and 22 of each 28-day cycle

Arm B:

Daratumumab in combination with bortezomib, lenalidomide and dexamethasone (VRd) until progression, unacceptable toxicity or participant withdrawal. 1 cycle = 28 days.

Group Type: ACTIVE_COMPARATOR

Arm B: Daratumumab Hyaluronidase

Intervention Type: DRUG

1800 mg subcutaneous (SC) will be administered weekly from Week 1-8 (Cycles 1 and 2), every 2 weeks from Week 9-24 (Cycles 3-6), and every 4 weeks from Week 25 (Cycles 7+) onwards until progression, unacceptable toxicity or participant withdrawal

Bortezomib

Intervention Type: DRUG

1.3 milligrams per square meter (mg /m²) SC on days 1, 8 and 15 of every 28 day bortezomib treatment cycle for 8 cycles

Lenalidomide

Intervention Type: DRUG

25 mg orally (PO) Days 1-21 of every 28 day lenalidomide treatment cycle.

Dexamethasone

Intervention Type: DRUG

40 mg PO on Days 1, 8, 15, and 22 of each 28-day cycle

Interventions

Arm A: Belantamab Mafodotin

1.9 milligram/kilogram (mg/kg) intravenous (IV) will be administered every 8 weeks for first 24 weeks (Cycles 1-3), then 1.9 mg/kg every 12 weeks (Cycles 4+) until progression, unacceptable toxicity or participant withdrawal

Intervention Type: DRUG

Arm B: Daratumumab Hyaluronidase

1800 mg subcutaneous (SC) will be administered weekly from Week 1-8 (Cycles 1 and 2), every 2 weeks from Week 9-24 (Cycles 3-6), and every 4 weeks from Week 25 (Cycles 7+) onwards until progression, unacceptable toxicity or participant withdrawal

Intervention Type: DRUG

Bortezomib

1.3 milligrams per square meter (mg /m²) SC on days 1, 8 and 15 of every 28 day bortezomib treatment cycle for 8 cycles

Intervention Type: DRUG

Lenalidomide

25 mg orally (PO) Days 1-21 of every 28 day lenalidomide treatment cycle.

Intervention Type: DRUG

Dexamethasone

40 mg PO on Days 1, 8, 15, and 22 of each 28-day cycle

Intervention Type: DRUG

Other Intervention Names

GSK2857916; Blenrep; Belamaf; DARZALEX FASPRO™; Velcade®; Revlimid®; Decadron

Eligibility Criteria

Inclusion Criteria

• Patient must have measurable or evaluable disease as defined by having one or more of the following, obtained within 28 days prior to randomization.

• ≥ 1g/dL monoclonal protein (M-protein) on serum protein electrophoresis
• Involved free light chain ≥ 10 mg/dL or ≥ 100 mg/L AND abnormal serum immunoglobulin kappa to lambda free light chain ratio (<0.26 or >1.65)
• ≥ 200 mg/24 hours of monoclonal protein on a 24-hour urine protein electrophoresis
• Monoclonal bone marrow plasmacytosis ≥ 30% (evaluable disease)
• Patient must be ≥ 18 years of age.
• Patient must have an Eastern Cooperative Group (ECOG) Performance Status (PS) of 0-2 (PS 3 allowed if secondary to pain).
• Patient must have the ability to understand and willingness to sign a written informed consent document.
• Patient must be willing to provide bone marrow (aspirate and/or biopsy) and blood samples for determination of International Myeloma Society (IMS) risk status and for research.
• Patient must have received no more than one cycle (28 days or less) of prior chemotherapy and no more than 160 mg of prior dexamethasone (or equivalent dose of prednisone) for treatment of symptomatic myeloma. Prior radiation therapy to symptomatic lesions is allowed provided there is no residual toxicity related to radiation and blood counts meet the study requirements.
• Patient must have a Serum Protein Electrophoresis (SPEP), Urine Protein Electrophoresis (UPEP), and serum Free Light Chain (FLC) assay performed within 28 days prior to registration. In addition, a bone marrow biopsy and/or aspirate is required within 28 days prior to registration if measurable disease is only present in bone marrow. Otherwise, a bone marrow examination must have been performed within 90 days prior to registration.
• Patient must have adequate organ function and marrow function as defined below, obtained ≤ 2 weeks prior to registration.

• Absolute Neutrophil Count (ANC) ≥ 1000/microliter (mcL)
• Platelets ˃75,000/mcL
• Creatinine clearance (CrCl) ≥ 30 mL/min
• Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 3x upper limit of normal (ULN)
• Total Bilirubin ≤ 1.5x ULN or ≤ 3x ULN for patients with documented Gilbert's disease
• Patient must agree to register to the mandatory lenalidomide (Revlimid) Risk Evaluation and Mitigation Strategy (REMS) program and be willing and able to comply with the requirements of the REMS program.
• Patient must not be pregnant or breast-feeding due to the potential harm and teratogenic effects to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used.
• Patient must not expect to conceive or father children by using an accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study, and for 3 months after the last dose of protocol treatment.
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial.
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
• Patient with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association (NYHA) Functional Classification. To be eligible for this trial, patient must be class 2 or better.
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• Patients must not have peripheral neuropathy ≥ Grade 2 on clinical examination or Grade 1 with pain at time of registration.
• Patients must not have any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
• Patient may have a history of current or previous deep vein thrombosis (DVT) or pulmonary embolism (PE) but must be willing to take some form of anti-coagulation as prophylaxis if they are not currently on full-dose anticoagulation.
• Patients must not have any known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal antibodies or human proteins, or their excipients, or known sensitivity to mammalian-derived products.
• Patients must not have current corneal epithelial disease except mild punctuate keratopathy.
• Contact lenses are not allowed for participants while they are receiving belantamab mafodotin treatment.
• Patients must not have symptomatic amyloidosis or active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma-proliferative disorder, skin changes) at the time of screening.
• Patients must not receive any other concurrent chemotherapy, or any ancillary therapy considered investigational while on this protocol.

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

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

PrECOG, LLC.

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shaji Kumar, MD

Role: STUDY_CHAIR

Mayo Clinic

Central Contacts

Michael Wright, MS

Role: CONTACT

PrE1005@precogllc.org

267-319-3910

Other Identifiers

GSK 300057

Identifier Type: OTHER

Identifier Source: secondary_id

PrE1005

Identifier Type: -

Identifier Source: org_study_id