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

NCT07285239 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: PrE1005GSK 300057
• Study Type: interventional
• Target: 500
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Multiple Myeloma

Keywords

Newly Diagnosed High-Risk Multiple Myeloma; Transplant Ineligible Multiple Myeloma; High-Risk Cytogenetic Multiple Myeloma; Belantamab Mafodotin; Daratumumab-Hyaluronidase; Daratumumab; Bortezomib; Lenalidomide; Decadron; Dexamethasone

Outcome Measures

Primary Outcomes (2)

• MRD Negative Status in All-Comers

  MRD negative status, defined as achieving MRD negativity at 10\^-5 sensitivity threshold assessed by next-generation sequencing (NGS) in patients achieving CR or better after 12 (+/- 3) months of treatment; MRD negativity is determined by the Adaptive Biotechnologies clonoSEQ® assay result; All-comers: the initial cohort of 400 consecutively enrolled patients, irrespective of IMS-IMWG risk status.

  9 to 15 months

• Progression-Free Survival (PFS) in High-Risk Cytogenetics Enriched Cohort

  PFS, defined as the time from the date of randomization to the date of first documented disease progression per IMWG criteria or death from any cause in the absence of progression, whichever occurs first; High-risk cytogenetics enriched cohort: includes the 400 all-comers and 100 additional patients with high-risk cytogenetics.

  Up to 7 years

Secondary Outcomes (11)

• PFS in High-Risk Cytogenetics Cohort

  Up to 7 years

• Overall Survival (OS)

  Up to 7 years

• Best Response of Complete Response (CR)

  Up to 7 years

• Best Response of Very Good Partial Response (VGPR)

  Up to 7 years

• Duration of Response (DoR)

  Up to 7 years

Study Arms (2)

Arm A: Belantamab Mafodotin

EXPERIMENTAL

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

Drug: Arm A: Belantamab Mafodotin; Drug: Bortezomib; Drug: Lenalidomide; Drug: Dexamethasone

Arm B:

ACTIVE COMPARATOR

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

Drug: Arm B: Daratumumab Hyaluronidase; Drug: Bortezomib; Drug: Lenalidomide; Drug: Dexamethasone

Interventions

Arm A: Belantamab Mafodotin 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

Also known as: GSK2857916, Blenrep, Belamaf

Arm A: Belantamab Mafodotin

Arm B: Daratumumab Hyaluronidase 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

Also known as: DARZALEX FASPRO™

Arm B:

Bortezomib 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

Also known as: Velcade®

Arm A: Belantamab Mafodotin; Arm B:

Lenalidomide DRUG

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

Also known as: Revlimid®

Arm A: Belantamab Mafodotin; Arm B:

Dexamethasone DRUG

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

Also known as: Decadron

Arm A: Belantamab Mafodotin; Arm B:

Eligibility Criteria

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

Eligibility Criteria: * Patient must have suspected or confirmed newly diagnosed multiple myeloma (MM) by International Myeloma Working Group (IMWG) criteria and must not have received more than one cycle of any myeloma treatment. * Patient must be considered ineligible for autologous stem cell transplantation by the treating physician, or willing to delay stem cell transplantation until first relapse or later. * 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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• PrECOG, LLC.: lead
• GlaxoSmithKline: collaborator

MeSH Terms

Conditions

Multiple Myeloma

Interventions

belantamab mafodotin; Bortezomib; Lenalidomide; Dexamethasone; Calcium Dobesilate

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)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Shaji Kumar, MD

  Mayo Clinic

  STUDY CHAIR

Central Study Contacts

Michael Wright, MS

CONTACT

267-319-3910; PrE1005@precogllc.org

Study Design

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

Model Details: Open-label, randomized (1:1) to either belantamab mafodotin or daratumumab given in combination with bortezomib, lenalidomide and dexamethasone (VRd) until progression. Participants will be stratified by IMWG risk criteria and intention to transplant at disease progression.

Study Record Dates

• First Submitted: December 9, 2025
• First Posted: December 16, 2025
• Study Start: May 1, 2026
• Primary Completion (Estimated): September 1, 2031
• Study Completion (Estimated): April 1, 2034
• Last Updated: December 16, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share