NCT07285239

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

Randomized Phase 3 Trial of Belantamab Mafodotin or Daratumumab in Combination With Bortezomib, Lenalidomide and Dexamethasone for Newly Diagnosed Multiple Myeloma

• Status: Not Yet Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 500 (estimated)
• Sponsor: PrECOG, LLC. · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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

Interventions

Type	Name	Description
DRUG	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
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
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
DRUG	Lenalidomide	25 mg orally (PO) Days 1-21 of every 28 day lenalidomide treatment cycle.
DRUG	Dexamethasone	40 mg PO on Days 1, 8, 15, and 22 of each 28-day cycle

Timeline

• Start date: 2026-05-01
• Primary completion: 2031-09-01
• Completion: 2034-04-01
• First posted: 2025-12-16
• Last updated: 2025-12-16

Regulatory

• FDA-regulated drug study