Study of Alternative and Approved Dosing Regimens of Belantamab Mafodotin, Bortezomib, and Dexamethasone (BVd) in Participants With Relapsed/Refractory Multiple Myeloma (DREAMM-16)

A Phase 2, Multicenter, Randomized, Open-label Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Alternative and Approved Dosing Regimens of Belantamab Mafodotin in Combination With Bortezomib and Dexamethasone (BVd) in Participants With Relapsed/Refractory Multiple Myeloma

The aim of this study is to assess safety, efficacy and pharmacokinetic (PK) parameters with alternative dosing schedules of belantamab mafodotin in combination with bortezomib and dexamethasone compared to the approved dosing regimen in participants with relapsed or refractory multiple myeloma (RRMM) who have received at least 2 prior lines of therapy. The study will further characterize the risk of ocular toxicity and impact on efficacy measures and PK evaluations using alternative and approved dosing regimens.

Study Overview

• Status: Not yet recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Belantamab mafodotin; Drug: Dexamethasone; Drug: Bortezomib

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

• Study Contact: Name: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
• Study Contact Backup: Name: EU GSK Clinical Trials Call Center; Phone Number: +44 (0) 20 89904466; Email: GSKClinicalSupportHD@gsk.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Is at least 18 years of age or the legal age of consent in the jurisdiction in which the study is taking place at the time of signing the Informed consent form (ICF).
• Has histologically or cytologically confirmed diagnosis of Multiple myeloma (MM), as defined by the IMWG.
• Previously treated with at least 2 prior lines of MM therapy, including a proteasome inhibitor and an immunomodulatory agent.

• Has at least 1 aspect of measurable disease, as assessed by the central laboratory, defined as at least 1 of the following:

  • Urine M-protein excretion >=200 milligrams (mg)/24 hours (>=0.2 grams [g]/24 hours)
  • Serum M-protein concentration >=0.5 grams per deciliter (g/dL) (>=5.0 g/L)
  • Serum free light chain (FLC) assay: involved FLC level >=10 milligrams per deciliter (mg/dL) (>=100 mg/L) and an abnormal serum FLC ratio (less than [<] 0.26 or greater than [>] 1.65).

• Participants with a history of autologous stem cell transplants are eligible for study participation provided the following eligibility criteria are met:

  • Transplant was > 100 days prior to study enrollment
  • No active infection(s)
  • Participant meets the remainder of the eligibility criteria
• All prior treatment-related toxicities (defined by NCI-CTCAE version [v] 6.0) must be Grade less than or equal to (<=)1 at the time of treatment assignment, except for alopecia (any grade), neuropathy (Grade <=2), or endocrinopathy managed with replacement therapy (any grade).

• Is willing to use adequate contraception male and female participants. Contraceptive use by male and female participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

  1. 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 belantamab mafodotin and 5 months after the last dose of bortezomib, whichever is longest, 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 usual lifestyle (abstinent on a long-term and persistent basis), including any activity or passage of ejaculate to another person, and agree to remain abstinent. 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 method with a failure rate of <1 percent (%) per year when having sexual intercourse with a partner who can become pregnant and is not currently pregnant. Male participants should also use a condom when having sexual intercourse with pregnant females

  2. Female participants are eligible to participate if they are not pregnant or breastfeeding, and one of the following conditions applies:

     • Is a Person of non-childbearing potential (PONCBP) OR
     • Is a Person of childbearing potential (POCBP) and using a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency, during the study intervention period and for at 4 months after the last dose of belantamab mafodotin or 8 months after the last dose of bortezomib, whichever is longest, and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of study intervention.
     • A POCBP must have a negative highly sensitive serum pregnancy tests within 72 hours before the first dose of study intervention.
     • The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a person with an early undetected pregnancy.
• Is capable of giving signed informed consent.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Has adequate organ system functions as defined by the laboratory assessments.
• Participants with a history of Hepatitis B virus (HBV) and/or Hepatitis C virus (HCV) and Human immunodeficiency virus (HIV) exposure are eligible under specific conditions.

Exclusion Criteria:

• Intolerant to bortezomib
• Diagnosis of systemic amyloid light chain amyloidosis, Waldenstrom's disease, polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, skin changes (POEMS) or Primary Plasma Cell Leukemia (defined as circulating plasma cells >5%)
• Has previous or concurrent invasive malignancy other than Multiple myeloma (MM), except:

The disease must be considered medically stable for at least 2 years; or

• The participant must not be receiving active therapy, other than hormonal therapy for this disease.

  • Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to belantamab mafodotin or drugs chemically related to belantamab mafodotin, or any of the components of the study treatment.
  • Evidence of active mucosal or internal bleeding.
  • Active infection requiring treatment
  • Any major surgery within 4 weeks prior to the first dose of study drug. Exception allowed for bone stabilizing surgery after consultation with Medical Monitor.
  • Active or history of venous and arterial thromboembolism within the past 3 months.
  • Contraindications to or unwilling to undergo protocol-required anti-thrombotic prophylaxis.
  • Current corneal epithelial disease except for mild punctate keratopathy
  • Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions (including laboratory abnormalities) that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures.
  • Participants after prior allogeneic stem cell transplant.
  • Has received prior belantamab mafodotin therapy.
  • Has received treatment with an investigational agent within 14 days or 5 half-lives, whichever is shorter, preceding the first dose of study drug. This includes prior treatment with a monoclonal antibody and any other B-cell maturation antigen (BCMA) targeting-therapy. The only exception is emergency use of a short course of systemic corticosteroids (equivalent to, or less than: dexamethasone 40 mg/day for a maximum of 4 days) before treatment.
  • Systemic anti-myeloma therapy (including chemotherapy and systemic steroids); prior treatment with an anti-MM monoclonal antibody drug within 30 days of receiving the first dose of study intervention.
  • Plasmapheresis within 7 days prior to the first dose of study treatment. Screening laboratory values must be performed after last plasmapheresis
  • Has received any live vaccine within 30 days of randomization/enrollment. Vaccination against Coronavirus Disease 2019 (COVID-19) using vaccines that are authorized via the appropriate regulatory mechanisms (e.g., Emergency Use Authorization, Conditional Marketing Authorization, or Marketing Authorization Application) are not exclusionary.
  • Is currently enrolled or has participated in any other clinical study involving an investigational drug within 14 days or 5 half-lives (whichever is shorter) preceding the first dose of study intervention.
  • Known Human immunodeficiency virus (HIV) infection, unless the participant can meet all of the following criteria:
• Established anti-retroviral therapy for at least 4 weeks and HIV viral; load <400 copies/milliliter (mL)
• Cluster of differentiation 4 (CD4+) T-cell counts >=350 cells/microliter;

• No history of acquired immune deficiency syndrome (AIDS)-defining opportunistic infections within the last 12 months.

  • Is pregnant, plan to become pregnant, or breastfeeding.
  • Has an Alanine aminotransferase (ALT) value >2.5 times Upper limit of normal (ULN).
  • Has a total bilirubin value >1.5 times ULN
  • Has cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice.
  • Has a positive Hepatitis C virus (HCV) antibody test result at screening or within 3 months prior to the first dose of study intervention unless HCV Ribonucleic acid (RNA) is negative, indicating past resolved HCV infection, including participants who have undergone curative treatment.
  • Has a positive HCV RNA test result at screening or within 3 months prior to the first dose of study intervention.
  • Has documented presence of Hepatitis B surface antigen (HBsAg) and/or Hepatitis B virus antibody (HBcAb) at screening or within 3 months prior to the first dose of study intervention unless specific criteria are met.
  • Evidence of cardiovascular risk including any of the following:
• Evidence of current clinically significant untreated arrhythmias, including clinically significant electrocardiogram (ECG) abnormalities including second degree (Mobitz Type II) or third degree atrioventricular block.
• History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 3 months of Screening
• Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
• Uncontrolled hypertension • Has QT interval corrected (QTc) >450 milliseconds (msec) or QTc >480 msec for participants with bundle branch block.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Participants receiving Belantamab mafodotin dosing regimen 1 + Bortezomib + Dexamethasone; Participants will receive dosing regimen 1 of Belantamab mafodotin in combination with Bortezomib and Dexamethasone	Drug: Belantamab mafodotin; Belantamab mafodotin will be administered; Drug: Dexamethasone; Dexamethasone will be administered.; Drug: Bortezomib; Bortezomib will be administered
Experimental: Participants receiving Belantamab mafodotin dosing regimen 2 + Bortezomib + Dexamethasone; Participants will receive dosing regimen 2 of Belantamab mafodotin in combination with Bortezomib and Dexamethasone.	Drug: Belantamab mafodotin; Belantamab mafodotin will be administered; Drug: Dexamethasone; Dexamethasone will be administered.; Drug: Bortezomib; Bortezomib will be administered
Experimental: Participants receiving Belantamab mafodotin dosing regimen 3 + Bortezomib + Dexamethasone; Participants will receive dosing regimen 3 of Belantamab mafodotin in combination with Bortezomib and Dexamethasone.	Drug: Belantamab mafodotin; Belantamab mafodotin will be administered; Drug: Dexamethasone; Dexamethasone will be administered.; Drug: Bortezomib; Bortezomib will be administered

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants with grade greater than or equal to (>=)3 corneal events assessed by keratopathy visual acuity (KVA) scale	KVA scale ranges from 0 to 4 with higher score indicating greater severity of corneal events.	Up to approximately 4.5 years
Percentage of participants with grade >=3 corneal events assessed by KVA scale up to Month 6	KVA scale ranges from 0 to 4 with higher score indicating greater severity of corneal events.	Up to Month 6
Percentage of Participants With Grade >=3 Corneal Events Assessed by KVA scale from 6 to 12 months	KVA scale ranges from 0 to 4 with higher score indicating greater severity of corneal events. Data will be presented for the total number of participants with corneal events in each study group during 6 to 12 months.	From 6 to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of corneal events as assessed by KVA scale accounting for time on study treatment	KVA scale ranges from 0 to 4 with higher scores indicating greater severity of corneal events.	Up to approximately 4.5 years
Percentage of participants with corneal events as assessed by KVA scale	KVA scale ranges from 0 to 4 with higher scores indicating greater severity of corneal events.	Up to approximately 4.5 years
Number of recurrences of corneal events as assessed by KVA scale	Number of recurrences of corneal events is defined as the total count of individual corneal event occurrences per participant over the study period. KVA scale ranges from 0 to 4 with higher scores indicating greater severity of corneal events.	Up to approximately 4.5 years
Percentage of participants with post-baseline Best corrected visual acuity of 20/50, 20/100, 20/200	Best corrected visual acuity test results are expressed as a fraction, such as 20/50. The top number is the testing distance of 20 feet, and the bottom number is the distance at which a person with average vision could read the same line. 20/50 indicates mild visual impairment, 20/100 indicates moderate visual impairment and 20/200 indicates severe visual impairment.	Up to approximately 4.5 years
Number of participants with ocular adverse events and adverse events of special interest by National Cancer Institute-Common terminology criteria for adverse events (NCI-CTCAE) Version 6.0		Up to approximately 4.5 years
Number of participants with adverse events related dose modifications due to ocular toxicity by NCI-CTCAE Version 6.0		Up to approximately 4.5 years
Number of participants with adverse events related dose modifications due to ocular toxicity by KVA scale	KVA scale ranges from 0 to 4 with higher scores indicating greater severity of corneal events.	Up to approximately 4.5 years
Overall Response Rate (ORR)	ORR is defined as the percentage of participants with a confirmed partial response (PR) or better as assessed by the investigator per International Myeloma Working Group (IMWG) criteria.	Up to approximately 4.5 years
Percentage of participants with a confirmed Very good partial response (VGPR) or better		Up to approximately 4.5 years
Minimal Residual Disease (MRD) Negativity Rate	MRD negativity rate, defined as the percentage of participants who are MRD-negative by next-generation sequencing (NGS) at 10^-5 sensitivity threshold during the time of confirmed complete response (CR) or better response as assessed by the investigator per IMWG criteria.	Up to approximately 4.5 years
Progression-Free Survival (PFS)	PFS is defined as the time from randomization until the earliest date of documented Progressive disease (PD) as assessed by the investigator per IMWG criteria or death due to any cause.	Up to approximately 4.5 years
Number of participants with adverse events by NCI-CTCAE Version 6.0		Up to approximately 4.5 years
Number of participants with clinically significant changes in hematology, chemistry, urinalysis parameters		Up to approximately 4.5 years
Concentration at end of infusion (C-EOI) following administration of belantamab mafodotin		Up to approximately 4.5 years
Area under the plasma concentration-time curve from time 0 to time t (AUC[0-t]) following administration of belantamab mafodotin		Up to approximately 4.5 years
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of life questionnaire core 30 (EORTC QLQ-C30) score	The EORTC QLQ-C30 score ranges from 0 to 100 with higher score indicates better functioning or a better overall state of health.	Baseline (Day 1) and up to approximately 4.5 years
Maximum Post-baseline Patient-reported Outcome Common Terminology Criteria for Adverse Events (PRO-CTCAE) Scores	The PRO-CTCAE is a patient-reported outcome measure developed to evaluate symptomatic toxicities in participants in cancer clinical trials and is measured using a scale ranging from 0 to 100. Higher scores indicate poorer side effect experiences.	Up to approximately 4.5 years
Mean change from Baseline in vision-related functioning as measured by ocular surface disease index (OSDI)	The OSDI scores range from 0 to 100. Higher score indicates greater symptom severity.	Baseline (Day 1) and up to approximately 4.5 years

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Estimated): August 3, 2026
• Primary Completion (Estimated): February 28, 2029
• Study Completion (Estimated): February 11, 2031

Study Registration Dates

• First Submitted: May 21, 2026
• First Submitted That Met QC Criteria: May 21, 2026
• First Posted (Actual): May 29, 2026

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Dexamethasone; Bortezomib; Proteasome inhibitor; Immunomodulatory agent; Belantamab mafodotin; Corneal events; DREAMM-16
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds; Inorganic Chemicals; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Pregnadienetriols; Boronic Acids; Acids, Noncarboxylic; Acids; Boron Compounds; Pyrazines; Bortezomib; Dexamethasone; belantamab mafodotin
• Other Study ID Numbers: 300948; 2026-526724-43 (Registry Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No