Study to Investigate Alternative Dosing Regimens of Belantamab Mafodotin in Participants With Relapsed or Refractory Multiple Myeloma

Study Overview
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Brief Summary
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This study aims to evaluate alternative dosing regimens of single-agent belantamab mafodotin in participants with relapsed or refractory multiple myeloma (RRMM) to determine if an improved overall benefit/risk profile can be achieved by modifying the belantamab mafodotin dose, schedule, or both.

Official Title
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A Phase 2, Randomized, Parallel, Open-label Study to Investigate the Safety, Efficacy, and Pharmacokinetics of Various Dosing Regimens of Single-agent Belantamab Mafodotin (GSK2857916) in Participants With Relapsed or Refractory Multiple Myeloma (DREAMM-14)

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Belantamab mafodotin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must be 18 years of age inclusive at the time of signing the informed consent form (ICF). Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. Histologically or cytologically confirmed diagnosis of MM and a. Has undergone stem cell transplant or is considered transplant ineligible, and b. Has failed at least 3 prior lines of anti-myeloma therapies, including an anti-cluster of differentiation (CD)38 antibody (e.g., daratumumab) alone or in combination and is refractory to an immunomodulatory agent (e.g., lenalidomide, pomalidomide) and a proteasome inhibitor (e.g., bortezomib, ixazomib, carfilzomib). France specific: participants have failed at least 4 prior lines of anti-myeloma therapies Participant has measurable disease per modified IMWG criteria. Life expectancy of at least 6 months, in the opinion of the investigator. Male and female participants agree to abide by protocol-defined contraceptive requirements. Participant is capable of giving signed informed consent. Participant meets country-specific inclusion criteria described in the protocol. Exclusion Criteria: Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes), or active plasma cell leukemia at the time of screening. Current corneal epithelial disease, except nonconfluent superficial punctate keratitis (SPK). Evidence of active mucosal or internal bleeding. Presence of an active renal condition. Any serious and/or unstable pre-existing medical condition, psychiatric disorder, or other conditions that could interfere with the participant's safety, obtaining informed consent, or compliance with the study procedures. Malignancies other than the disease under study, except for any other malignancy from which the participant has been disease free for >2 years and, will not affect the evaluation of the effects of the study treatment on the currently targeted malignancy (MM). Participants with curatively treated non-melanoma skin cancer may be enrolled without a 2-year restriction. Evidence of cardiovascular risk as per the protocol criteria. Pregnant or lactating female. Active infection requiring antibiotic, antiviral, or antifungal treatment. Known human immunodeficiency virus (HIV) infection, unless the criteria in protocol can be met. Hepatitis B and C will be excluded unless the criteria in protocol can be met. Cirrhosis or current unstable liver or biliary disease. Alanine aminotransferase (ALT) >2.5× upper limit of normal (ULN). Total Bilirubin >1.5×ULN. Systemic anti-MM therapy within <=14 days or 5 half-lives, whichever is shorter. Systemic therapy with high dose steroids within <=14 days before the first dose of study treatment. Prior allogenic stem cell transplant. Prior treatment with a monoclonal antibody <=30 days before the first dose of study treatment. Use of monoclonal antibodies for serious conditions unrelated to multiple myeloma, such as COVID, may be permitted. Prior treatment with an anti-B cell maturation antigen (BCMA) targeted therapy or hypersensitivity reactions to any components of the study treatment. Treatment with an antibody-drug conjugate. Participant has received any major surgery <=4 weeks before the first dose of study treatment. An exception may be allowed for bone stabilizing surgery. Inadequate bone marrow reserve or organ functions as demonstrated by any of the following: a. Absolute neutrophil count <1.0×10^9/L, b. Hemoglobin <8 gram/deciliter (g/dL), c. Platelet count <50×10^9/L, d. Spot urine (albumin/creatinine ratio) >500 milligram/gram (mg/g), e. Estimated glomerular filtration rate (eGFR) <30 milliliter per minute per 1.73 meter square (mL/min/1.73m^2). UK specific: a. Absolute neutrophil count <1.5×10^9/L, c. Platelet count <75×10^9/L

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Belantamab mafodotin will be administered using various dosing regimens.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: Participants receiving belantamab mafodotin at dose level (DL) 1<br> | Drug: Belantamab mafodotin<br>* Belantamab mafodotin will be administered.<br>|
| Experimental: Cohort 2: Participants receiving belantamab mafodotin at DL 2<br> | Drug: Belantamab mafodotin<br>* Belantamab mafodotin will be administered.<br>|
| Experimental: Cohort 3: Participants receiving belantamab mafodotin at DL 3<br> | Drug: Belantamab mafodotin<br>* Belantamab mafodotin will be administered.<br>|
| Experimental: Cohort 4: Participants receiving belantamab mafodotin at DL 4<br> | Drug: Belantamab mafodotin<br>* Belantamab mafodotin will be administered.<br>|
| Experimental: Cohort 5: Participants receiving belantamab mafodotin at DL4 with alternative dose modification<br> | Drug: Belantamab mafodotin<br>* Belantamab mafodotin will be administered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rate of Grade ≥2 Corneal events according to the keratopathy visual acuity (KVA) scale | KVA scale is used to grade the corneal events from Grade 0-4. KVA grading is a composite score considering corneal exam findings (ranging from clear cornea [Grade 0] to corneal ulcer [Grade 4]), as well as changes in visual acuity (ranging from no change from Baseline in visual acuity [Grade 0] to visual acuity worse than 1.0 logarithm of the minimum angle of resolution ([logMAR] (20/200) [Grade 4]). The KVA grade is driven by the most severe finding. | Up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative event rate of corneal events to Week 16 (KVA scale) |  | Up to Week 16 | 
| Incidence rate of corneal events by grade (KVA scale) | KVA scale is used to grade the corneal events from Grade 0-4. KVA grading is a composite score considering corneal exam findings (ranging from clear cornea [Grade 0] to corneal ulcer [Grade 4]), as well as changes in visual acuity (ranging from no change from Baseline in visual acuity [Grade 0] to visual acuity worse than 1.0 logMAR (20/200) [Grade 4]). The KVA grade is driven by the most severe finding. | Up to 12 months | 
| Exposure adjusted incidence rate of corneal events by grade (KVA scale) | The exposure adjusted incidence rate is defined as the number of participants with corneal events divided by the total exposure in subject years among participants in the respective treatment group at risk of an initial occurrence of the event. | Up to 12 months | 
| Median duration of dose delay | Median duration of dose delay is defined as the median duration in time of all the dose delays in the respective treatment group. | Up to 12 months | 
| Percentage of participants requiring dose reductions, dose delays, and study treatment discontinuation due to corneal events |  | Up to 12 months | 
| Cumulative incidence of corneal events by grade | Cumulative incidence of corneal events by grade is calculated using the KVA scale, as the number of new events divided by the total number of individuals in the population at risk for a specific time interval. | Up to 12 months | 
| Toxicity Index score by assessment/visit | Toxicity Index score is defined as a function of the ordered toxicity grades, where the toxicity grades are represented in descending order by the sequence. | Up to 12 months | 
| Duration of corneal events | Duration of corneal events is defined as the sum of the duration of all the corneal events of a participant. | Up to 12 months | 
| Percentage of time on study with corneal events | Percentage of time on study with corneal events is defined as the duration of corneal events divided by the total amount of time that a participant is on the study in percentage. | Up to 12 months | 
| Change in best corrected visual acuity (BCVA) | BCVA will be assessed as per Snellen (or Snellen-equivalent) chart. | Up to 12 months | 
| Overall response rate (ORR) | Percentage of participants with a confirmed partial response (PR) or better per International Myeloma Working Group (IMWG) criteria. | Up to 12 months | 
| Percentage of participants with very good partial response (VGPR) or better |  | Up to 12 months | 
| Time to response (TTR) | Time between the date of randomization and the first documented evidence of response (PR or better) among participants who achieve confirmed PR or better. | Up to 12 months | 
| Duration of response (DoR) | Time from first documented evidence of PR or better until progressive disease (PD) per IMWG or death due to any cause. | Up to 12 months | 
| Time to progression (TTP) | Time from the date of randomization until the earliest date of documented PD (per IMWG Response Criteria) or death due to PD. | Up to 12 months | 
| Progression-free survival (PFS) | Time from the date of randomization until the earliest date of documented PD (according to IMWG Response Criteria) or death due to any cause. | Up to 12 months | 
| Overall survival (OS) | Time from the date of randomization until death due to any cause. | Up to 12 months | 
| Number of participants with AEs and serious AEs (SAEs) |  | Up to 12 months | 
| Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis laboratory parameters |  | Up to 12 months | 
| Percentage of participants requiring dose reductions, dose delays, and study treatment discontinuation due to any AEs |  | Up to 12 months | 
| Maximum concentration (Cmax) of belantamab mafodotin |  | Up to 12 months | 
| Time taken to reach Cmax (Tmax) of belantamab mafodotin |  | Up to 12 months | 
| Area under the concentration time-curve (AUC) of belantamab mafodotin |  | Up to 12 months | 
| Number of participants with positive anti-drug antibodies (ADAs) against belantamab mafodotin |  | Up to 12 months | 
| Titers of ADAs against belantamab mafodotin |  | Up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antibody drug conjugate, Belantamab mafodotin, BLENREP, DREAMM14, GSK2857916, Alternative dosing, Relapsed or refractory multiple myeloma, RRMM