Study to Investigate Alternative Dosing Regimens of Belantamab Mafodotin in Participants With Relapsed or Refractory Multiple Myeloma (DREAMM 14)

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Belantamab mafodotin

• Study Type: Interventional
• Enrollment (Anticipated): 180
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Autonoma de Buenos Aires, Argentina, 1414
    • Recruiting
    • GSK Investigational Site
  • Ciudad Autonoma de Buenos Aires, Argentina, C1181ACH
    • Recruiting
    • GSK Investigational Site
  • Buenos Aires
    • Capital Federal, Buenos Aires, Argentina, C1426ANZ
      • Recruiting
      • GSK Investigational Site
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2002
      • Recruiting
      • GSK Investigational Site
• Australia
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
      • Recruiting
      • GSK Investigational Site
    • Waratah, New South Wales, Australia, 2298
      • Recruiting
      • GSK Investigational Site
  • South Australia
    • Woodville, South Australia, Australia, 5011
      • Recruiting
      • GSK Investigational Site
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
      • Recruiting
      • GSK Investigational Site
• Brazil
  • Rio de Janeiro, Brazil, 22271-110
    • Recruiting
    • GSK Investigational Site
  • São Paulo, Brazil, 01236-030
    • Recruiting
    • GSK Investigational Site
  • São Paulo, Brazil, 04537-080
    • Recruiting
    • GSK Investigational Site
    • Principal Investigator: Vania Tietsche Hungria
  • Bahía
    • Salvador, Bahía, Brazil, 41253-190
      • Recruiting
      • GSK Investigational Site
  • Paraná
    • Curitiba, Paraná, Brazil, 80040-170
      • Recruiting
      • GSK Investigational Site
      • Principal Investigator: Johnny Francisco Camargo
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90850-170
      • Recruiting
      • GSK Investigational Site
      • Principal Investigator: Marcelo Eduardo Capra
  • Santa Catarina
    • Joinville, Santa Catarina, Brazil, 89201-260
      • Recruiting
      • GSK Investigational Site
• Canada
  • Ontario
    • Oshawa, Ontario, Canada, L1G 2B9
      • Recruiting
      • GSK Investigational Site
    • Toronto, Ontario, Canada, M5G 2M9
      • Recruiting
      • GSK Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
      • Recruiting
      • GSK Investigational Site
    • Montréal, Quebec, Canada, H4J 1C5
      • Recruiting
      • GSK Investigational Site
• France
  • Avignon cedex 9, France, 84902
    • Recruiting
    • GSK Investigational Site
  • Le Mans, France, 72000
    • Recruiting
    • GSK Investigational Site
  • Nice Cedex 2, France, 06189
    • Recruiting
    • GSK Investigational Site
  • Orléans, France, 45100
    • Recruiting
    • GSK Investigational Site
  • Saint-Priest en Jarez, France, 42270
    • Recruiting
    • GSK Investigational Site
• Germany
  • Hamburg, Germany, 22763
    • Recruiting
    • GSK Investigational Site
  • Baden-Wuerttemberg
    • Karlsruhe, Baden-Wuerttemberg, Germany, 76133
      • Recruiting
      • GSK Investigational Site
  • Brandenburg
    • Cottbus, Brandenburg, Germany, 03048
      • Recruiting
      • GSK Investigational Site
  • Mecklenburg-Vorpommern
    • Greifswald, Mecklenburg-Vorpommern, Germany, 17475
      • Recruiting
      • GSK Investigational Site
  • Niedersachsen
    • Oldenburg, Niedersachsen, Germany, 26133
      • Recruiting
      • GSK Investigational Site
  • Nordrhein-Westfalen
    • Dortmund, Nordrhein-Westfalen, Germany, 44137
      • Recruiting
      • GSK Investigational Site
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • Recruiting
      • GSK Investigational Site
• Greece
  • Athens, Greece, 11528
    • Recruiting
    • GSK Investigational Site
  • Athens, Greece, 106 76
    • Recruiting
    • GSK Investigational Site
  • Haidari, Athens, Greece, 12462
    • Recruiting
    • GSK Investigational Site
  • Rio/Patras, Greece, 26504
    • Recruiting
    • GSK Investigational Site
  • Thessaloniki, Greece, 57010
    • Recruiting
    • GSK Investigational Site
• India
  • Ahmedabad, India, 380009
    • Recruiting
    • GSK Investigational Site
  • Bangalore, India, 560054
    • Recruiting
    • GSK Investigational Site
  • Hyderabad, India, 500033
    • Recruiting
    • GSK Investigational Site
  • Kerala, India, 682041
    • Recruiting
    • GSK Investigational Site
  • Kolkata, India, 700014
    • Recruiting
    • GSK Investigational Site
  • Kolkata, India, 700156
    • Recruiting
    • GSK Investigational Site
  • Mumbai, India, 400071
    • Recruiting
    • GSK Investigational Site
  • Pondicherry, India, 605006
    • Recruiting
    • GSK Investigational Site
  • Pune, India, 411004
    • Recruiting
    • GSK Investigational Site
  • Maharashtra
    • Nashik, Maharashtra, India, 422005
      • Recruiting
      • GSK Investigational Site
• Ireland
  • Dublin, Ireland, 8
    • Recruiting
    • GSK Investigational Site
  • Dublin, Ireland, D09 V2N0
    • Recruiting
    • GSK Investigational Site
• Italy
  • Cagliari, Italy, 09121
    • Recruiting
    • GSK Investigational Site
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • Recruiting
      • GSK Investigational Site
    • Cona (FE), Emilia-Romagna, Italy, 44124
      • Recruiting
      • GSK Investigational Site
    • Meldola, Emilia-Romagna, Italy, 47014
      • Recruiting
      • GSK Investigational Site
    • Reggio Emilia, Emilia-Romagna, Italy, 42123
      • Recruiting
      • GSK Investigational Site
    • Rimini, Emilia-Romagna, Italy, 47900
      • Recruiting
      • GSK Investigational Site
  • Liguria
    • Genova, Liguria, Italy, 16132
      • Recruiting
      • GSK Investigational Site
  • Marche
    • Ascoli Piceno, Marche, Italy, 63100
      • Recruiting
      • GSK Investigational Site
  • Piemonte
    • Alessandria, Piemonte, Italy, 15121
      • Recruiting
      • GSK Investigational Site
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Recruiting
    • GSK Investigational Site
  • Hwasun-gun, Jeollanam-do, Korea, Republic of, 58128
    • Recruiting
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 06591
    • Recruiting
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • GSK Investigational Site
• Mexico
  • Ciudad De Mexico
    • Mexico, Ciudad De Mexico, Mexico, 03100
      • Recruiting
      • GSK Investigational Site
    • Mexico City, Ciudad De Mexico, Mexico, 03720
      • Recruiting
      • GSK Investigational Site
• Poland
  • Bydgoszcz, Poland, 85-168
    • Recruiting
    • GSK Investigational Site
  • Gdansk, Poland, 80-214
    • Recruiting
    • GSK Investigational Site
  • Katowice, Poland, 40-519
    • Recruiting
    • GSK Investigational Site
  • Lublin, Poland, 20-081
    • Recruiting
    • GSK Investigational Site
  • Nowy Sacz, Poland, 33-300
    • Recruiting
    • GSK Investigational Site
  • Walbrzych, Poland, 58-309
    • Recruiting
    • GSK Investigational Site
  • Warszawa, Poland, 02-781
    • Recruiting
    • GSK Investigational Site
  • Wroclaw, Poland, 50-367
    • Recruiting
    • GSK Investigational Site
• Spain
  • Albacete, Spain, 02006
    • Recruiting
    • GSK Investigational Site
  • Alcorcón (Madrid), Spain, 28922
    • Recruiting
    • GSK Investigational Site
  • Barcelona, Spain, 08026
    • Recruiting
    • GSK Investigational Site
  • Cordoba, Spain, 140044
    • Recruiting
    • GSK Investigational Site
  • Gerona, Spain, 17007
    • Recruiting
    • GSK Investigational Site
  • Lleida, Spain, 25198
    • Recruiting
    • GSK Investigational Site
  • Terrassa (Barcelona), Spain, 08221
    • Recruiting
    • GSK Investigational Site
  • Valencia, Spain, 46010
    • Recruiting
    • GSK Investigational Site
  • Asturias
    • Oviedo, Asturias, Spain, 33011
      • Recruiting
      • GSK Investigational Site
• Switzerland
  • Bern, Switzerland, 3010
    • Recruiting
    • GSK Investigational Site
• Taiwan
  • Taichung, Taiwan, 404
    • Recruiting
    • GSK Investigational Site
  • Taichung, Taiwan, 40705
    • Recruiting
    • GSK Investigational Site
  • Tainan, Taiwan, 704
    • Recruiting
    • GSK Investigational Site
  • Taipei, Taiwan, 100
    • Recruiting
    • GSK Investigational Site
  • Taipei, Taiwan, 112
    • Recruiting
    • GSK Investigational Site
• Thailand
  • Bangkok, Thailand, 10210
    • Recruiting
    • GSK Investigational Site
  • Bangkok, Thailand, 10330
    • Recruiting
    • GSK Investigational Site
  • Chiang Mai, Thailand, 50200
    • Recruiting
    • GSK Investigational Site
  • Khon Kaen, Thailand, 40002
    • Recruiting
    • GSK Investigational Site
• United Kingdom
  • Leicester, United Kingdom, LE1 5WW
    • Recruiting
    • GSK Investigational Site
  • London, United Kingdom, SW17 0QT
    • Recruiting
    • GSK Investigational Site
  • London, United Kingdom, W12 0HS
    • Recruiting
    • GSK Investigational Site
  • Staffordshire
    • Stoke-on-Trent, Staffordshire, United Kingdom, ST4 6QG
      • Recruiting
      • GSK Investigational Site
• United States
  • Florida
    • New Port Richey, Florida, United States, 34655
      • Recruiting
      • GSK Investigational Site
    • West Palm Beach, Florida, United States, 33401
      • Recruiting
      • GSK Investigational Site
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • Recruiting
      • GSK Investigational Site
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • GSK Investigational Site
      • Principal Investigator: Malin Hultcrantz
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Recruiting
      • GSK Investigational Site
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • GSK Investigational Site
  • Texas
    • Houston, Texas, United States, 77090
      • Recruiting
      • GSK Investigational Site
      • Principal Investigator: Woondong Jeong
  • Washington
    • Spokane, Washington, United States, 99218
      • Recruiting
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

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

5

Arms and Interventions

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

What is the study measuring?

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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2022
• Primary Completion (Anticipated): May 13, 2024
• Study Completion (Anticipated): September 6, 2024

Study Registration Dates

• First Submitted: September 22, 2021
• First Submitted That Met QC Criteria: September 22, 2021
• First Posted (Actual): October 1, 2021

Study Record Updates

• Last Update Posted (Actual): April 12, 2023
• Last Update Submitted That Met QC Criteria: April 10, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: RRMM; Antibody drug conjugate; Relapsed or refractory multiple myeloma; Belantamab mafodotin; BLENREP; DREAMM14; GSK2857916; Alternative dosing
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: 209628; 2021-004151-16 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, a key secondary endpoints and safety data of the study.
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

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