Clinical trial NCT05064358: Study to Investigate Alternative Dosing Regimens of Belantamab Mafodotin in Participants With Relapsed or Refractory Multiple Myeloma
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Antibody drug conjugate
Belantamab mafodotin
BLENREP
DREAMM14
GSK2857916
Alternative dosing
Relapsed or refractory multiple myeloma
RRMM
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2021-10-01
Enrollment: 177
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Belantamab mafodotin will be administered using various dosing regimens.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence rate of Grade ≥2 Corneal events according to the keratopathy visual acuity (KVA) scale
timeFrame: Up to 12 months
Secondary outcomes:
measure: Cumulative event rate of corneal events to Week 16 (KVA scale)
timeFrame: Up to Week 16
measure: Incidence rate of corneal events by grade (KVA scale)
timeFrame: Up to 12 months
measure: Exposure adjusted incidence rate of corneal events by grade (KVA scale)
timeFrame: Up to 12 months
measure: Median duration of dose delay
timeFrame: Up to 12 months
measure: Percentage of participants requiring dose reductions, dose delays, and study treatment discontinuation due to corneal events
timeFrame: Up to 12 months
measure: Cumulative incidence of corneal events by grade
timeFrame: Up to 12 months
measure: Toxicity Index score by assessment/visit
timeFrame: Up to 12 months
measure: Duration of corneal events
timeFrame: Up to 12 months
measure: Percentage of time on study with corneal events
timeFrame: Up to 12 months
measure: Change in best corrected visual acuity (BCVA)
timeFrame: Up to 12 months
measure: Overall response rate (ORR)
timeFrame: Up to 12 months
measure: Percentage of participants with very good partial response (VGPR) or better
timeFrame: Up to 12 months
measure: Time to response (TTR)
timeFrame: Up to 12 months
measure: Duration of response (DoR)
timeFrame: Up to 12 months
measure: Time to progression (TTP)
timeFrame: Up to 12 months
measure: Progression-free survival (PFS)
timeFrame: Up to 12 months
measure: Overall survival (OS)
timeFrame: Up to 12 months
measure: Number of participants with AEs and serious AEs (SAEs)
timeFrame: Up to 12 months
measure: Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis laboratory parameters
timeFrame: Up to 12 months
measure: Percentage of participants requiring dose reductions, dose delays, and study treatment discontinuation due to any AEs
timeFrame: Up to 12 months
measure: Maximum concentration (Cmax) of belantamab mafodotin
timeFrame: Up to 12 months
measure: Time taken to reach Cmax (Tmax) of belantamab mafodotin
timeFrame: Up to 12 months
measure: Area under the concentration time-curve (AUC) of belantamab mafodotin
timeFrame: Up to 12 months
measure: Number of participants with positive anti-drug antibodies (ADAs) against belantamab mafodotin
timeFrame: Up to 12 months
measure: Titers of ADAs against belantamab mafodotin
timeFrame: Up to 12 months
Other outcomes:
Locations:
city: West Palm Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Kansas City
country: United States
facility: GSK Investigational Site
state: Missouri
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Chattanooga
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Capital Federal
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: GSK Investigational Site
city: Pilar
country: Argentina
facility: GSK Investigational Site
city: Rosario
country: Argentina
facility: GSK Investigational Site
city: Liverpool
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Newcastle
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Woodville
country: Australia
facility: GSK Investigational Site
state: South Australia
city: East Melbourne
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Joinville
country: Brazil
facility: GSK Investigational Site
city: Porto Alegre
country: Brazil
facility: GSK Investigational Site
city: Rio de Janeiro
country: Brazil
facility: GSK Investigational Site
city: Salvador
country: Brazil
facility: GSK Investigational Site
city: Sao Paulo
country: Brazil
facility: GSK Investigational Site
city: SAo Paulo
country: Brazil
facility: GSK Investigational Site
city: Oshawa
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Avignon cedex 9
country: France
facility: GSK Investigational Site
city: Nice Cedex 2
country: France
facility: GSK Investigational Site
city: OrlEans
country: France
facility: GSK Investigational Site
city: Cottbus
country: Germany
facility: GSK Investigational Site
city: Dresden
country: Germany
facility: GSK Investigational Site
city: Greifswald
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Rio Patras
country: Greece
facility: GSK Investigational Site
city: Ahmedabad
country: India
facility: GSK Investigational Site
city: Apex Wellness Hospital
country: India
facility: GSK Investigational Site
city: Hyderabad
country: India
facility: GSK Investigational Site
city: Kolkata
country: India
facility: GSK Investigational Site
city: Kolkata
country: India
facility: GSK Investigational Site
city: M S R Nagar Msrit Post
country: India
facility: GSK Investigational Site
city: Pune
country: India
facility: GSK Investigational Site
city: Sushrut Hospital And Research
country: India
facility: GSK Investigational Site
city: Dublin 8
country: Ireland
facility: GSK Investigational Site
city: Dublin 9
country: Ireland
facility: GSK Investigational Site
city: Alessandria
country: Italy
facility: GSK Investigational Site
city: Ascoli Piceno
country: Italy
facility: GSK Investigational Site
city: Cagliari
country: Italy
facility: GSK Investigational Site
city: Ferrara
country: Italy
facility: GSK Investigational Site
city: Genova
country: Italy
facility: GSK Investigational Site
city: Meldola FC
country: Italy
facility: GSK Investigational Site
city: Reggio Emilia
country: Italy
facility: GSK Investigational Site
city: Rimini
country: Italy
facility: GSK Investigational Site
city: Hwasun
country: Korea, Republic of
facility: GSK Investigational Site
city: Pusan
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Mexico City
country: Mexico
facility: GSK Investigational Site
city: Mexico City
country: Mexico
facility: GSK Investigational Site
city: Bydgoszcz
country: Poland
facility: GSK Investigational Site
city: Gdansk
country: Poland
facility: GSK Investigational Site
city: Katowice
country: Poland
facility: GSK Investigational Site
city: Lublin
country: Poland
facility: GSK Investigational Site
city: Poznan
country: Poland
facility: GSK Investigational Site
city: Torun
country: Poland
facility: GSK Investigational Site
city: Walbrzych
country: Poland
facility: GSK Investigational Site
city: Warszawa
country: Poland
facility: GSK Investigational Site
city: Wroclaw
country: Poland
facility: GSK Investigational Site
city: Albacete
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Cordoba
country: Spain
facility: GSK Investigational Site
city: Gerona
country: Spain
facility: GSK Investigational Site
city: Oviedo
country: Spain
facility: GSK Investigational Site
city: Terrassa - Barcelona
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Bern
country: Switzerland
facility: GSK Investigational Site
city: Taichung
country: Taiwan
facility: GSK Investigational Site
city: Taichung
country: Taiwan
facility: GSK Investigational Site
city: Tainan
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Bangkok
country: Thailand
facility: GSK Investigational Site
city: Bangkok
country: Thailand
facility: GSK Investigational Site
city: Chiangmai
country: Thailand
facility: GSK Investigational Site
city: Khon Kaen
country: Thailand
facility: GSK Investigational Site
city: Leicester
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: Stoke on Trent
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: