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

Multiple Myeloma Clinical Trial

— DREAMM 14  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05064358
• Other study ID #: 209628
• Secondary ID: 2021-004151-16
• Status: Recruiting
• Phase: Phase 2
• Start date: March 3, 2022
• Est. completion date: September 6, 2024

Study information

• Verified date: April 2023
• Source: GlaxoSmithKline
• Contact: US GSK Clinical Trials Call Center
• Phone: 877-379-3718
• Email: GSKClinicalSupportHD[@]gsk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: September 6, 2024
• Est. primary completion date: May 13, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Belantamab mafodotin
Belantamab mafodotin will be administered.

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Capital Federal	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires
Argentina	GSK Investigational Site	Rosario	Santa Fe
Australia	GSK Investigational Site	East Melbourne	Victoria
Australia	GSK Investigational Site	Liverpool	New South Wales
Australia	GSK Investigational Site	Waratah	New South Wales
Australia	GSK Investigational Site	Woodville	South Australia
Brazil	GSK Investigational Site	Curitiba	Paraná
Brazil	GSK Investigational Site	Joinville	Santa Catarina
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	Rio de Janeiro
Brazil	GSK Investigational Site	Salvador	Bahía
Brazil	GSK Investigational Site	São Paulo
Brazil	GSK Investigational Site	São Paulo
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Montréal	Quebec
Canada	GSK Investigational Site	Oshawa	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
France	GSK Investigational Site	Avignon cedex 9
France	GSK Investigational Site	Le Mans
France	GSK Investigational Site	Nice Cedex 2
France	GSK Investigational Site	Orléans
France	GSK Investigational Site	Saint-Priest en Jarez
Germany	GSK Investigational Site	Cottbus	Brandenburg
Germany	GSK Investigational Site	Dortmund	Nordrhein-Westfalen
Germany	GSK Investigational Site	Dresden	Sachsen
Germany	GSK Investigational Site	Greifswald	Mecklenburg-Vorpommern
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Karlsruhe	Baden-Wuerttemberg
Germany	GSK Investigational Site	Oldenburg	Niedersachsen
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Haidari, Athens
Greece	GSK Investigational Site	Rio/Patras
Greece	GSK Investigational Site	Thessaloniki
India	GSK Investigational Site	Ahmedabad
India	GSK Investigational Site	Bangalore
India	GSK Investigational Site	Hyderabad
India	GSK Investigational Site	Kerala
India	GSK Investigational Site	Kolkata
India	GSK Investigational Site	Kolkata
India	GSK Investigational Site	Mumbai
India	GSK Investigational Site	Nashik	Maharashtra
India	GSK Investigational Site	Pondicherry
India	GSK Investigational Site	Pune
Ireland	GSK Investigational Site	Dublin
Ireland	GSK Investigational Site	Dublin
Italy	GSK Investigational Site	Alessandria	Piemonte
Italy	GSK Investigational Site	Ascoli Piceno	Marche
Italy	GSK Investigational Site	Bologna	Emilia-Romagna
Italy	GSK Investigational Site	Cagliari
Italy	GSK Investigational Site	Cona (FE)	Emilia-Romagna
Italy	GSK Investigational Site	Genova	Liguria
Italy	GSK Investigational Site	Meldola	Emilia-Romagna
Italy	GSK Investigational Site	Reggio Emilia	Emilia-Romagna
Italy	GSK Investigational Site	Rimini	Emilia-Romagna
Korea, Republic of	GSK Investigational Site	Busan
Korea, Republic of	GSK Investigational Site	Hwasun-gun, Jeollanam-do
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Mexico	GSK Investigational Site	Mexico	Ciudad De Mexico
Mexico	GSK Investigational Site	Mexico City	Ciudad De Mexico
Poland	GSK Investigational Site	Bydgoszcz
Poland	GSK Investigational Site	Gdansk
Poland	GSK Investigational Site	Katowice
Poland	GSK Investigational Site	Lublin
Poland	GSK Investigational Site	Nowy Sacz
Poland	GSK Investigational Site	Walbrzych
Poland	GSK Investigational Site	Warszawa
Poland	GSK Investigational Site	Wroclaw
Spain	GSK Investigational Site	Albacete
Spain	GSK Investigational Site	Alcorcón (Madrid)
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Cordoba
Spain	GSK Investigational Site	Gerona
Spain	GSK Investigational Site	Lleida
Spain	GSK Investigational Site	Oviedo	Asturias
Spain	GSK Investigational Site	Terrassa (Barcelona)
Spain	GSK Investigational Site	Valencia
Switzerland	GSK Investigational Site	Bern
Taiwan	GSK Investigational Site	Taichung
Taiwan	GSK Investigational Site	Taichung
Taiwan	GSK Investigational Site	Tainan
Taiwan	GSK Investigational Site	Taipei
Taiwan	GSK Investigational Site	Taipei
Thailand	GSK Investigational Site	Bangkok
Thailand	GSK Investigational Site	Bangkok
Thailand	GSK Investigational Site	Chiang Mai
Thailand	GSK Investigational Site	Khon Kaen
United Kingdom	GSK Investigational Site	Leicester
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	Stoke-on-Trent	Staffordshire
United States	GSK Investigational Site	Chattanooga	Tennessee
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Kansas City	Missouri
United States	GSK Investigational Site	Nashville	Tennessee
United States	GSK Investigational Site	New Port Richey	Florida
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Spokane	Washington
United States	GSK Investigational Site	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Canada,  France,  Germany,  Greece,  India,  Ireland,  Italy,  Korea, Republic of,  Mexico,  Poland,  Spain,  Switzerland,  Taiwan,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Cumulative event rate of corneal events to Week 16 (KVA scale)		Up to Week 16
Secondary	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
Secondary	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
Secondary	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
Secondary	Percentage of participants requiring dose reductions, dose delays, and study treatment discontinuation due to corneal events		Up to 12 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change in best corrected visual acuity (BCVA)	BCVA will be assessed as per Snellen (or Snellen-equivalent) chart.	Up to 12 months
Secondary	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
Secondary	Percentage of participants with very good partial response (VGPR) or better		Up to 12 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Overall survival (OS)	Time from the date of randomization until death due to any cause.	Up to 12 months
Secondary	Number of participants with AEs and serious AEs (SAEs)		Up to 12 months
Secondary	Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis laboratory parameters		Up to 12 months
Secondary	Percentage of participants requiring dose reductions, dose delays, and study treatment discontinuation due to any AEs		Up to 12 months
Secondary	Maximum concentration (Cmax) of belantamab mafodotin		Up to 12 months
Secondary	Time taken to reach Cmax (Tmax) of belantamab mafodotin		Up to 12 months
Secondary	Area under the concentration time-curve (AUC) of belantamab mafodotin		Up to 12 months
Secondary	Number of participants with positive anti-drug antibodies (ADAs) against belantamab mafodotin		Up to 12 months
Secondary	Titers of ADAs against belantamab mafodotin		Up to 12 months