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

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05064358

Collaborator

(none)

180

Enrollment

Locations

Arms

30.2

Anticipated Duration (Months)

3.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Belantamab mafodotin	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

180 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Belantamab mafodotin will be administered using various dosing regimens.Belantamab mafodotin will be administered using various dosing regimens.

Masking:

None (Open Label)

Masking Description:

It is an open label study

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Mar 3, 2022

Anticipated Primary Completion Date :

Mar 18, 2024

Anticipated Study Completion Date :

Sep 6, 2024

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

Incidence rate of Grade ≥2 ocular adverse events (AEs) according to the keratopathy visual acuity (KVA) scale [Up to 12 months]
KVA scale is used to grade the ocular AEs 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.

Secondary Outcome Measures

Cumulative event rate of ocular AEs to Week 16 (KVA scale) [Up to Week 16]
Incidence rate of ocular AEs by grade (KVA scale) [Up to 12 months]
KVA scale is used to grade the ocular AEs 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.
Exposure adjusted incidence rate of ocular AEs by grade (KVA scale) [Up to 12 months]
The exposure adjusted incidence rate is defined as the number of participants with ocular 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.
Median duration of dose delay [Up to 12 months]
Median duration of dose delay is defined as the median duration in time of all the dose delays in the respective treatment group.
Percentage of participants requiring dose reductions, dose delays, and study treatment discontinuation due to ocular AEs [Up to 12 months]
Cumulative incidence of ocular AEs by grade [Up to 12 months]
Cumulative incidence of ocular AEs 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
Toxicity Index score by assessment/visit [Up to 12 months]
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.
Duration of ocular AEs [Up to 12 months]
Duration of ocular AEs is defined as the sum of the duration of all the ocular AEs of a participant.
Percentage of time on study with ocular AEs [Up to 12 months]
Percentage of time on study with ocular AEs is defined as the duration of ocular AEs divided by the total amount of time that a participant is on the study in percentage.
Change in best corrected visual acuity (BCVA) [Up to 12 months]
BCVA will be assessed as per Snellen (or Snellen-equivalent) chart.
Overall response rate (ORR) [Up to 12 months]
Percentage of participants with a confirmed partial response (PR) or better per International Myeloma Working Group (IMWG) criteria.
Percentage of participants with very good partial response (VGPR) or better [Up to 12 months]
Time to response (TTR) [Up to 12 months]
Time between the date of randomization and the first documented evidence of response (PR or better) among participants who achieve confirmed PR or better.
Duration of response (DoR) [Up to 12 months]
Time from first documented evidence of PR or better until progressive disease (PD) per IMWG or death due to any cause.
Time to progression (TTP) [Up to 12 months]
Time from the date of randomization until the earliest date of documented PD (per IMWG Response Criteria) or death due to PD.
Progression-free survival (PFS) [Up to 12 months]
Time from the date of randomization until the earliest date of documented PD (according to IMWG Response Criteria) or death due to any cause.
Overall survival (OS) [Up to 12 months]
Time from the date of randomization until death due to any cause.
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]
Plasma concentrations of total monoclonal antibody (mAb) [Up to 12 months]
Blood sample for total mAb will be collected at each ADA time point.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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-MM 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).
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.
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 after consultation with the GSK medical director.
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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Houston	Texas	United States	77090
2	GSK Investigational Site	Spokane	Washington	United States	99218
3	GSK Investigational Site	Liverpool	New South Wales	Australia	2170
4	GSK Investigational Site	Waratah	New South Wales	Australia	2298
5	GSK Investigational Site	Woodville	South Australia	Australia	5011
6	GSK Investigational Site	Joinville	Santa Catarina	Brazil	89201-260
7	GSK Investigational Site	São Paulo		Brazil	04537-080
8	GSK Investigational Site	Montreal	Quebec	Canada	H2L 4M1
9	GSK Investigational Site	Montréal	Quebec	Canada	H4J 1C5
10	GSK Investigational Site	Avignon cedex 9		France	84902
11	GSK Investigational Site	Le Mans		France	72000
12	GSK Investigational Site	Nice Cedex 2		France	06189
13	GSK Investigational Site	Orléans		France	45100
14	GSK Investigational Site	Saint-Priest en Jarez		France	42270
15	GSK Investigational Site	Cottbus	Brandenburg	Germany	03048
16	GSK Investigational Site	Greifswald	Mecklenburg-Vorpommern	Germany	17475
17	GSK Investigational Site	Oldenburg	Niedersachsen	Germany	26133
18	GSK Investigational Site	Dresden	Sachsen	Germany	01307
19	GSK Investigational Site	Hamburg		Germany	22763
20	GSK Investigational Site	Nashik	Maharashtra	India	422009
21	GSK Investigational Site	Ahmedabad		India	380009
22	GSK Investigational Site	Hyderabad		India	500033
23	GSK Investigational Site	Pune		India	411004
24	GSK Investigational Site	Bologna	Emilia-Romagna	Italy	40138
25	GSK Investigational Site	Meldola	Emilia-Romagna	Italy	47014
26	GSK Investigational Site	Reggio Emilia	Emilia-Romagna	Italy	42123
27	GSK Investigational Site	Rimini	Emilia-Romagna	Italy	47900
28	GSK Investigational Site	Ascoli Piceno	Marche	Italy	63100
29	GSK Investigational Site	Busan		Korea, Republic of	49241
30	GSK Investigational Site	Hwasun-gun, Jeollanam-do		Korea, Republic of	58128
31	GSK Investigational Site	Seoul		Korea, Republic of	03080
32	GSK Investigational Site	Seoul		Korea, Republic of	06591
33	GSK Investigational Site	Bydgoszcz		Poland	85-168
34	GSK Investigational Site	Gdansk		Poland	80-214
35	GSK Investigational Site	Katowice		Poland	40-519
36	GSK Investigational Site	Lublin		Poland	20-081
37	GSK Investigational Site	Nowy Sacz		Poland	33-300
38	GSK Investigational Site	Warszawa		Poland	02-781
39	GSK Investigational Site	Oviedo	Asturias	Spain	33011
40	GSK Investigational Site	Albacete		Spain	02006
41	GSK Investigational Site	Alcorcón (Madrid)		Spain	28922
42	GSK Investigational Site	Cordoba		Spain	14004
43	GSK Investigational Site	Gerona		Spain	17007
44	GSK Investigational Site	Lleida		Spain	25198
45	GSK Investigational Site	Terrassa (Barcelona)		Spain	08221
46	GSK Investigational Site	Taichung		Taiwan	404
47	GSK Investigational Site	Taichung		Taiwan	40705
48	GSK Investigational Site	Tainan		Taiwan	704
49	GSK Investigational Site	Taipei		Taiwan	100
50	GSK Investigational Site	Taipei		Taiwan	112
51	GSK Investigational Site	Bangkok		Thailand	10330
52	GSK Investigational Site	Chiang Mai		Thailand	50200
53	GSK Investigational Site	Khon Kaen		Thailand	40002
54	GSK Investigational Site	London		United Kingdom	W12 0HS