Trial Outcomes & Findings for Evaluation of Efficacy and Safety of Belantamab Mafodotin, Bortezomib and Dexamethasone Versus Daratumumab, Bortezomib and Dexamethasone in Participants With Relapsed/Refractory Multiple Myeloma (NCT NCT04246047)

Last Updated: 2024-10-24

Results Overview

PFS is defined as time from randomization until earliest date of disease progression (PD), determined by Independent Review Committee (IRC), according to the International Myeloma Working Group (IMWG) Response Criteria, or death due to any cause. PD= increase of \>=25% from lowest value in \>=1 of following (serum M-protein \[absolute increase \>=0.5 grams per deciliter {g/dL}\]; serum M-protein increase \>=1g/dL \[when lowest M-protein \>=5g/dL\]; urine M-protein \[absolute increase \>=200 milligrams per 24 hours {mg/24h}\]; participants without measurable serum \& urine M-protein levels, difference between involved \& uninvolved serum free light chains (sFLC) levels \[absolute increase \>10mg/dL\]; appearance of new lesion,\>=50% increase from nadir in Sum of the products of the maximal perpendicular diameters of measured lesions (SPD) of \>1 lesion, or \>=50% increase in longest diameter of previous lesion \>1 centimeter (cm) in short axis.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

494 participants

Primary outcome timeframe

Up to approximately 41 months

Results posted on

2024-10-24

Participant Flow

The results presented are until the primary completion date. Additional results will be provided within a year of study completion.

Participant milestones

Participant milestones
Measure	Belantamab Mafodotin + Bortezomib (Bor) + Dexamethasone (Dex) Participants with Relapsed/Refractory Multiple Myeloma (RRMM) received intravenous (IV) infusion of 2.5 milligram (mg)/kilogram (kg) belantamab mafodotin on Day 1 of each 21-day Cycle until disease progression, intolerable toxicity, death, informed consent withdrawal, or study end, whichever comes first in combination with 1.3 mg/meter\^2 (m\^2) Bor administered subcutaneously (SC) once daily on Days 1, 4, 8 and 11 of each 21-day cycle along with 20 mg Dex via oral tablet or IV infusion once daily on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for a total of 8 cycles.	Daratumumab + Bor + Dex Participants with RRMM received 16 mg/kg Daratumumab IV infusion once weekly of each 21-day cycle in Cycle 1 to Cycle 3; once every 3 weeks on Day 1 of each 21-day cycle in Cycle 4 to Cycle 8; and once every 4 weeks on day 1 of each 28-day cycle from cycle 9 onwards until disease progression, intolerable toxicity, death, informed consent withdrawal, or study end, whichever comes first in combination with 1.3 mg/m\^2 Bor administered SC once daily on Days 1, 4, 8 and 11 of each 21-day cycle along with 20 mg Dex oral tablet or IV infusion once daily on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for a total of 8 cycles.
Overall Study STARTED	243	251
Overall Study Safety Population	242	246
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	243	251

Reasons for withdrawal

Reasons for withdrawal
Measure	Belantamab Mafodotin + Bortezomib (Bor) + Dexamethasone (Dex) Participants with Relapsed/Refractory Multiple Myeloma (RRMM) received intravenous (IV) infusion of 2.5 milligram (mg)/kilogram (kg) belantamab mafodotin on Day 1 of each 21-day Cycle until disease progression, intolerable toxicity, death, informed consent withdrawal, or study end, whichever comes first in combination with 1.3 mg/meter\^2 (m\^2) Bor administered subcutaneously (SC) once daily on Days 1, 4, 8 and 11 of each 21-day cycle along with 20 mg Dex via oral tablet or IV infusion once daily on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for a total of 8 cycles.	Daratumumab + Bor + Dex Participants with RRMM received 16 mg/kg Daratumumab IV infusion once weekly of each 21-day cycle in Cycle 1 to Cycle 3; once every 3 weeks on Day 1 of each 21-day cycle in Cycle 4 to Cycle 8; and once every 4 weeks on day 1 of each 28-day cycle from cycle 9 onwards until disease progression, intolerable toxicity, death, informed consent withdrawal, or study end, whichever comes first in combination with 1.3 mg/m\^2 Bor administered SC once daily on Days 1, 4, 8 and 11 of each 21-day cycle along with 20 mg Dex oral tablet or IV infusion once daily on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for a total of 8 cycles.
Overall Study Death	50	77
Overall Study Lost to Follow-up	1	3
Overall Study Physician Decision	4	10
Overall Study Withdrawal by Subject	19	26
Overall Study Ongoing	169	135

Baseline Characteristics

Evaluation of Efficacy and Safety of Belantamab Mafodotin, Bortezomib and Dexamethasone Versus Daratumumab, Bortezomib and Dexamethasone in Participants With Relapsed/Refractory Multiple Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Belantamab Mafodotin + Bortezomib (Bor) + Dexamethasone (Dex) n=243 Participants Participants with Relapsed/Refractory Multiple Myeloma (RRMM) received intravenous (IV) infusion of 2.5 milligram (mg)/kilogram (kg) belantamab mafodotin on Day 1 of each 21-day Cycle until disease progression, intolerable toxicity, death, informed consent withdrawal, or study end, whichever comes first in combination with 1.3 mg/meter\^2 (m\^2) Bor administered subcutaneously (SC) once daily on Days 1, 4, 8 and 11 of each 21-day cycle along with 20 mg Dex via oral tablet or IV infusion once daily on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for a total of 8 cycles.	Daratumumab + Bor + Dex n=251 Participants Participants with RRMM received 16 mg/kg Daratumumab IV infusion once weekly of each 21-day cycle in Cycle 1 to Cycle 3; once every 3 weeks on Day 1 of each 21-day cycle in Cycle 4 to Cycle 8; and once every 4 weeks on day 1 of each 28-day cycle from cycle 9 onwards until disease progression, intolerable toxicity, death, informed consent withdrawal, or study end, whichever comes first in combination with 1.3 mg/m\^2 Bor administered SC once daily on Days 1, 4, 8 and 11 of each 21-day cycle along with 20 mg Dex oral tablet or IV infusion once daily on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for a total of 8 cycles.	Total n=494 Participants Total of all reporting groups
Age, Continuous	64.5 YEARS STANDARD_DEVIATION 9.47 • n=93 Participants	63.6 YEARS STANDARD_DEVIATION 10.11 • n=4 Participants	64.0 YEARS STANDARD_DEVIATION 9.80 • n=27 Participants
Sex: Female, Male Female	115 Participants n=93 Participants	107 Participants n=4 Participants	222 Participants n=27 Participants
Sex: Female, Male Male	128 Participants n=93 Participants	144 Participants n=4 Participants	272 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	30 Participants n=93 Participants	41 Participants n=4 Participants	71 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	213 Participants n=93 Participants	208 Participants n=4 Participants	421 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants

PRIMARY outcome

Timeframe: Up to approximately 41 months

Population: Intent-to-Treat (ITT) Population included of all randomized participants whether or not randomized treatment was administered.

Outcome measures

Outcome measures
Measure	Belantamab Mafodotin + Bortezomib (Bor) + Dexamethasone (Dex) n=243 Participants Participants with Relapsed/Refractory Multiple Myeloma (RRMM) received intravenous (IV) infusion of 2.5 milligram (mg)/kilogram (kg) belantamab mafodotin on Day 1 of each 21-day Cycle until disease progression, intolerable toxicity, death, informed consent withdrawal, or study end, whichever comes first in combination with 1.3 mg/meter\^2 (m\^2) Bor administered subcutaneously (SC) once daily on Days 1, 4, 8 and 11 of each 21-day cycle along with 20 mg Dex via oral tablet or IV infusion once daily on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for a total of 8 cycles.	Daratumumab + Bor + Dex n=251 Participants Participants with RRMM received 16 mg/kg Daratumumab IV infusion once weekly of each 21-day cycle in Cycle 1 to Cycle 3; once every 3 weeks on Day 1 of each 21-day cycle in Cycle 4 to Cycle 8; and once every 4 weeks on day 1 of each 28-day cycle from cycle 9 onwards until disease progression, intolerable toxicity, death, informed consent withdrawal, or study end, whichever comes first in combination with 1.3 mg/m\^2 Bor administered SC once daily on Days 1, 4, 8 and 11 of each 21-day cycle along with 20 mg Dex oral tablet or IV infusion once daily on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle for a total of 8 cycles.
Progression-free Survival (PFS)	36.6 Months Interval 28.4 to NA indicates the upper limit of 95% CI was not able to be estimated due to length of follow-up in assessing the number of events.	13.4 Months Interval 11.1 to 17.5

SECONDARY outcome

Timeframe: Up to 73 months

CRR is defined as percentage of participants with a confirmed complete response or better.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 73 months

ORR is defined as percentage of participants with a confirmed partial response or better.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 73 months

CBR is defined as percentage of participants with a confirmed minimal response (MR) or better

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 73 months

DOR is defined as time from first documented evidence of partial response or better until first documented progression or death, whichever occurs first.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 73 months

TTR is defined as time from the date of randomization and the first documented evidence of response (PR or better) among participants who achieve partial response or better.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 73 months

TTP is defined as time from the date of randomization until the earliest date of documented date of disease progression or death, whichever occurs first.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 73 months

OS is defined as time from the date of randomization until the date of death due to any cause.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 73 months

Progression-free survival on subsequent line of therapy is defined as time from randomization to disease progression after initiation of new anti-myeloma therapy or death from any cause, whichever occurs first. If disease progression after new antimyeloma therapy cannot be measured, a PFS event is defined as the date of discontinuation of new anti-myeloma therapy, or death from any cause, whichever is earlier.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 73 months

Minimal Residual Disease (MRD) negativity rate is defined as the percentage of participants who are MRD negative status by next generation sequencing (NGS).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 73 months

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 73 months

Blood samples will be collected for the analysis of hematology parameters.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 73 months

Blood samples will be collected for the analysis of clinical chemistry parameters.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 73 months

Urine samples will be collected for the urine dipstick analysis.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 73 months

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 73 months

Blood samples will be collected for PK analysis of belantamab mafodotin.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 73 months

Blood samples will be collected for PK analysis of belantamab mafodotin.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 73 months

Blood samples will be collected for PK analysis of belantamab mafodotin.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 73 months

Serum samples collected for the analysis of the presence of ADAs using validated immunoassays. All samples will be tested in screening assay, and positive samples will be further characterized for antibody titers.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 73 months

Serum samples collected for the analysis of the presence of ADAs using validated immunoassays. All samples will be to be further tested in screening assay, and positive samples will be further to be characterized for antibody titers.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 73 months

The PRO-CTCAE is a patient-reported outcome measure developed to evaluate symptomatic toxicity in participants on cancer clinical trials. The PRO-CTCAE includes an item library of 124 items representing 78 symptomatic toxicities drawn from the CTCAE.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 73 months

The EORTC QLQ-C30 includes 30-items with single and multi-item scales. These included five functional scales (physical functioning \[PF\], role functioning \[RF\], cognitive functioning \[CF\], emotional functioning \[EF\] and social functioning \[SF\]), three symptom scales (fatigue, pain and nausea/vomiting \[N/V\]), a global health status (GHS)/ Quality-of-Life (QoL) scale, and six single items (constipation, diarrhoea, insomnia, dyspnoea, appetite loss \[AL\] and financial difficulties \[FD\]). Response options are 1 to 4. Scores were averaged and transformed to 0 to 100, a high score for functional scales/ GHS/QoL represent better functioning ability or health-related quality-of-life (HRQoL), whereas a high score for symptom scales/ single items represent significant symptomatology. Baseline was defined as latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 73 months

The EORTC Quality of Life Questionnaire 20-item Multiple Myeloma module (QLQMY20) is a supplement to the QLQ-C30 instrument used in participants with multiple myeloma. For the EORTC IL52, disease symptoms domain of the QLQ-MY20 will be used for bone aches or pain, back pain, hip pain, arm or shoulder pain, chest pain, and pain increasing with activity. The individual component scores in the disease symptom domain are averaged and transformed linearly to a score ranging from 0 to100. A high score for disease symptoms represents a high level of symptomatology or problems. A high score represents a high/healthy level of functioning.

Outcome measures

Outcome data not reported

Adverse Events

Belantamab Mafodotin + Bortezomib (Bor) + Dexamethasone (Dex)

Serious events: 121 serious events

Other events: 238 other events

Deaths: 50 deaths

Daratumumab + Bor + Dex

Serious events: 90 serious events

Other events: 239 other events

Deaths: 77 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER