Multiple Myeloma
Conditions
Keywords
Japan Expansion Cohort, Belantamab mafodotin, Relapsed/refractory multiple myeloma, Daratumumab, Bortezomib, Dexamethasone, Multiple Myeloma
Brief summary
This study is designed to evaluate safety and efficacy of belantamab mafodotin in combination with bortezomib/dexamethasone versus daratumumab in combination with bortezomib/dexamethasone in the Japanese participants with relapsed refractory multiple myeloma.
Interventions
DRUGBelantamab mafodotin
Humanized anti-B-cell maturation antigen (BCMA) antibody/drug conjugate.
DRUGDaratumumab
Anti-cluster of differentiation 38 \[CD-38\] monoclonal antibody.
DRUGBortezomib
Proteasome Inhibitor.
DRUGDexamethasone
Synthetic glucocorticoid with anti-tumor activity.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of multiple myeloma as defined by the International Myeloma Working Group (IMWG) criteria. * Previously treated with at least 1 prior line of multiple myeloma (MM) therapy and must have documented disease progression during or after their most recent therapy. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. * Must have at least 1 aspect of measurable disease, defined as one of the following; 1. Urine M-protein excretion \>=200 mg per 24-hour, or 2. Serum M-protein concentration \>=0.5 grams per deciliter (g/dL), or 3. Serum free light chain (FLC) assay: involved FLC level \>=10 mg per dL (\>=100 mg per liter) and an abnormal serum free light chain ratio (\<0.26 or \>1.65). * All prior treatment-related toxicities (defined by National Cancer Institute Common Toxicity Criteria for Adverse Events \[NCI-CTCAE\] version 5.0) must be \<=Grade 1 at the time of enrollment, except for alopecia. * Adequate organ function
Exclusion criteria
* Intolerant to daratumumab. * Refractory to daratumumab or any other anti-CD38 therapy (defined as progressive disease during treatment with anti-CD38 therapy, or within 60 days of completing that treatment). * Intolerant to bortezomib, or refractory to bortezomib (defined as progressive disease during treatment with a bortezomib-containing regimen of 1.3 mg/m\^2 twice weekly, or within 60 days of completing that treatment). Note: participants with progressive disease during treatment with a weekly bortezomib regimen are allowed. * Ongoing Grade 2 or higher peripheral neuropathy or neuropathic pain. * Prior treatment with anti-B-cell maturation antigen (anti-BCMA) therapy. * Prior allogenic stem cell transplant. * Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions, including renal, liver, cardiovascular, or certain prior malignancies. * Corneal epithelial disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Up to approximately 32 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to 255 weeks | OS is defined as time from the date of randomization until the date of death due to any cause. |
| Duration of Response (DoR) | Up to 255 weeks | DOR is defined as time from first documented evidence of partial response or better until first documented progression or death, whichever occurs first. |
| Minimal Residual Disease (MRD) Negativity Rate | Up to 255 weeks | Minimal Residual Disease (MRD) negativity rate is defined as the percentage of participants who are MRD negative by next generation sequencing (NGS). |
| Complete Response Rate (CRR) | Up to 255 weeks | CRR is defined as percentage of participants with a confirmed complete response (CR) or better (i.e., CR, stringent Complete Response (sCR)). |
| Overall Response Rate (ORR) | Up to 255 weeks | ORR is defined as percentage of participants with a confirmed partial response (PR) or better (i.e. PR, Very Good Partial Response \[VGPR\], CR or sCR). |
| Clinical Benefit Rate (CBR) | Up to 255 weeks | CBR is defined as percentage of participants with a confirmed minimal response (MR) or better per International Myeloma Working Group (IMWG). |
| Time to Response (TTR) | Up to 255 weeks | 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. |
| Time to Progression (TTP) | Up to 255 weeks | TTP is defined as the time from the date of randomization until the earliest date of documented PD or death due to PD. 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. |
| Progression-free Survival on Subsequent Line of Therapy (PFS2) | Up to 255 weeks | PFS2 is defined as time from randomization to disease progression after initiation of new anti-myeloma therapy or death from any cause, whichever is earlier. If disease progression after new anti-myeloma 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 |
| Number of Participants With Adverse Events (AEs) | Up to 255 weeks | 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. AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA dictionary). |
| Number of Participants With Clinically Significant Changes in Hematology Parameters | Up to 255 weeks | Blood samples will be collected for the analysis of hematology parameters. |
| Number of Participants With Clinically Significant Changes in Clinical Chemistry | Up to 255 weeks | Blood samples will be collected for the analysis of clinical chemistry parameters. |
| Number of Participants With Clinically Significant Changes in Urine Dipstick | Up to 255 weeks | Urine samples will be collected for the urine dipstick analysis. |
| Number of Participants With Abnormal Ocular Findings on Ophthalmic Examination | Up to 255 weeks | — |
| Plasma Concentrations of Belantamab Mafodotin (Total Antibody) | Up to 255 weeks | Blood samples will be collected for PK analysis of belantamab mafodotin. |
| Plasma Concentrations of Belantamab Mafodotin (ADC) | Up to 255 weeks | Blood samples will be collected for PK analysis of belantamab mafodotin. |
| Plasma Concentrations of Monomethyl Auristatin-F With a Cysteine Linker (Cys-mcMMAF) | Up to 255 weeks | Blood samples will be collected for PK analysis of belantamab mafodotin. |
| Number of Participants With Positive Anti-Drug Antibodies (ADAs) Against Belantamab Mafodotin | Up to 255 weeks | Serum samples will be 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. |
| Titers of ADAs Against Belantamab Mafodotin | Up to 255 weeks | Serum samples will be collected for the analysis of the presence of ADAs using validated immunoassays. All samples will be further tested in screening assay, and positive samples will be further characterized for antibody titers. |
| Number of Participants With Maximum Post-baseline Change From Baseline in Individual Items of Patient-reported Outcome Version of the Common Term Criteria for Adverse Events (PRO-CTCAE) | Up to 255 weeks | The PRO-CTCAE is a patient-reported outcome measure that was developed to evaluate symptomatic toxicities in patients in cancer clinical trials; it characterizes the frequency, severity, interference, and presence or absence of symptomatic toxicities. Responses ranges from 0 ("never," "none," "not at all," or "absent") to 4 ("almost constantly," "very severe," or "very much"), with a higher score indicating a higher frequency, severity, or interference of adverse events. |
| Change From Baseline in Health Related Quality of Life (HRQoL) as Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core Module (EORTC QLQ-C30) | Up to 255 weeks | 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 are 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. |
| Change From Baseline in HRQoL as Measured by EORTC IL52 | Up to 255 weeks | 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. |
Countries
Japan
Participant flow
Pre-assignment details
The results presented are until the primary completion date. Additional results will be provided within a year of study completion.
Participants by arm
| Arm | Count |
|---|---|
| Belantamab Mafodotin + Bortezomib (Bor) + Dexamethasone (Dex) Japanese 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. | 10 |
| Daratumumab + Bor + Dex Japanese 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. | 14 |
| Total | 24 |
Baseline characteristics
| Characteristic | Belantamab Mafodotin + Bortezomib (Bor) + Dexamethasone (Dex) | Daratumumab + Bor + Dex | Total |
|---|---|---|---|
| Age, Continuous | 67.9 YEARS STANDARD_DEVIATION 11.02 | 70.9 YEARS STANDARD_DEVIATION 6.21 | 69.6 YEARS STANDARD_DEVIATION 8.46 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 14 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 5 Participants | 11 Participants | 16 Participants |
| Sex: Female, Male Male | 5 Participants | 3 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 4 / 14 |
| other Total, other adverse events | 10 / 10 | 14 / 14 |
| serious Total, serious adverse events | 7 / 10 | 2 / 14 |
Outcome results
Primary
Progression-free Survival (PFS)
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.
Time frame: Up to approximately 32 months
Population: Intent-to-Treat (ITT) Population included all randomized participants whether or not randomized treatment was administered.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Belantamab Mafodotin + Bortezomib (Bor) + Dexamethasone (Dex) | Progression-free Survival (PFS) | NA Months |
| Daratumumab + Bor + Dex | Progression-free Survival (PFS) | 11.1 Months |
95% CI: [0.11, 1.52]
Secondary
Change From Baseline in Health Related Quality of Life (HRQoL) as Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core Module (EORTC QLQ-C30)
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 are 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.
Time frame: Up to 255 weeks
Secondary
Change From Baseline in HRQoL as Measured by EORTC IL52
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.
Time frame: Up to 255 weeks
Secondary
Clinical Benefit Rate (CBR)
CBR is defined as percentage of participants with a confirmed minimal response (MR) or better per International Myeloma Working Group (IMWG).
Time frame: Up to 255 weeks
Secondary
Complete Response Rate (CRR)
CRR is defined as percentage of participants with a confirmed complete response (CR) or better (i.e., CR, stringent Complete Response (sCR)).
Time frame: Up to 255 weeks
Secondary
Duration of Response (DoR)
DOR is defined as time from first documented evidence of partial response or better until first documented progression or death, whichever occurs first.
Time frame: Up to 255 weeks
Secondary
Minimal Residual Disease (MRD) Negativity Rate
Minimal Residual Disease (MRD) negativity rate is defined as the percentage of participants who are MRD negative by next generation sequencing (NGS).
Time frame: Up to 255 weeks
Secondary
Number of Participants With Abnormal Ocular Findings on Ophthalmic Examination
Time frame: Up to 255 weeks
Secondary
Number of Participants With Adverse Events (AEs)
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. AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA dictionary).
Time frame: Up to 255 weeks
Secondary
Number of Participants With Clinically Significant Changes in Clinical Chemistry
Blood samples will be collected for the analysis of clinical chemistry parameters.
Time frame: Up to 255 weeks
Secondary
Number of Participants With Clinically Significant Changes in Hematology Parameters
Blood samples will be collected for the analysis of hematology parameters.
Time frame: Up to 255 weeks
Secondary
Number of Participants With Clinically Significant Changes in Urine Dipstick
Urine samples will be collected for the urine dipstick analysis.
Time frame: Up to 255 weeks
Secondary
Number of Participants With Maximum Post-baseline Change From Baseline in Individual Items of Patient-reported Outcome Version of the Common Term Criteria for Adverse Events (PRO-CTCAE)
The PRO-CTCAE is a patient-reported outcome measure that was developed to evaluate symptomatic toxicities in patients in cancer clinical trials; it characterizes the frequency, severity, interference, and presence or absence of symptomatic toxicities. Responses ranges from 0 (never, none, not at all, or absent) to 4 (almost constantly, very severe, or very much), with a higher score indicating a higher frequency, severity, or interference of adverse events.
Time frame: Up to 255 weeks
Secondary
Number of Participants With Positive Anti-Drug Antibodies (ADAs) Against Belantamab Mafodotin
Serum samples will be 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.
Time frame: Up to 255 weeks
Secondary
Overall Response Rate (ORR)
ORR is defined as percentage of participants with a confirmed partial response (PR) or better (i.e. PR, Very Good Partial Response \[VGPR\], CR or sCR).
Time frame: Up to 255 weeks
Secondary
Overall Survival (OS)
OS is defined as time from the date of randomization until the date of death due to any cause.
Time frame: Up to 255 weeks
Secondary
Plasma Concentrations of Belantamab Mafodotin (ADC)
Blood samples will be collected for PK analysis of belantamab mafodotin.
Time frame: Up to 255 weeks
Secondary
Plasma Concentrations of Belantamab Mafodotin (Total Antibody)
Blood samples will be collected for PK analysis of belantamab mafodotin.
Time frame: Up to 255 weeks
Secondary
Plasma Concentrations of Monomethyl Auristatin-F With a Cysteine Linker (Cys-mcMMAF)
Blood samples will be collected for PK analysis of belantamab mafodotin.
Time frame: Up to 255 weeks
Secondary
Progression-free Survival on Subsequent Line of Therapy (PFS2)
PFS2 is defined as time from randomization to disease progression after initiation of new anti-myeloma therapy or death from any cause, whichever is earlier. If disease progression after new anti-myeloma 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
Time frame: Up to 255 weeks
Secondary
Time to Progression (TTP)
TTP is defined as the time from the date of randomization until the earliest date of documented PD or death due to PD. 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.
Time frame: Up to 255 weeks
Secondary
Time to Response (TTR)
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.
Time frame: Up to 255 weeks
Secondary
Titers of ADAs Against Belantamab Mafodotin
Serum samples will be collected for the analysis of the presence of ADAs using validated immunoassays. All samples will be further tested in screening assay, and positive samples will be further characterized for antibody titers.
Time frame: Up to 255 weeks