Evaluation of Efficacy and Safety of Belantamab Mafodotin, Bortezomib and Dexamethasone Versus Daratumumab, Bortezomib and Dexamethasone in Participants With Relapsed/Refractory Multiple Myeloma
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT04246047
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
This is a Phase 3, randomized, open-label study designed to evaluate safety and efficacy of belantamab mafodotin in combination with bortezomib/dexamethasone (Arm A) versus daratumumab in combination with bortezomib/dexamethasone (Arm B) in the participants with relapsed recurrent multiple myeloma.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 494
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Confirmed diagnosis of multiple myeloma as defined by the International Myeloma Working Group (IMWG) criteria.
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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.
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Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
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Must have at least 1 aspect of measurable disease, defined as one of the following;
- Urine M-protein excretion >=200 mg per 24-hour, or
- Serum M-protein concentration >=0.5 grams per deciliter (g/dL), or
- 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).
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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.
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Adequate organ function
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Daratumumab and Bortezomib plus Dexamethasone (Arm B) Bortezomib - Daratumumab and Bortezomib plus Dexamethasone (Arm B) Dexamethasone - Daratumumab and Bortezomib plus Dexamethasone (Arm B) Daratumumab - Belantamab mafodotin and Bortezomib plus Dexamethasone (Arm A) Bortezomib - Belantamab mafodotin and Bortezomib plus Dexamethasone (Arm A) Dexamethasone - Belantamab mafodotin and Bortezomib plus Dexamethasone (Arm A) Belantamab mafodotin -
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) Up to approximately 41 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 Outcome Measures
Name Time Method Complete Response Rate (CRR) Up to 73 months CRR is defined as percentage of participants with a confirmed complete response or better.
Overall Response Rate (ORR) Up to 73 months ORR is defined as percentage of participants with a confirmed partial response or better.
Clinical Benefit Rate (CBR) Up to 73 months CBR is defined as percentage of participants with a confirmed minimal response (MR) or better
Duration of Response (DoR) 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.
Time to Response (TTR) 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.
Time to Progression (TTP) 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.
Overall Survival (OS) Up to 73 months OS is defined as time from the date of randomization until the date of death due to any cause.
Progression-free Survival on Subsequent Line of Therapy (PFS2) 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.
Minimal Residual Disease (MRD) Negativity Rate 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).
Number of Participants With Adverse Events (AEs) 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.
Number of Participants With Clinically Significant Changes in Hematology Parameters Up to 73 months Blood samples will be collected for the analysis of hematology parameters.
Number of Participants With Clinically Significant Changes in Clinical Chemistry Up to 73 months Blood samples will be collected for the analysis of clinical chemistry parameters.
Number of Participants With Clinically Significant Changes in Urine Dipstick Up to 73 months Urine samples will be collected for the urine dipstick analysis.
Number of Participants With Abnormal Ocular Findings on Ophthalmic Examination Up to 73 months Plasma Concentrations of Belantamab Mafodotin (Total Antibody) at Indicated Time Points Up to 73 months Blood samples will be collected for PK analysis of belantamab mafodotin.
Plasma Concentrations of Belantamab Mafodotin (ADC) at Indicated Time Points Up to 73 months Blood samples will be collected for PK analysis of belantamab mafodotin.
Plasma Concentrations of Monomethyl Auristatin-F With a Cysteine Linker (Cys-mcMMAF) at Indicated Time Points Up to 73 months 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 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.
Titers of ADAs Against Belantamab Mafodotin 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.
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 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.
Change From Baseline in Health Related Quality of Life (HRQoL) as Measured by EuropeanOrganization for Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core Module (EORTC QLQ-C30) 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.
Change From Baseline in HRQoL as Measured by EORTC IL52 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.
Trial Locations
- Locations (1)
GSK Investigational Site
🇬🇧Sutton, United Kingdom
GSK Investigational Site🇬🇧Sutton, United Kingdom