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

Phase 3Active Not RecruitingNCT06868667

GlaxoSmithKline24 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Multiple Myeloma

Interventions

Belantamab mafodotinDRUG

Humanized anti-B-cell maturation antigen (BCMA) antibody/drug conjugate.

DaratumumabDRUG

Anti-cluster of differentiation 38 \[CD-38\] monoclonal antibody.

BortezomibDRUG

Proteasome Inhibitor.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (16)

GSK Investigational Site

Aomori, Japan

GSK Investigational Site

Fukuoka, Japan

GSK Investigational Site

Himeji, Japan

Outcomes

Primary Outcomes

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

Secondary Outcomes

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

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

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

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)).

Data from ClinicalTrials.gov

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Synthetic glucocorticoid with anti-tumor activity.

GSK Investigational Site

Kamakura, Japan

GSK Investigational Site

Kitakyushu, Japan

GSK Investigational Site

Kochi, Japan

GSK Investigational Site

Matsuyama, Japan

GSK Investigational Site

Nagoya, Japan

GSK Investigational Site

Okayama, Japan

GSK Investigational Site

Osaka, Japan

...and 6 more locations

Time frame: Up to 255 weeks

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

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

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

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

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

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

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

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

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

Number of Participants With Abnormal Ocular Findings on Ophthalmic Examination

Time frame: Up to 255 weeks

Plasma Concentrations of Belantamab Mafodotin (Total Antibody)

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

Time frame: Up to 255 weeks

Plasma Concentrations of Belantamab Mafodotin (ADC)

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

Time frame: Up to 255 weeks

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

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

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

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

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

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