All Japanese Population: Belantamab Mafodotin Plus Pomalidomide and Dexamethasone (Pd) Versus Bortezomib Plus Pd in Relapsed/Refractory Multiple Myeloma

Phase 3Active Not RecruitingNCT06956170

GlaxoSmithKline21 enrolled

Overview

This study will evaluate the efficacy and safety of belantamab mafodotin in combination with pomalidomide and dexamethasone compared with that of combination of pomalidomide, bortezomib and dexamethasone in Japanese participants with relapsed/refractory multiple myeloma (RRMM).

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 will be administered.

PomalidomideDRUG

Immunomodulatory drug (IMiD) will be administered.

DexamethasoneDRUG

Synthetic glucocorticoid with anti-tumor activity will be administered.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Capable of giving signed informed consent. * Male or female, 18 years or older. * Have a confirmed diagnosis of multiple myeloma (MM) as defined by the International Myeloma Working Group (IMWG) criteria. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. * Have been previously treated with at least 1 prior line of MM therapy including a lenalidomide-containing regimen and must have documented disease progression during or after their most recent therapy. (Participants treated with lenalidomide ≥10 mg daily for at least 2 consecutive cycles are eligible). * Must have at least 1 aspect of measurable disease defined as one of the following; 1. Urine M-protein excretion greater than or equal to (≥)200 milligrams (mg) per 24-hour, or 2. Serum M-protein concentration ≥0.5 grams/deciliters (g/dL) (≥5.0 g/liter \[L\]), or 3. Serum free light chain (FLC) assay: involved FLC level ≥10 mg/dL (≥100 mg/L) and an abnormal serum free light chain ratio (less than \[\<\]0.26 or greater than \[\>\]1.65) only if participant has no measurable urine or serum M spike. * Have undergone autologous stem cell transplant (ASCT) or are considered transplant ineligible. Participants with a history of ASCT are eligible for study participation provided the following eligibility criteria are met: a. ASCT was \>100 days prior to the first dose of study medication. b. No active bacterial, viral, or fungal infection(s) present * All prior treatment-related toxicities (defined by National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI-CTCAE\] version 5.0) must be less than or equal to (≤)Grade 1 at the time of enrolment, except for alopecia. * Adequate organ system functions as mentioned in the protocol. * Male and female participants agree to abide by protocol-defined contraceptive requirements. * In Japan, Hepatitis B participants who are hepatitis B surface antigen (HbsAg)- (e.g. HBsAb+/HbsAg-, HBcAb+/HbsAg-, HBcAb+/HBsAb+/HbsAg-) are eligible for inclusion in this study if hepatitis B virus (HBV) DNA is undetectable. A patient with HBsAg+ is eligible if HBV DNA is undetectable after assessing hepatitis B e antigen (HBeAg), hepatitis B e antibody (HBeAb) and HBV DNA, and if a hepatologist agrees with the participation into this study. Exclusion Criteria: * Active plasma cell leukemia, symptomatic amyloidosis or active polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, and skin changes (POEMS) syndrome at the time of screening. * Prior allogeneic SCT. * Systemic anti-myeloma therapy (including chemotherapy and systemic steroids) within 14 days or five half-lives (whichever is shorter) preceding the first dose of study drug; prior treatment with a monoclonal antibody drug within 30 days of receiving the first dose of study drugs. * Plasmapheresis within 7 days prior to the first dose of study drug. * Received prior treatment with or intolerant to pomalidomide. * Received prior Beta cell maturation antigen (BCMA) targeted therapy. * Intolerant to bortezomib or refractory to bortezomib (for example; participant experienced progressive disease during treatment, or within 60 days of completing treatment, with a bortezomib-containing regimen of 1.3 mg/meter square \[m\^2\] twice weekly). * Evidence of cardiovascular risk including any of the following; 1. Evidence of current clinically significant untreated arrhythmias, including clinically significant electrocardiogram abnormalities including second degree (Mobitz type II) or third degree atrioventricular (AV) block. 2. Recent history within (3 months of screening) of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting . 3. Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system 4. Uncontrolled hypertension. * Any major surgery within the last 4 weeks. * Previous or concurrent invasive malignancy other than multiple myeloma, except: 1. The disease must be considered medically stable for at least 2 years; or 2. The participant must not be receiving active therapy, other than hormonal therapy for this disease. * Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to belantamab mafodotin or drugs chemically related to belantamab mafodotin, or any of the components of the study treatment. * Evidence of active mucosal or internal bleeding. * Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice. * Active infection requiring treatment. * Known or active human immunodeficiency virus (HIV) infection, hepatitis B or hepatitis C will be excluded unless the protocol-defined criteria are met. * Presence of active renal conditions (such as infection, severe renal impairment requiring dialysis or any other condition that could affect participant's safety). * Ongoing Grade 2 peripheral neuropathy with pain within 14 days prior to randomization or ≥Grade 3 peripheral neuropathy. * Active or history of venous and arterial thromboembolism within the past 3 months. * Contraindications to or unwilling to undergo protocol-required anti-thrombotic prophylaxis. * Current corneal disease except for mild punctate keratopathy. * Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions (including laboratory abnormalities) that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures. * Pregnant or lactating female.

Locations (13)

GSK Investigational Site

Nagoya, Aichi-ken, Japan

GSK Investigational Site

Kamogawa, Chiba, Japan

GSK Investigational Site

Kashiwa, Chiba, 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 is defined as 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 120 weeks

Secondary Outcomes

Overall Survival (OS)

Overall Survival (OS) defined as the interval of time from randomization to the date of death due to any cause.

Time frame: Up to approximately 407 weeks

Duration of Response (DoR)

Duration of Response (DoR) defined as the time from first documented evidence of partial response (PR) or better until progressive disease (PD) or death due to any cause. Response will be based on IRC-assessment per IMWG criteria.

Time frame: Up to approximately 407 weeks

Minimal Residual Disease (MRD) Negativity Rate

MRD negativity rate defined as the percentage of participants who achieve MRD negative status (as assessed by NGS at 10\^5 threshold) at least once during the time of confirmed CR or better response based on IRC-assessment per IMWG.

Time frame: Up to approximately 407 weeks

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Proteasome Inhibitor will be administered.

GSK Investigational Site

Matsuyama, Ehime, Japan

GSK Investigation Site

Fukushima, Fukushima, Japan

GSK Investigational Site

Maebashi, Gunma, Japan

GSK Investigational Site

Shibukawa, Gunma, Japan

GSK Investigational Site

Numakunai, Iwate, Japan

GSK Investigational Site

Okayama, Okayama-ken, Japan

GSK Investigational Site

Osaka, Osaka, Japan

...and 3 more locations

Overall Response Rate (ORR)

ORR is defined as the percentage of participants with a confirmed partial response or better (i.e., PR, VGPR, CR, and sCR) based on IRC-assessment per IMWG criteria.

Time frame: Up to approximately 407 weeks

Complete Response Rate (CRR)

Complete Response Rate (CRR), defined as the percentage of participants with a confirmed complete response (CR) or better (i.e., CR and stringent complete response (sCR)) based on IRC assessment per IMWG criteria.

Time frame: Up to approximately 407 weeks

Percentage of Participants With a Confirmed Very Good Partial Response (VGPR) or Better

VGPR is defined as the percentage of participants with a confirmed VGPR or better (i.e., VGPR, CR, and sCR) based on IRC-assessment per IMWG criteria.

Time frame: Up to approximately 407 weeks

Time to Best Response (TTBR)

Time to Best Response (TTBR) defined as the interval of time between the date of randomization and the earliest date of achieving best response among participants with a confirmed PR or better based on IRC-assessment per IMWG.

Time frame: Up to approximately 407 weeks

Time to Response (TTR)

Time to Response (TTR) defined as the time between the date of randomization and the first documented evidence of response (PR or better) among participants who achieve a response (i.e., confirmed PR or better) based on IRC-assessment per IMWG.

Time frame: Up to approximately 407 weeks

Time to Progression (TTP)

Time to Progression (TTP) defined as the time from randomization until the earliest date of PD based on IRC-assessment per IMWG criteria, or death due to PD.

Time frame: Up to approximately 407 weeks

Progression-free Survival on Subsequent Line of Therapy (PFS2)

PFS2 defined as time from randomization to disease progression (investigator-assessed response) after initiation of new anti-myeloma therapy or death from any cause, whichever is earlier. 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.

Time frame: Up to approximately 407 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 approximately 407 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 approximately 407 weeks

Number of Participants With Clinically Significant Changes in Clinical Chemistry Parameters

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

Time frame: Up to approximately 407 weeks

Number of Participants With Abnormal Ocular Findings on Ophthalmic Examination

Time frame: Up to approximately 407 weeks

Plasma Concentrations of Belantamab Mafodotin (ADC)

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

Time frame: Up to approximately 407 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 approximately 407 weeks

Area Under Plasma Concentration-time Curve (AUC) From Time 0 to the Time of the Last Quantifiable Concentration (C(Tlast)) [AUC (0-last)] for Pomalidomide

Blood samples will be collected for PK analysis of Pomalidomide in combination with belantamab mafodotin and dexamethasone

Time frame: Up to approximately 407 weeks

Area Under Plasma Concentration-time Curve (AUC) From Time 0 to End of the Dosing Interval [AUC (0-tau)] for Pomalidomide

Blood samples will be collected for PK analysis of Pomalidomide in combination with belantamab mafodotin and dexamethasone.

Time frame: Up to approximately 407 weeks

Maximum Concentration (Cmax) for Pomalidomide

Blood samples will be collected for PK analysis of Pomalidomide in combination with belantamab mafodotin and dexamethasone.

Time frame: Up to approximately 407 weeks

Time of Cmax (Tmax) for Pomalidomide

Blood samples will be collected for PK analysis of Pomalidomide in combination with belantamab mafodotin and dexamethasone.

Time frame: Up to approximately 407 weeks

Trough Concentration Prior to the Next Dose for Each Cycle (Ctrough) for Pomalidomide

Blood samples will be collected for PK analysis of Pomalidomide in combination with belantamab mafodotin and dexamethasone.

Time frame: Up to approximately 407 weeks

Last Time Point Where the Concentration is Above the Limit of Quantification (Tlast) for Pomalidomide

Blood samples will be collected for PK analysis of Pomalidomide in combination with belantamab mafodotin and dexamethasone.

Time frame: Up to approximately 407 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 approximately 407 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 approximately 407 weeks

Number of Participants With Maximum Post-baseline Changes in Patient-reported Outcome Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Scores for Each Item Attribute

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 approximately 407 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 includes 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 is defined as latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. Change from Baseline is calculated by subtracting Baseline value from the post-dose visit value.

Time frame: Baseline and up to approximately 407 weeks

Change From Baseline in HRQoL as Measured by EORTC QLQ-20-item Multiple Myeloma Module (MY20)

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. The individual component scores in the disease symptom domain are averaged and transformed linearly to a score ranging from 0 to 100. A high score for disease symptoms represents a high level of symptomatology or problems. A high score for Future Perspective and Body Image represents a high/healthy level of functioning. Baseline is defined as latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. Change from Baseline is calculated by subtracting Baseline value from the post-dose visit value.

Time frame: Baseline and up to approximately 407 weeks

Change From Baseline in HRQoL as Measured by EORTC Item Library 52 (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 to 100. A high score for disease symptoms represents a high level of symptomatology or problems. Baseline is defined as latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. Change from Baseline is calculated by subtracting Baseline value from the post-dose visit value.

Time frame: Baseline and up to approximately 407 weeks