All Japanese Population: Belantamab Mafodotin Plus Pomalidomide and Dexamethasone (Pd) Versus Bortezomib Plus Pd in Relapsed/Refractory Multiple Myeloma
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT06956170
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 21
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Capable of giving signed informed consent.
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Male or female, 18 years or older.
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Have a confirmed diagnosis of multiple myeloma (MM) as defined by the International Myeloma Working Group (IMWG) criteria.
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Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
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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).
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Must have at least 1 aspect of measurable disease defined as one of the following;
- Urine M-protein excretion greater than or equal to (≥)200 milligrams (mg) per 24-hour, or
- Serum M-protein concentration ≥0.5 grams/deciliters (g/dL) (≥5.0 g/liter [L]), or
- 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.
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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
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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.
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Adequate organ system functions as mentioned in the protocol.
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Male and female participants agree to abide by protocol-defined contraceptive requirements.
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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.
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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.
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Prior allogeneic SCT.
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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.
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Plasmapheresis within 7 days prior to the first dose of study drug.
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Received prior treatment with or intolerant to pomalidomide.
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Received prior Beta cell maturation antigen (BCMA) targeted therapy.
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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).
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Evidence of cardiovascular risk including any of the following;
- Evidence of current clinically significant untreated arrhythmias, including clinically significant electrocardiogram abnormalities including second degree (Mobitz type II) or third degree atrioventricular (AV) block.
- Recent history within (3 months of screening) of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting .
- Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system
- Uncontrolled hypertension.
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Any major surgery within the last 4 weeks.
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Previous or concurrent invasive malignancy other than multiple myeloma, except:
- The disease must be considered medically stable for at least 2 years; or
- The participant must not be receiving active therapy, other than hormonal therapy for this disease.
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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.
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Evidence of active mucosal or internal bleeding.
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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.
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Active infection requiring treatment.
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Known or active human immunodeficiency virus (HIV) infection, hepatitis B or hepatitis C will be excluded unless the protocol-defined criteria are met.
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Presence of active renal conditions (such as infection, severe renal impairment requiring dialysis or any other condition that could affect participant's safety).
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Ongoing Grade 2 peripheral neuropathy with pain within 14 days prior to randomization or ≥Grade 3 peripheral neuropathy.
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Active or history of venous and arterial thromboembolism within the past 3 months.
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Contraindications to or unwilling to undergo protocol-required anti-thrombotic prophylaxis.
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Current corneal disease except for mild punctate keratopathy.
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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.
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Pregnant or lactating female.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Belantamab mafodotin plus Pomalidomide and Dexamethasone Belantamab mafodotin - Belantamab mafodotin plus Pomalidomide and Dexamethasone Pomalidomide - Belantamab mafodotin plus Pomalidomide and Dexamethasone Dexamethasone - Bortezomib plus Pomalidomide and Dexamethasone Pomalidomide - Bortezomib plus Pomalidomide and Dexamethasone Dexamethasone - Bortezomib plus Pomalidomide and Dexamethasone Bortezomib -
- Primary Outcome Measures
Name Time Method Progression-free survival (PFS) Up to approximately 120 weeks 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.
- Secondary Outcome Measures
Name Time Method Number of participants with abnormal ocular findings on ophthalmic examination Up to approximately 407 weeks Number of participants with adverse events (AEs) Up to approximately 407 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.
Number of participants with clinically significant changes in Clinical Laboratory Parameters 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 Up to approximately 407 weeks Blood samples will be collected for PK analysis of Pomalidomide in combination with belantamab mafodotin and dexamethasone.
Area Under Plasma Concentration-time Curve (AUC) From Time 0 to End of the Dosing Interval [AUC (0-tau)] for Pomalidomide Up to approximately 407 weeks Blood samples will be collected for PK analysis of Pomalidomide in combination with belantamab mafodotin and dexamethasone.
Maximum Concentration (Cmax) for Pomalidomide Up to approximately 407 weeks Blood samples will be collected for PK analysis of Pomalidomide in combination with belantamab mafodotin and dexamethasone.
Time of Cmax (Tmax) for Pomalidomide Up to approximately 407 weeks Blood samples will be collected for PK analysis of Pomalidomide in combination with belantamab mafodotin and dexamethasone.
Trough Concentration Prior to the Next Dose for Each Cycle (Ctrough) for Pomalidomide Up to approximately 407 weeks Blood samples will be collected for PK analysis of Pomalidomide in combination with belantamab mafodotin and dexamethasone.
Last Time Point Where the Concentration is Above the Limit of Quantification (Tlast) for Pomalidomide Up to approximately 407 weeks Blood samples will be collected for PK analysis of Pomalidomide in combination with belantamab mafodotin and dexamethasone.
Number of participants with positive anti-drug antibodies (ADAs) against belantamab mafodotin Up to approximately 407 weeks Titers of ADAs against belantamab mafodotin Up to approximately 407 weeks Complete response rate (CRR) Up to approximately 407 weeks 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.
Percentage of participants with a confirmed Very Good Partial Response (VGPR) or better Up to approximately 407 weeks 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 to best response (TTBR) Up to approximately 407 weeks 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 to response (TTR) Up to approximately 407 weeks 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 to progression (TTP) Up to approximately 407 weeks 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.
Progression-free survival on subsequent line of therapy (PFS2) Up to approximately 407 weeks 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.
Plasma concentrations of belantamab mafodotin (ADC) Up to approximately 407 weeks Blood samples will be collected for PK analysis of belantamab mafodotin.
Overall response rate (ORR) Up to approximately 407 weeks ORR will be 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.
Plasma concentrations of monomethyl auristatin-F with a cysteine linker (cys-mcMMAF) Up to approximately 407 weeks Blood samples will be collected for PK analysis of belantamab mafodotin.
Overall survival (OS) Up to approximately 407 weeks Overall Survival (OS) defined as the interval of time from randomization to the date of death due to any cause.
Duration of response (DoR) Up to approximately 407 weeks 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.
Minimal residual disease (MRD) negativity rate Up to approximately 407 weeks MRD negativity rate defined as the percentage of participants who achieve MRD negative status (as assessed by next-generation sequencing at 10\^5 threshold) at least once during the time of confirmed CR or better response based on IRC-assessment per IMWG.
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 Up to approximately 407 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 can range 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) Baseline and up to approximately 407 weeks The EORTC QLQ-C30 includes 30-items with single and multi-item scales. These include 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 will be 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.
Change from Baseline in HRQoL as measured by EORTC QLQ-20-item Multiple Myeloma Module (MY20) Baseline and up to approximately 407 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. 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 for Future Perspective and Body Image represents a high/healthy level of functioning.
Change from Baseline in HRQoL as measured by EORTC item library 52 (IL52) Baseline and up to approximately 407 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 will be 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.
Trial Locations
- Locations (2)
GSK Investigational Site
🇯🇵Hokkaido, Japan
GSK Investigation Site
🇯🇵Fukushima City, Fukushima-Ken, Japan