Study of Single Agent Belantamab Mafodotin Versus Pomalidomide Plus Low-dose Dexamethasone (Pom/Dex) in Participants With Relapsed/Refractory Multiple Myeloma (RRMM)

Primary Outcome Measures

1. Progression-Free Survival (PFS) Based on Investigator-Assessed Response as Per International Myeloma Working Group (IMWG)
   PFS is time from randomization until earliest date of progressive disease (PD), or death due to any cause per investigator-assessed response per IMWG. PD is ≥25% increase from nadir in any of following: serum M-protein (absolute increase ≥0.5 gram per deciliter \[g/dL\]),urine M-protein(absolute increase ≥200 mg/24hr),difference between involved/uninvolved FLC levels (absolute increase \>10 mg/dL) in patients without measurable serum and urine M-protein levels, or bone marrow plasma-cell percentage irrespective of baseline status (absolute increase ≥10%) in patients without measurable serum and urine M-protein levels and without measurable involved FLC levels; appearance of new lesion,≥50% increase in longest diameter of a lesion previously measured \>1cm in short axis, or ≥50% increase from nadir in sum of products of two longest perpendicular diameters of more than 1 lesion; ≥50% increase in circulating plasma cells (minimum of 200 cells/microliter) if this is only measure of disease.

Secondary Outcome Measures

1. Overall Survival (OS)
   OS is defined as the time from randomization until death due to any cause.
2. Overall Response Rate (ORR)
   Overall Response Rate is defined as the percentage of participants with a confirmed partial response (PR) or better (i.e., PR, very good partial response \[VGPR\], complete response \[CR\] and stringent complete response \[sCR\]), according to the International Myeloma Working Group (IMWG) Response Criteria. PR: ≥50% reduction of serum M-protein and reduction in 24-hour (h) urinary M-protein by ≥90% or to \<200 mg/24-h; VGPR: serum and urine M-component detectable by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-component plus urine M-component \<100 mg/24-h; CR:negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND \<5% plasmacytomas in the bone marrow; sCR:stringent complete response, CR as above PLUS normal serum free light-chain (FLC) assay ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence.
3. Clinical Benefit Rate (CBR)
   Clinical benefit rate is defined as the percentage of participants with a confirmed minimal response (MR) or better according to the IMWG Response Criteria. MR is \>= 25% but \< 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%.
4. Duration of Response (DoR)
   Duration of response is defined as the time from first documented evidence of PR or better, to the time when disease progression (PD) is documented per IMWG response criteria; or death due to PD occurs among participants who achieve an overall response, i.e. confirmed PR or better. PD= Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 g/dL; Serum M-protein increase \>= 1 g/dL if the lowest M-component was \>=5 g/dL; Urinary M-protein (absolute increase must be \>= 200 mg per 24 h). PR = ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥ 90% or to \<200 mg/24 h.
5. Time to Response (TTR)
   TTR is defined as the time between the date of randomization and the first documented evidence of response (PR or better) among participants who achieve confirmed PR or better. PR: \>=50% reduction of serum M-protein \& reduction in 24h urinary M-protein by \>=90%/\<200mg/24 h.
6. Time to Progression (TTP)
   TTP is defined as the time from the date of randomization until the earliest date of documented PD (per IMWG Response Criteria) or death due to PD. PD: increase of \>=25% from lowest confirmed value in any 1 of following criteria: serum M-protein (absolute increase must be \>=0.5 g/dL), serum M-protein increase \>=1g/dL if lowest M component was \>=5g/dL; urine M-component (absolute increase must be \>=200mg/24 hour),appearance of new lesion(s), \>=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 the longest diameter of previous lesion \>1 cm in short axis.
7. Number of Participants With Treatment Emergent Adverse Events (TEAEs)
   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. TEAE is an event that emerged during treatment having been absent pre-treatment or worsened relative to the pre-treatment state. AEs were to be coded using the Medical Dictionary for Regulatory Activities (MedDRA) coding system.
8. Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-baseline Relative to Baseline
   Blood samples were collected for evaluation of hematology parameters. The summaries of worst-case change from Baseline with respect to normal range have been presented for only those laboratory tests that are gradable by CTCAE v5.0. The number of participants with decreases to low from baseline, changes to normal or no changes from baseline, and increases to high values have been presented. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. \[Basophils (Baso), Mean Corpuscular Hemoglobin Concentration (MCHC), Mean Corpuscular Hemoglobin (MCH), Mean Corpuscular Volume (MCV), Erythrocytes (Ery), Hematocrit (Hct), Monocytes (Mono), Reticulocytes (Ret), Leukocytes (Leu), Eosinophils (Eosi), Lymphocytes (Lym), Neutrophils (Neu)\]
9. Number of Participants With Maximum Grade Increase Post-Baseline Relative to Baseline in Hematology
   Blood samples were collected for evaluation of hematology parameters. The summaries of maximum grade increase from Baseline with respect to normal range have been presented for only those laboratory tests that are gradable by CTCAE version 5.0. Grade 1 (G1): mild; Grade 2 (G2): moderate; Grade 3 (G3): severe; Grade 4 (G4) life-threatening or disabling. Higher grade indicates greater severity and an increase in CTCAE grade was defined relative to the Baseline grade. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. \[White Blood Cells (WBC)\]
10. Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-baseline Relative to Baseline
    Blood samples were collected for evaluation of clinical chemistry parameters. The summaries of worst-case change from Baseline with respect to normal range have been presented for only those laboratory tests that are gradable by CTCAE v5.0. The number of participants with decreases to low from baseline, changes to normal or no changes from baseline, and increases to high values have been presented. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. \[Kappa Light (K Lt), Lambda (λ),Monoclonal (Mc), Protein (P), Change (Cge), Alpha (α), Beta (β), Creatine Kinase (CK), Gamma (γ) ,Immunoglobulin (I-Globulin), Indirect (In.)\]
11. Number of Participants With Maximum Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry
    Blood samples were collected for evaluation of clinical chemistry parameters. The summaries of maximum grade increase from Baseline with respect to normal range have been presented for only those laboratory tests that are gradable by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.Grade 1 (G1): mild; Grade 2 (G2): moderate; Grade 3 (G3): severe; Grade 4 (G4) life-threatening or disabling. Higher grade indicates greater severity and an increase in CTCAE grade was defined relative to the Baseline grade. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. \[Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), Aspartate Aminotransferase (AST), Creatine Kinase (CPK), Gamma Glutamyl Transferase (GGT)\]
12. Number of Participants With Shift in Urine Albumin Creatinine Ratio From Baseline to Worst Post-Baseline
    Urine samples were analyzed for spot urine albumin/creatinine ratio (UACR)\[milligrams/grams (mg/g)\]. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. The "worst post-baseline value" is defined as the highest UACR measurement recorded for a participant after the baseline assessment and up to the end of the study observation period. The "shift" will be calculated as the difference between this worst post-baseline UACR value and the baseline UACR value (Worst Post-Baseline UACR - Baseline UACR). Each category is reported as "Baseline category, Worst post-baseline category." Ranges are inclusive and expressed as \[lower-upper\].
13. Number of Participants With Maximum Worst-case Change From Baseline in Best Corrected Visual Acuity Test (BCVA) Scores
    BCVA score was assessed individually for each eye. BCVA score was calculated based on the Logarithm of the Minimum Angle of Resolution (logMAR score). Any worst-case change from baseline categories are presented for right and left eyes. BCVA test scores were categorized as no change/improved vision, possible worsened vision and definite worsened vision. No change/improved vision was defined as a change from baseline \<0.12 logMAR score; a possible worsened vision was defined as a change from baseline \>=0.12 to \<0.3 logMAR score; a definite worsened vision was defined as a change from baseline \>=0.3 logMAR score. Baseline (Day 1) was defined as latest pre-dose assessment with non-missing value, including unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
14. Observed Plasma Concentrations of Belantamab Mafodotin- Antibody-drug Conjugate (ADC)
    Blood samples were collected at indicated time points for pharmacokinetic analysis of belantamab mafodotin
15. Observed Plasma Concentrations of Belantamab Mafodotin- Total Monoclonal Antibody (mAb)
    Blood samples were collected at indicated time points for pharmacokinetic analysis of belantamab mafodotin
16. Observed Plasma Concentrations of Belantamab Mafodotin-Cys-mc Microtubular Inhibitor Monomethyl Auristatin-F (MMAF)
    Blood samples were collected at indicated time points for pharmacokinetic analysis of belantamab mafodotin
17. Number of Participants With Post-baseline Positive Anti-Drug Antibody (ADAs) Against Belantamab Mafodotin
    Serum samples collected for the analysis of the presence of ADAs using validated immunoassays. All samples were tested in screening assay, and positive samples were further characterized for antibody titers.
18. Titers of ADAs Against Belantamab Mafodotin
    Serum samples were collected and tested for the presence of antibodies against belantamab mafodotin . Confirmed positive ADA samples were further analyzed to obtain the titer of the antibodies. Titers of anti-drug antibodies against belantamab mafodotin is presented.
19. Number of Participants With Symptomatic Adverse Effects as Measured by the Patient Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
    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. It includes symptomatic toxicities drawn from the CTCAE like blurred vision, chills, constipation, decreased appetite, fatigue, general pain, mouth/throat sores, nausea, nosebleed, shortness of breath, vomiting, watery eyes, cough, itchy, loose/watery stools, Numb/Tingling Hands/Feet (N/T H/F), Pain/Burning (P/B) and Problems Tasting Food/Drink (Prob Tasting F/D) . Items are scored individually on a 0 to 4 scale for severity, frequency and interference. A score of 0 indicates no symptom or interference, while higher score of 4 signify increasing severity, frequency, and interference with daily activities.
20. Change From Baseline (CFB) in Ocular Surface Disease Index (OSDI) Total Score
    OSDI is 12-item patient-reported outcomes questionnaire designed to provide rapid assessment of range of ocular surface symptoms, including symptoms related to chronic dry eye, severity, and impact on patient's ability to function. In addition to an overall score, there are three subscales of OSDI: ocular symptoms, vision-related function, and environmental triggers. OSDI items are scored on a 0 to 4 Likert-type scale, where 0 = None of the time and 4 = All of the time. Total OSDI score = (\[sum of scores for all questions answered×100\]/\[total number of questions answered×4\]). Subscale scores are computed similarly with only questions from each subscale used to generate its own score. Any subscales analyzed separately would also have a maximum possible score of 100. A score of 100=to complete disability, while a score of 0=to no disability. Decrease in score from baseline means improvement
21. Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core Module (EORTC QLQ-C30) Score.
    The EORTC QLQ-C30 includes 30-items with single and multi-item scales. These included five functional scales (physical functioning \[PF\], role functioning \[RF\], emotional functioning \[EF\] cognitive functioning \[CF\] and social functioning \[SF\]), three symptom scales (fatigue, nausea/vomiting \[N/V\] and pain), a global health status (GHS)/ Quality-of-Life (QoL) scale, and six single items (dyspnea, insomnia, appetite loss \[AL\], constipation, diarrhea 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 the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
22. Change From Baseline (CFB) in EORTC QLQ 20-item Multiple Myeloma Module (MY20) Score
    The EORTC QLQ-MY20 is a supplement to the QLQ-C30 instrument used in participants with multiple myeloma. The module comprised of 20 questions that addressed four myeloma-specific HRQoL domains: disease symptoms (DS), side effects of treatment (SET), future perspective (FP) and body image (BI). Responses are 1 to 4. Scores were averaged and scales were transformed to 0 to 100 scale. A high score for disease symptoms and side effects of treatment represented a high level of symptomatology or problems, whereas a high score for future perspective and body image represented better outcomes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
23. Change From Baseline (CFB) in EORTC IL52 Score
    European Organization for Research and Treatment of Cancer Item Library 52 (EORTC-QLQ-IL52) is disease symptoms domain from EORTC Quality of Life Questionnaire 20-item Multiple Myeloma module) (EORTC QLQ-MY20). Disease symptoms domain of IL52 contain 6 items covering following concepts: bone aches or pain, back pain, hip pain, arm or shoulder pain, chest pain, and pain increasing with activity. IL52 items are scored on 1 to 4 Likert-type scale, where 1 = Not at all, 2 = A little, 3 = Quite a bit, and 4 = Very much. A raw score is then calculated as mean of completed item responses across 6 disease symptom items. For symptom scales, this raw score is linearly transformed to a 0 to 100 scale using the formula: \[(raw score - 1) / 3\] × 100. Under this approach, a score of 0 indicates no symptoms across items, while a score of 100 indicates the highest level of symptom burden. Accordingly, higher scores indicate greater symptom burden or worse disease symptoms
24. Number of Participants With Minimal Residual Disease (MRD) Negativity Rate
    MRD negativity rate is defined as the percentage of participants who are MRD negative by Next generation sequencing (NGS) method. The number of participants with MRD negativity has been presented