| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT06679101 | A Study of Belantamab Mafodotin Administered in Combination With Lenalidomide and Dexamethasone (BRd) Versus Daratumumab, Lenalidomide, and Dexamethasone (DRd) in Participants With Newly Diagnosed Multiple Myeloma (NDMM) Who Are Ineligible for Autologous Stem Cell Transplantation (TI-NDMM) | PHASE3 | RECRUITING | 520 | — | — | Dec 16, 2024 | Apr 28, 2031 | Apr 22, 2026 | 181 | United States, Argentina +22 |
| NCT06956170 | All Japanese Population: Belantamab Mafodotin Plus Pomalidomide and Dexamethasone (Pd) Versus Bortezomib Plus Pd in Relapsed/Refractory Multiple Myeloma | PHASE3 | ACTIVE NOT_RECRUITING | 21 | — | — | Feb 10, 2022 | Nov 30, 2029 | Jun 11, 2025 | 13 | Japan |
| NCT06868667 | 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 | PHASE3 | ACTIVE NOT_RECRUITING | 24 | — | — | Jul 28, 2021 | Jun 30, 2028 | Apr 23, 2026 | 16 | Japan |
| NCT06868654 | China Subpopulation: Evaluation of Efficacy and Safety of Belantamab Mafodotin, Bortezomib and Dexamethasone Versus Daratumumab, Bortezomib and Dexamethasone in Participants With Relapsed/Refractory Multiple Myeloma | PHASE3 | ACTIVE NOT_RECRUITING | 72 | — | — | Jul 28, 2021 | Jun 30, 2028 | Apr 23, 2026 | 11 | China |
| NCT04484623 | Belantamab Mafodotin Plus Pomalidomide and Dexamethasone (Pd) Versus Bortezomib Plus Pd in Relapsed/Refractory Multiple Myeloma | PHASE3 | ACTIVE NOT_RECRUITING | 302 | — | — | Oct 1, 2020 | Oct 25, 2029 | Mar 18, 2025 | 119 | United States, Australia +16 |
| NCT04246047 | Evaluation of Efficacy and Safety of Belantamab Mafodotin, Bortezomib and Dexamethasone Versus Daratumumab, Bortezomib and Dexamethasone in Participants With Relapsed/Refractory Multiple Myeloma | PHASE3 | ACTIVE NOT_RECRUITING | 494 | — | — | May 7, 2020 | Jun 30, 2028 | Apr 23, 2026 | 69 | United States, Australia +11 |
| NCT04162210 | Study of Single Agent Belantamab Mafodotin Versus Pomalidomide Plus Low-dose Dexamethasone (Pom/Dex) in Participants With Relapsed/Refractory Multiple Myeloma (RRMM) | PHASE3 | ACTIVE NOT_RECRUITING | 325 | — | — | Apr 2, 2020 | Mar 11, 2027 | Mar 31, 2026 | 102 | United States, Australia +17 |
| NCT07614360 | Study of Alternative and Approved Dosing Regimens of Belantamab Mafodotin, Bortezomib, and Dexamethasone (BVd) in Participants With Relapsed/Refractory Multiple Myeloma | PHASE2 | NOT YET_RECRUITING | 120 | — | — | Aug 3, 2026 | Feb 11, 2031 | May 29, 2026 | - | — |
| NCT07227311 | A Study to Evaluate the Efficacy and Safety of Belantamab Mafodotin in Combination With Standard of Care in Participants With Relapsed-Refractory Multiple Myeloma (RRMM) | PHASE2 | RECRUITING | 200 | — | — | Apr 15, 2026 | Aug 30, 2030 | Jun 2, 2026 | 18 | United States, Germany +3 |
| NCT05064358 | Study to Investigate Alternative Dosing Regimens of Belantamab Mafodotin in Participants With Relapsed or Refractory Multiple Myeloma | PHASE2 | COMPLETED | 177 | — | — | Mar 3, 2022 | Feb 10, 2026 | May 5, 2026 | 77 | United States, Argentina +16 |
| NCT07609706 | A Study of the Combination of Belantamab Mafodotin, Bortezomib, and Dexamethasone (BVd) in Participants With Multiple Myeloma and Moderate Hepatic Impairment | PHASE1 | NOT YET_RECRUITING | 20 | — | — | Oct 23, 2026 | Aug 22, 2031 | May 27, 2026 | - | — |
| NCT07150104 | Sub-study of Belantamab Mafodotin (GSK2857916) as Monotherapy and in Combination With Nirogacestat, Pomalidomide, and Dexamethasone in Participants With RRMM | PHASE1 | ACTIVE NOT_RECRUITING | 14 | — | — | Aug 31, 2022 | Mar 11, 2027 | Sep 2, 2025 | 10 | Brazil, Canada +6 |
| NCT07150091 | Sub-study of Belantamab Mafodotin (GSK2857916) in Combination With Nirogacestat, Lenalidomide, and Dexamethasone in Participants With RRMM | PHASE1 | ACTIVE NOT_RECRUITING | 20 | — | — | Jul 19, 2022 | Mar 11, 2027 | Sep 2, 2025 | 12 | United States, Brazil +6 |
| NCT07217184 | Sub-study of Belantamab Mafodotin (GSK2857916) in Combination With Isatuximab in Participants With RRMM | PHASE1 | ACTIVE NOT_RECRUITING | 30 | — | — | Jul 29, 2021 | Mar 11, 2027 | Oct 15, 2025 | 19 | United States, Australia +9 |
| NCT04808037 | Blmf, Lenalidomide and Dexamethasone in Transplant-ineligible Patients With Newly Diagnosed Multiple Myeloma | PHASE1 | ACTIVE NOT_RECRUITING | 66 | — | — | Feb 22, 2021 | Nov 8, 2028 | Oct 24, 2023 | 1 | Greece |
| NCT04398745 | A Study of Belantamab Mafodotin Monotherapy in Multiple Myeloma Participants With Normal and Varying Degree of Impaired Renal Function | PHASE1 | ACTIVE NOT_RECRUITING | 36 | — | — | Oct 9, 2020 | Dec 31, 2025 | May 23, 2025 | 19 | United States, Greece +2 |
| NCT07084896 | Sub-study of Belantamab Mafodotin (GSK2857916) in Combination With Nirogacestat in Participants With RRMM | PHASE1 | ACTIVE NOT_RECRUITING | 106 | — | — | Jun 8, 2020 | Mar 11, 2027 | May 6, 2026 | 29 | United States, Australia +11 |
| NCT04091126 | Study of Belantamab Mafodotin Plus Standard of Care (SoC) in Newly Diagnosed Multiple Myeloma | PHASE1 | ACTIVE NOT_RECRUITING | 118 | — | — | Dec 18, 2019 | Dec 31, 2026 | Nov 28, 2025 | 30 | United States, Australia +8 |
| NCT04177823 | A Study of Belantamab Mafodotin to Investigate Safety, Tolerability, Pharmacokinetics, Immunogenicity and Clinical Activity in Participants With Relapsed/Refractory Multiple Myeloma (RRMM) | PHASE1 | COMPLETED | 6 | — | — | Dec 9, 2019 | Dec 30, 2021 | Mar 20, 2025 | 1 | China |
| NCT07217119 | Sub-study of Belantamab Mafodotin (GSK2857916) in Combination With Feladilimab (GSK3359609) in Participants With RRMM | PHASE1 | ACTIVE NOT_RECRUITING | 25 | — | — | Nov 26, 2019 | Mar 11, 2027 | Oct 15, 2025 | 11 | United States, Australia +6 |
| NCT04126200 | Platform Study of Belantamab Mafodotin as Monotherapy and in Combination With Anti-cancer Treatments in Participants With Relapsed/Refractory Multiple Myeloma (RRMM) | PHASE1 | ACTIVE NOT_RECRUITING | 208 | — | — | Oct 7, 2019 | Mar 11, 2027 | May 6, 2026 | 38 | United States, Brazil +11 |
| NCT03848845 | Study Evaluating Safety, Tolerability and Clinical Activity of GSK2857916 in Combination With Pembrolizumab in Subjects With Relapsed/Refractory Multiple Myeloma (RRMM) | PHASE1 | COMPLETED | 41 | — | — | Mar 14, 2019 | Jun 14, 2023 | Apr 9, 2024 | 12 | United States, Canada +2 |
| NCT03828292 | An Open-label, Dose Escalation Study in Japanese Participants With Relapsed/Refractory Multiple Myeloma Who Have Failed Prior Anti Myeloma Treatments | PHASE1 | COMPLETED | 15 | — | — | Mar 14, 2019 | Sep 5, 2024 | Aug 19, 2025 | 4 | Japan |
| NCT03544281 | To Evaluate Safety, Tolerability, and Clinical Activity of the Antibody-drug Conjugate, GSK2857916 Administered in Combination With Lenalidomide Plus Dexamethasone (Arm A), or in Combination With Bortezomib Plus Dexamethasone (Arm B) in Participants With Relapsed/Refractory Multiple Myeloma (RRMM) | PHASE1 | COMPLETED | 153 | — | — | Sep 20, 2018 | Feb 28, 2024 | Mar 18, 2025 | 26 | United States, Australia +3 |
Defined as the time from the date of randomization to the date of first documented PD per International Myeloma Working Group (IMWG) criteria by Independent Review Committee (IRC) or death from any cause in the absence of progression, whichever occurs first.
Defined as achieving MRD negativity at 10\^-5 sensitivity threshold (1 nucleated tumor cell in 100,000 normal cells) assessed by next-generation sequencing (NGS) at least once during the time of confirmed complete response (CR) or better response per IMWG criteria by IRC.
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.
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.
KVA scale ranges from 0 to 4 with higher score indicating greater severity of corneal events.
KVA scale ranges from 0 to 4 with higher score indicating greater severity of corneal events.
KVA scale ranges from 0 to 4 with higher score indicating greater severity of corneal events. Data will be presented for the total number of participants with corneal events in each study group during 6 to 12 months.
ORR 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 \[CR\], stringent complete response \[sCR\]). Responses will be assessed using International Myeloma Working Group (IMWG) criteria.
The KVA scale is based on the evaluation of corneal changes using slit lamp examination. This scale provides a standardized approach for evaluating the relationship between corneal health and visual acuity. KVA scale is defined as Grade 0: No keratopathy, normal visual acuity with no corneal abnormalities; Grade 1: Mild changes to the cornea with no significant loss in visual acuity; Grade 2: Moderate corneal changes with noticeable visual acuity reduction; Grade 3: Severe corneal changes with substantial visual acuity impairment; Grade 4: Very severe corneal changes leading to significant vision loss. Higher grade indicates greater severity of corneal events.
ORR is defined as the percentage of participants with a confirmed Partial response (PR) or better as the best overall response (BOR), according to the International Myeloma Working Group (IMWG) Response Criteria.
Determination of the safety and tolerability of belantamab mafodotin in combination with lenalidomide and dexamethasone to establish a recommended Phase 2 dose for participants with newly diagnosed Multiple Myeloma, transplant-ineligible
Evaluation of the preliminary clinical activity of the Recommended Phase 2 Dose of belantamab mafodotin in combination with lenalidomide and dexamethasone for participants with newly diagnosed Multiple Myeloma, transplant-ineligible
Determine the safety and tolerability of blmf in combination with lenalidomide and dexamethasone to establish a recommended Phase 2 dose for participants with newly diagnosed Multiple Myeloma, transplant-ineligible
Further evaluation of the safety of Belantamab Mafodotin in combination with Lenalidomide and Dexamethasone
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Criteria for dose-limiting toxicity (DLT) included hematologic indicators such as Grade 3-5 febrile neutropenia and thrombocytopenia with bleeding. Non-hematologic criteria, excluding corneal toxicity, comprise Grade 3-5 toxicities, with exceptions for manageable nausea, vomiting, or diarrhea, controlled Grade 3 hypertension, and events linked to disease progression. Tumor lysis syndrome (TLS) of Grade 3 or 4, successfully managed within 7 days without end-organ damage, was considered. Corneal toxicity, assessed by the GSK corneal grading scale at Grade 4, is a DLT. Other organ-specific toxicities, notably liver toxicity meeting GSK stopping criteria, also qualified as DLTs. Severity was graded using National Cancer Institute (NCI) - Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.
Blood samples were collected for evaluation of hematology parameters including Anemia (An), Hemoglobin increased (HbI), Lymphocyte count decreased (LyD), Lymphocytes count increased (LyI), Neutrophils count decreased (NeuD), Platelet count decreased (PD), Leukocytosis (LC) and White blood cell decreased (WBCD). The laboratory parameters were graded according to CTCAE v5.0. 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. Any worst-case post baseline increases to G1, G2, G3, and G4 are presented. Baseline value was defined as the most recent, non-missing value from a local laboratory prior to the first dose of study treatment.
Blood samples were collected for evaluation of clinical chemistry parameters including Hypoglycemia (HG), Hypoalbuminemia (HA), Creatinine Kinase increased (CPKi), Hyperkalemia (HK), Blood lactate dehydrogenase Increased (BLDi), Hypermagnesemia (HyperM), Hypomagnesemia (HypoM), Hypernatremia (HyperN), Hypercalcemia (HyperC), Hypocalcemia (HypoC) and Chronic Kidney Disease (CKD). The laboratory parameters were graded according to CTCAE version 5. G1: mild; G2: moderate; 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. Any worst-case post baseline increase to G1, G2, G3, and G4 are presented. Baseline value was defined as the most recent, non-missing value from a local laboratory prior to the first dose of study treatment.
Overall Response Rate (ORR) was defined as the percentage of participants with a confirmed Partial Response (PR) or better as the best overall response (i.e., PR, Very Good Partial Response \[VGPR\], Complete Response \[CR\], and stringent Complete Response \[sCR\]), as assessed by the investigator per international myeloma working group (IMWG) (2016). PR is defined as ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to \<200 mg/24 h. VGPR is defined as 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 is defined as negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND \<5% plasmacytomas in the bone marrow. sCR is defined as CR as above PLUS normal serum free light-chain (FLC) assay ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence.
The number of participants with DLTs will be reported.
AEs and SAEs will be collected.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.
An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; important medical events that may jeopardize the participant or may require medical or surgical intervention; is associated with liver injury and impaired liver function.
An event was considered DLT if it occurred within 21 days of treatment and met any of the following criteria within same period: * Any Grade (Gr.) 3 or greater non-hematologic toxicity as described in NCI-CTCAE Version 5.0, other than corneal events that persists for \>48 hours despite supportive treatment or leads to hospitalization. * Hematologic toxicity such as Gr. 3 or greater febrile neutropenia lasting \>48 hours despite adequate treatment (Gr. 3 defined as absolute neutrophil count (ANC) \<1000/millimeter cube (mm\^3) at a single temperature \>38.3 degree celsius or a sustained temperature \>=38 degree celsius for more than 1 hour) and, Gr. 4 thrombocytopenia defined as platelet count \<25000/mm\^3 with clinically significant bleeding, or if platelet transfusion is required. * Gr. 4 per the corneal grading scale. * Liver toxicity meeting pre-specified by GSK liver stopping criteria.
Number of Participants who passed screening and were randomized across sub studies are presented.
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations which involve medical or scientific judgment or is associated with liver injury and impaired liver function.
DLT is an AE that is considered by the investigator to be clinically relevant and attributed to the study therapy during the 21 day DLT period and meets at least one of the DLT criteria: any Grade 4 and 3 non-hematologic toxicity, any Grade 3 or greater non-hematologic laboratory value, hematologic toxicity lasting \>=7 days, except Grade 4 thrombocytopenia of any duration or Grade 3 thrombocytopenia associated with clinically significant bleeding. Grade 3 or greater febrile neutropenia lasting \>48 hours (h) despite adequate treatment, Nephrotoxicity requiring dialysis, Liver toxicity, prolonged delay (\>14 days) in initiating Cycle 2 due to any treatment (pembrolizumab or GSK2857916) related toxicity, any treatment-related toxicity that causes discontinuation of treatment during Cycle 1, any other toxicity considered to be dose-limiting that occurs beyond 21 days and any other event which in the judgment of the investigator and GlaxoSmithKline Medical Monitor is considered to be a DLT.
Blood samples were collected for the analysis of following hematology parameters: hemoglobin, White blood cells (WBC) count, lymphocytes, neutrophils and platelet count. The laboratory parameters were graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Higher grade indicates greater severity and an increase in CTCAE grade was defined relative to the Baseline grade. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Any worst-case post baseline increase in grade along with any increase to a maximum grade of 3 and a maximum grade of 4 are presented.
Blood samples were collected for the analysis of following hematology parameters: basophils, eosinophils, mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), erythrocytes, hematocrit, monocytes, neutrophils and reticulocyte. The summaries of worst-case change from baseline with respect to normal range was analyzed for only those laboratory tests that were not gradable by CTCAE version 4.03. 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.
Blood samples were collected for the analysis of clinical chemistry parameters: glucose, alanine aminotransferase (ALT), albumin, alkaline phosphatase, aspartate aminotransferase (AST), blood bilirubin, calcium, creatine kinase (CPK), creatinine, gamma glutamyl transferase (GGT), magnesium, phosphate, potassium and sodium. Laboratory parameters were graded according to NCI-CTCAE version 4.03. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Higher grade indicates greater severity and an increase in CTCAE grade was defined relative to the Baseline grade. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Any worst case post baseline increase in grade along with any increase to a maximum grade of 3 and a maximum grade of 4 are presented.
Blood samples were collected for the analysis of following chemistry parameters: calcium, carbon dioxide, chloride, direct bilirubin, protein, thyrotropin (TSH), thyroxine (T4) and triiodothyronine (T3). The summaries of worst case change from baseline with respect to normal range was analyzed for only those laboratory tests that were not gradable by CTCAE version 4.03. 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.
Urine samples were collected to assess urine glucose, protein, occult blood and ketones using dipstick method. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters were recorded as negative, trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Result for urinalysis parameters were recorded as no change/decreased and any increase. Data for worst-case post baseline urinalysis results is presented.
Urine samples were collected from participants to assess urine pH levels. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date.
Urine samples were collected from participants to assess urine specific gravity. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date.
DBP and SBP were measured after resting for at least 5 minutes in a supine or semi-recumbent position. They were graded according to NCI-CTCAE version 4.03. For SBP: Grade 0 (\<=120 millimeter of mercury \[mmHg\]), Grade 1 (121-139 mmHg), Grade 2 (140-159 mmHg), Grade 3 (\>=160 mmHg). For DBP: Grade 0 (\<=80 mmHg), Grade 1 (81-89 mmHg), Grade 2 (90-99 mmHg), Grade 3 (\>=100 mmHg). Higher grade indicates greater severity. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst-case post baseline with any grade increase and a maximum post-baseline grade increase to Grade 3 from their baseline grade are presented.
Vital signs (pulse rate and temperature) were measured after resting for at least 5 minutes in a supine or semi-recumbent position. The abnormal vital sign ranges were: For pulse rate (low \<60 beats per minute \[bpm\] and high \>100 bpm); For body temperature (\<=35 degrees Celsius or \>=38 degrees Celsius). Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst case change from baseline was presented as Baseline to low, Baseline to Normal or No change and Baseline to High.
ORR was 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. 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; 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; PR = ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to \<200 mg/24 h.
DLT is an Adverse Event (AE) that is considered by the investigator to be clinically relevant and attributed to the study therapy during the 21-day DLT period and meets at least one of the DLT criteria: Grade 3 or greater febrile neutropenia lasting \>48 hours (h) despite adequate treatment, Grade 4 thrombocytopenia \<25,000/mm\^3accompanied by clinically significant bleeding, any Grade 3 or greater non-hematologic toxicity, any Grade 3 or greater non-hematologic laboratory value if: laboratory abnormality persists for \>48 h despite supportive treatment for abnormality leads to hospitalization, Grade 4 Corneal toxicity, and liver toxicity meeting pre-specified GlaxoSmithKline liver stopping criteria. DLTs were assessed by National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 4.03.
DLT is an AE that is considered by the investigator to be clinically relevant and attributed to the study therapy during the 21-day DLT period and meets at least one of the DLT criteria: Grade 3 or greater febrile neutropenia lasting \>48 hours (h) despite adequate treatment, Grade 4 thrombocytopenia \<25,000/mm\^3 accompanied by clinically significant bleeding, any Grade 3 or greater non-hematologic toxicity, any Grade 3 or greater non-hematologic laboratory value if: laboratory abnormality persists for \>48 h despite supportive treatment or abnormality leads to hospitalization, Grade 4 Corneal toxicity, and liver toxicity meeting pre-specified GlaxoSmithKline liver stopping criteria. DLTs were assessed by NCI-CTCAE, version 4.03.
DLT is an AE that is considered by the investigator to be clinically relevant and attributed to the study therapy during the 21-day DLT period and meets at least one of the DLT criteria: Grade 3 or greater febrile neutropenia lasting \>48 hours (h) despite adequate treatment, Grade 4 thrombocytopenia \<25,000/mm\^3 accompanied by clinically significant bleeding, any Grade 3 or greater non-hematologic toxicity, any Grade 3 or greater non-hematologic laboratory value if: laboratory abnormality persists for \>48 h despite supportive treatment or abnormality leads to hospitalization, Grade 4 Corneal toxicity, and liver toxicity meeting pre-specified GlaxoSmithKline liver stopping criteria. DLTs were assessed by NCI-CTCAE, version 4.03.
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death; was life threatening; required hospitalization or prolongation of existing hospitalization; resulted in disability/incapacity; was a congenital anomaly/birth defect. SAEs are subset of 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. SAE is defined as any untoward medical occurrence that, at any dose results in death, Is life-threatening, Requires inpatient hospitalization or prolongation of existing hospitalization, Results in persistent disability/incapacity or Is a congenital anomaly/birth defect other situations which involve medical or scientific judgment or is associated with liver injury and impaired liver function. SAEs are subset of AEs.
Blood samples were collected for clinical chemistry parameters analysis: Creatine Kinase (CK), Creatinine, Gamma Glutamyl Transferase (GGT), Magnesium, Phosphate, Potassium, Sodium, Calcium, Glucose, Urate, Alanine Aminotransferase (ALT), Albumin, Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Bilirubin were graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version (v) 4.03. Grade (G)1: mild; G2: moderate; G3: severe or medically significant; G4: life-threatening consequences. Higher grade indicates greater severity and increase in grade was defined relative to Baseline grade. Any worst-case post baseline increases in grade along with any increase to a maximum G3 and a maximum G4 are presented. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Blood samples were collected for analysis of clinical chemistry parameters: C Reactive Protein, Chloride, Direct Bilirubin (DB), Lactate Dehydrogenase, Protein and Urea. The summaries of worst-case change from baseline with respect to normal range was analyzed for only those laboratory tests that were not gradable by CTCAE v4.03. 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 was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Blood samples were collected for clinical chemistry parameters analysis: Creatine Kinase (CK), Creatinine, Gamma Glutamyl Transferase (GGT), Magnesium, Phosphate, Potassium, Sodium, Calcium, Glucose, Urate, Alanine Aminotransferase (ALT), Albumin, Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Bilirubin were graded according to NCI-CTCAE v 4.03. G1: mild; G2: moderate; G3: severe or medically significant; G4: life-threatening consequences. Higher grade indicates greater severity and increase in grade was defined relative to Baseline grade. Any worst-case post baseline increases in grade along with any increase to a maximum G3 and a maximum G4 are presented. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Blood samples were collected for analysis of clinical chemistry parameters: C Reactive Protein, Chloride, Direct Bilirubin (DB), Lactate Dehydrogenase, Protein and Urea. The summaries of worst-case change from baseline with respect to normal range was analyzed for only those laboratory tests that were not gradable by CTCAE v4.03. 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 was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Blood samples were collected for analysis of hematology parameters: Hemoglobin, Leukocytes, Lymphocytes, Neutrophils and Platelets were graded according to CTCAE v4.03. G1: mild; G2: moderate; G3: severe or medically significant; G4: life-threatening consequences. Higher grade indicates greater severity and increase in grade was defined relative to Baseline grade. Any worst-case post baseline increases in grade along with any increase to a maximum G3 and a maximum G4 are presented. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Blood samples were collected for the analysis of following hematology parameters: Basophils, Eosinophils, Mean Corpuscular Hemoglobin Concentration (MCHC), Mean Corpuscular Hemoglobin (MCH), Mean Corpuscular Volume (MCV), erythrocytes, Hematocrit, monocytes and reticulocytes. The summaries of worst-case change from baseline with respect to normal range was analyzed for only those laboratory tests that were not gradable by CTCAE version 4.03. 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 was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Blood samples were collected for analysis of hematology parameters: Hemoglobin, Leukocytes, Lymphocytes, Neutrophils and Platelets were graded according to CTCAE v4.03. G1: mild; G2: moderate; G3: severe or medically significant; G4: life-threatening consequences. Higher grade indicates greater severity and increase in grade was defined relative to Baseline grade. Any worst-case post baseline increases in grade along with any increase to a maximum G3 and a maximum G4 are presented. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Blood samples were collected for the analysis of following hematology parameters: Basophils, Eosinophils, MCHC, MCH, MCV, erythrocytes, Hematocrit, monocytes and reticulocytes. The summaries of worst-case change from baseline with respect to normal range was analyzed for only those laboratory tests that were not gradable by CTCAE version 4.03. The number of participants with decreases to low, changes to normal or no changes, and increases to high from baseline values have been presented. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Urine samples were collected to analyze presence of occult blood and protein in urine by dipstick method. Data for worst-case post baseline urinalysis results is presented. Result for urinalysis parameters were recorded as no change/decreased, Increase to SMALL, Increase to MODERATE, Increase to LARGE, and any increase including increase to +-, 1+, 2+, 3+, unknown indicating proportional concentrations in the urine sample.
Urine samples were collected to analyze presence of occult blood and protein in urine by dipstick method. Data for worst-case post baseline urinalysis results is presented. Result for urinalysis parameters were recorded as no change/decreased, Increase to SMALL, Increase to MODERATE, Increase to LARGE, and any increase including increase to +-, 1+, 2+, 3+, unknown indicating proportional concentrations in the urine sample.
Urine samples were collected to analyze urine pH levels. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Urine samples were collected to analyze urine pH levels. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Urine samples were collected to analyze urine specific gravity. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Urine samples were collected to analyze urine specific gravity. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
DBP and SBP were measured after resting for at least 5 minutes in a supine or semi-recumbent position. They were graded according to NCI-CTCAE version 4.03. For SBP: Grade (G) 0 (\<120 millimeter of mercury \[mmHg\]), G1 (120-139 mmHg), G2 (140-159 mmHg), G3 (\>=160 mmHg). For DBP: G0 (\<80 mmHg), G1 (80-89 mmHg), G2 (90-99 mmHg), G3 (\>=100 mmHg). Higher grade indicates greater severity. Data for participants with worst-case post baseline with any grade increase and a maximum post-baseline grade increase to G2 and G3 from their baseline grade are presented. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
DBP and SBP were measured after resting for at least 5 minutes in a supine or semi-recumbent position. They were graded according to NCI-CTCAE version 4.03. For SBP: Grade (G) 0 (\<120 millimeter of mercury \[mmHg\]), G1 (120-139 mmHg), G2 (140-159 mmHg), G3 (\>=160 mmHg). For DBP: G0 (\<80 mmHg), G1 (80-89 mmHg), G2 (90-99 mmHg), G3 (\>=100 mmHg). Higher grade indicates greater severity. Data for participants with worst-case post baseline with any grade increase and a maximum post-baseline grade increase to G2 and G3 from their baseline grade are presented. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Temperature was measured after resting for at least 5 minutes. The abnormal ranges for body temperature were (\<=35 degrees Celsius or \>=38 degrees Celsius). Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Temperature was measured after resting for at least 5 minutes. The abnormal ranges for body temperature were (\<=35 degrees Celsius or \>=38 degrees Celsius). Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Heart rate was measured after resting for at least 5 minutes. The abnormal ranges for heart rate were (low \<60 beats per minute \[bpm\] and high \>100 bpm). Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits. Data for participants with worst case change from baseline was presented as Baseline to low, Baseline to Normal or No change and Baseline to High.
Heart rate was measured after resting for at least 5 minutes. The abnormal ranges for heart rate were (low \<60 beats per minute \[bpm\] and high \>100 bpm). Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits. Data for participants with worst case change from baseline was presented as Baseline to low, Baseline to Normal or No change and Baseline to High.
12-lead electrocardiogram (ECG) was obtained using an automated ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QT interval corrected using Fridericia's formula (QTcF) intervals. Grade 0 (\<450 millisecond (msec)), Grade 1 (450-480 msec), Grade 2 (481-500 msec), and Grade 3 (≥501 msec). Higher grade indicates greater severity. Data for participants with worst-case post baseline with any grade increase and a post-baseline grade increase to G2 and G3 from their baseline grade are presented. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
12-lead electrocardiogram (ECG) was obtained using an automated ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QT interval corrected using Fridericia's formula (QTcF) intervals. Grade 0 (\<450 millisecond (msec)), Grade 1 (450-480 msec), Grade 2 (481-500 msec), and Grade 3 (≥501 msec). Higher grade indicates greater severity. Data for participants with worst-case post baseline with any grade increase and a post-baseline grade increase to G2 and G3 from their baseline grade are presented. Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
The number of participants with worst-case post baseline performance status have been presented as 0-5. Where, 0- Fully active; 1- Restricted in strenuous activity but able to carry out light work activities; 2- Capable of self-care but unable to carry out any work activities; 3- Capable of limited self care, confined to bed/chair more than 50% of waking hours; 4- Completely disabled; can't carry on any self care; totally confined to bed/chair and 5- Dead.Baseline was defined as the latest pre-dose assessment within 21 days prior to first dose with a non-missing value, including those from unscheduled visits.
Any change in ECOG Performance status that was clinically significant in the medical and scientific judgment of the investigator and not related to an underlying disease was reported.
DLT is an adverse event (AE) that is considered by the investigator to be clinically relevant and attributed to the study therapy during the 28 day DLT period and meets at least one of the DLT criteria: Grade 3 or greater febrile neutropenia lasting \>48 hours (h) despite adequate treatment; Grade 4 thrombocytopenia \<25,000/mm\^3 accompanied by significant bleeding; any Grade 3 or greater non-hematologic laboratory value (if laboratory abnormality persist \>48 h despite supportive treatment or abnormality leading to hospitalisation); non-hematologic toxicity which does not resolve with appropriate supportive treatment within 48 h, Grade 4 corneal adverse events; and other organ specific toxicities (liver toxicity that causes discontinuation of treatment).
DLT is an adverse event (AE) that is considered by the investigator to be clinically relevant and attributed to the study therapy during the 21 day DLT period and meets at least one of the DLT criteria: Grade 3 or greater febrile neutropenia lasting \>48 hours (h) despite adequate treatment; Grade 4 thrombocytopenia \<25,000/mm\^3 accompanied by significant bleeding; any Grade 3 or greater non-hematologic laboratory value (if laboratory abnormality persist \>48 h despite supportive treatment or abnormality leading to hospitalisation); non-hematologic toxicity which does not resolve with appropriate supportive treatment within 48 h, Grade 4 corneal adverse events; and other organ specific toxicities (liver toxicity that causes discontinuation of treatment).
12-lead electrocardiogram (ECGs) were obtained using an automated ECG machine that automatically calculated the QTcF intervals. QTc values are categorized into the clinical concern ranges which are specific to changes in QTc: 31-60 milliseconds (msec), and \>60 msec, and \>530msec. An increase is defined relative to Baseline. Baseline (Day 1) was defined as latest pre-dose assessment with non-missing value, including unscheduled visits. Data of number of participants with worst-case increase post baseline is presented.
Blood samples were collected for analysis of following hematology parameters: Hemoglobin (hemoglobin increased and anemia), Lymphocytes (lymphocyte count increased and lymphocyte count decreased), Neutrophils, Platelets and Leukocytes (leukocytosis and white blood cells decreased). The laboratory parameters were graded according to Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.03. Grade (G) 1: mild; G2: moderate; G3: severe or medically significant; G4: life-threatening consequences. Higher grade indicates greater severity and increase in grade was defined relative to Baseline grade. Baseline (Day 1) was defined as latest pre-dose assessment with non-missing value, including unscheduled visits. Any worst-case post baseline increases in grade along with any increase to a maximum G3 and a maximum G4 are presented.
Blood samples were collected for the analysis of following hematology parameters: basophils, eosinophils, hematocrit, mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), monocytes, erythrocytes and reticulocyte. The summaries of worst-case change from baseline with respect to normal range was analyzed for only those laboratory tests that were not gradable by CTCAE version 4.03. The number of participants with decreases to low from baseline, changes to normal or no changes from baseline, and increases to high values from baseline have been presented. Baseline (Day 1) was defined as latest pre-dose assessment with non-missing value, including unscheduled visits.
Blood samples were collected for analysis of following clinical chemistry parameters: Hyperglycemia, Hypoglycemia, Albumin, Alkaline Phosphatase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase, (AST), Bilirubin, Creatine Kinase (CK), Creatinine, Gamma Glutamyl Transferase (GGT), Hyperkalemia, Hypokalemia, Hypermagnesemia, Hypomagnesemia, Phosphate, Hypernatremia, Hyponatremia, Urate, Hypercalcemia and Hypocalcemia. Laboratory parameters were graded according to CTCAE v4.03. Grade (G) 1: mild; G2: moderate; G3: severe or medically significant; G4: life-threatening consequences. Higher grade indicates greater severity and increase in grade was defined relative to Baseline grade. Baseline (Day 1) was defined as latest pre-dose assessment with non-missing value, including unscheduled visits. Any worst-case post baseline increases in grade along with any increase to a maximum G3 and a maximum G4 are presented.
Blood samples were collected for analysis of following clinical chemistry parameters: Direct Bilirubin (DB), Calcium, Chloride, Carbon Dioxide (CO2), lactate dehydrogenase (LDH) and Protein. The summaries of worst-case change from baseline with respect to normal range was analyzed for only those laboratory tests that were not gradable by CTCAE version 4.03. The number of participants with decreases to low from baseline, changes to normal or no changes from baseline, and increases to high values from baseline have been presented. Baseline (Day 1) was defined as latest pre-dose assessment with non-missing value, including unscheduled visits.
Urine samples were collected to analyze presence of occult blood and protein in urine by dipstick method. Data for worst-case post baseline urinalysis results is presented. Result for urinalysis parameters were recorded as no change/decreased and increase to trace, 1+, 2+, 3+, \>3+ indicating proportional concentrations in the urine sample. Baseline (Day 1) was defined as latest pre-dose assessment with non-missing value, including unscheduled visits.
Urine samples were collected to analyze urine pH levels. Baseline (Day 1) was defined as latest pre-dose assessment with non-missing value, including unscheduled visits.
Urine samples were collected to analyze urine specific gravity using dipstick method. Baseline (Day 1) was defined as latest pre-dose assessment with a non-missing value, including unscheduled visits.
Blood pressures (DBP and SBP) were measured after resting for at least 5 minutes in a supine or semi-recumbent position. Baseline (Day 1) was defined as latest pre-dose assessment with a non-missing value, including unscheduled visits. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Pulse rate was measured after resting for at least 5 minutes in a supine or semi-recumbent position. Baseline (Day 1) was defined as latest pre-dose assessment with a non-missing value, including unscheduled visits. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Temperature was measured after resting for at least 5 minutes in a supine or semi-recumbent position. Baseline (Day 1) was defined as latest pre-dose assessment with a non-missing value, including unscheduled visits. Change from Baseline was calculated as post-dose visit value minus Baseline value.
ORR was 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. 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; 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; PR: \>=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by \>=90% or to \<200 mg/24 h. Confidence intervals were based on the exact method.
| Arm | Type | Description |
|---|---|---|
| Arm A: Belantamab Mafodotin + Lenalidomide + Dexamethasone | EXPERIMENTAL | Belantamab mafodotin, lenalidomide, and dexamethasone will be administered. Treatment will continue in both arms until progressive disease (PD), death, unacceptable toxicity, withdrawal of consent, or end of study, whichever occurs first. |
| Arm B: Daratumumab + Lenalidomide + Dexamethasone | ACTIVE_COMPARATOR | Daratumumab, lenalidomide, and dexamethasone will be administered. Treatment will continue in both arms until PD, death, unacceptable toxicity, withdrawal of consent, or end of study, whichever occurs first. |
| Belantamab mafodotin plus Pomalidomide and Dexamethasone | EXPERIMENTAL | - |
| Bortezomib plus Pomalidomide and Dexamethasone | ACTIVE_COMPARATOR | - |
| Belantamab mafodotin and Bortezomib plus Dexamethasone | EXPERIMENTAL | - |
| Daratumumab and Bortezomib plus Dexamethasone | ACTIVE_COMPARATOR | - |
| Arm A: Belantamab mafodotin plus Pomalidomide and Dexamethasone | EXPERIMENTAL | - |
| Arm B: Bortezomib plus Pomalidomide and Dexamethasone | ACTIVE_COMPARATOR | - |
| Belantamab mafodotin and Bortezomib plus Dexamethasone (Arm A) | EXPERIMENTAL | - |
| Daratumumab and Bortezomib plus Dexamethasone (Arm B) | ACTIVE_COMPARATOR | - |
| Participants receiving Belantamab mafodotin | EXPERIMENTAL | Participants will receive belantamab mafodotin single agent dose on Day 1 of Q3W |
| Participants receiving pom/dex | ACTIVE_COMPARATOR | Participants will receive pomalidomide daily on Days 1 to 21 of each 28-day cycle, with dexamethasone once weekly on Days 1, 8, 15 and 22. |
| Participants receiving Belantamab mafodotin dosing regimen 1 + Bortezomib + Dexamethasone | EXPERIMENTAL | Participants will receive dosing regimen 1 of Belantamab mafodotin in combination with Bortezomib and Dexamethasone |
| Participants receiving Belantamab mafodotin dosing regimen 2 + Bortezomib + Dexamethasone | EXPERIMENTAL | Participants will receive dosing regimen 2 of Belantamab mafodotin in combination with Bortezomib and Dexamethasone. |
| Participants receiving Belantamab mafodotin dosing regimen 3 + Bortezomib + Dexamethasone | EXPERIMENTAL | Participants will receive dosing regimen 3 of Belantamab mafodotin in combination with Bortezomib and Dexamethasone. |
| Belantamab mafodotin + Pomalidomide + Dexamethasone (BPd) | EXPERIMENTAL | - |
| Belantamab mafodotin + Bortezomib + Dexamethasone (BVd) | EXPERIMENTAL | - |
| Belantamab mafodotin + Carfilzomib + dexamethasone (BKd) | EXPERIMENTAL | - |
| Cohort 1: Participants receiving belantamab mafodotin at dose level (DL) 1 | EXPERIMENTAL | - |
| Cohort 2: Participants receiving belantamab mafodotin at DL 2 | EXPERIMENTAL | - |
| Cohort 3: Participants receiving belantamab mafodotin at DL 3 | EXPERIMENTAL | - |
| Cohort 4: Participants receiving belantamab mafodotin at DL 4 | EXPERIMENTAL | - |
| Cohort 5: Participants receiving belantamab mafodotin at DL4 with alternative dose modification | EXPERIMENTAL | - |
| Normal hepatic function | EXPERIMENTAL | - |
| Moderate hepatic impairment | EXPERIMENTAL | - |
| Belantamab mafodotin + Nirogacestat + Pomalidomide + Dexamethasone | EXPERIMENTAL | - |
| Belantamab mafodotin + Nirogacestat + Lenalidomide + Dexamethasone | EXPERIMENTAL | - |
| Belantamab mafodotin + Isatuximab | EXPERIMENTAL | - |
| Cohort 1, First Part | EXPERIMENTAL | 12 patients are anticipated to receive Belantamab Mafodotin 2.5 Q8W = 2.5 mg/kg on Day 1 of every other 28-day cycle, in combination with Lenalidomide and Dexamethasone |
| Cohort 2, First Part | EXPERIMENTAL | 12 patients are anticipated to receive Belantamab Mafodotin 1.9 Q8W = 1.9 mg/kg on Day 1 of every other 28-day cycle, in combination with Lenalidomide and Dexamethasone |
| Cohort 3, First Part | EXPERIMENTAL | 12 patients are anticipated to receive Belantamab Mafodotin 1.4 Q8W = 1.4 mg/kg on Day 1 of every other 28-day cycle, in combination with Lenalidomide and Dexamethasone |
| Group A, Second Part | EXPERIMENTAL | 15 patients are anticipated to receive Belantamab Mafodotin in the Recommended Phase 2 Dose, in combination with Lenalidomide and Dexamethasone. In this Arm the ocular toxicity will be graded according to the Dose Modification Guidelines for Corneal-Related Adverse Events Associated with belantamab mafodotin |
| Group B, Second Part | EXPERIMENTAL | 15 patients are anticipated to receive Belantamab Mafodotin in the Recommended Phase 2 Dose, in combination with Lenalidomide and Dexamethasone. In this Arm the ocular toxicity will be graded according to the Dose modification guidance based on visual acuity |
| Part 1: Participants with normal/mild impaired renal function | EXPERIMENTAL | Participants with normal or mildly impaired renal function (Normal: individual glomerular filtration rate \[iGFR\]: \>=90 milliliter per minute; Mild impairment: iGFR: 60-89 mL/min will be administered with belantamab mafodotin 2.5 mg/kg as an intravenous infusion over 30 minutes Q3W on Day 1 of every 21- day cycle until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, or end of study, whichever occurs first. |
| Part 1: Participants with severe renal impairment | EXPERIMENTAL | Participants with severely impaired renal function (iGFR: 15-29 mL/min) will be administered with belantamab mafodotin 2.5 mg/kg as an intravenous infusion over 30 minutes Q3W on Day 1 of every 21- day cycle until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, or end of study, whichever occurs first. |
| Part 2: Participants with ESRD (not on dialysis) | EXPERIMENTAL | Participants with ESRD (iGFR: \<15 mL/min) not on dialysis will be administered with belantamab mafodotin either 2.5 mg/kg or 1.9 mg/kg (or other adjusted dose) as an intravenous infusion over 30 minutes Q3W on Day 1 of every 21- day cycle until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, or end of study, whichever occurs first. In Part 2, the dose will be decided after evaluation of pharmacokinetic and safety data of Part 1. |
| Part 2: Participants with ESRD (on hemodialysis) | EXPERIMENTAL | Participants with ESRD (iGFR: \<15 mL/min) on hemodialysis will be administered with belantamab mafodotin either 2.5 mg/kg or 1.9 mg/kg (or other adjusted dose) as an intravenous infusion over 30 minutes Q3W on Day 1 of every 21-day cycle until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, or end of study, whichever occurs first. In Part 2, the dose will be decided after evaluation of pharmacokinetic and safety data of Part 1. |
| Belantamab mafodotin + Nirogacestat | EXPERIMENTAL | - |
| Cohort 1: belantamab mafodotin 1.9 mg/kg Q3/4W + VRd/Rd | EXPERIMENTAL | Participants will receive 1.9 milligram /kilogram (mg/kg) Q3W dose of belantamab mafodotin on Day 1 of every cycle for the first 8 cycles in combination with VRd and Q4W dose in combination with Rd from cycle 9 onwards. |
| Cohort 2: belantamab mafodotin 1.4 mg/kg Q6/8W + VRd/Rd | EXPERIMENTAL | Participants will receive 1.4 mg/kg Q6W dose of belantamab mafodotin on Day 1 of every other cycle for the first 8 cycles in combination with VRd and Q8W dose in combination with Rd from cycle 9 onwards. |
| Cohort 3: belantamab mafodotin 1.9 mg/kg Q6/8W + VRd/Rd | EXPERIMENTAL | Participants will receive 1.9 mg/kg Q6W dose of belantamab mafodotin on Day 1 of every other cycle for the first 8 cycles in combination with VRd and Q8W dose in combination with Rd from cycle 9 onwards. |
| Cohort 4: belantamab mafodotin 1.0 mg/kg Q3/4W + VRd/Rd | EXPERIMENTAL | Participants will receive 1.0 mg/kg Q3W dose of belantamab mafodotin on Day 1 of every cycle for the first 8 cycles in combination with VRd and Q4W dose in combination with Rd from cycle 9 onwards. |
| Cohort 5: belantamab mafodotin 1.4 mg/kg Q3/4W + VRd/Rd | EXPERIMENTAL | Participants will receive 1.4 mg/kg Q3W dose of belantamab mafodotin on Day 1 of every cycle for the first 8 cycles in combination with VRd and Q4W dose in combination with Rd from cycle 9 onwards. |
| Cohort 6: belantamab mafodotin 1.4mg/kg cycle 1, 1.0 mg/kg Q9/12W Cycle 4+VRd/Rd | EXPERIMENTAL | Based on emerging data from Cohort 2-5, participants will receive 1.4 mg/kg dose of belantamab mafodotin on Day 1 of cycle 1, followed by 1.0 mg/kg dose on Day 1 of every third cycle from cycle 4 onwards, in combination with VRd for the first 8 cycles and in combination with Rd from cycle 9 onwards. |
| Cohort 7: belantamab mafodotin 1.9 mg/kg Cycle 1, 1.4 mg/kg Q9/12W Cycle 4+VRd/Rd | EXPERIMENTAL | Based on emerging data from Cohort 2-5, participants will receive 1.9 mg/kg dose of belantamab mafodotin of cycle 1, followed by 1.4 mg/kg on Day 1 of every third cycle from cycle 4 in combination with VRd for the first 8 cycles and in combination with Rd from cycle 9 onwards. |
| Cohort 8a : belantamab mafodotin 1.9 mg/kg Cycle 1,4; 1.4 mg/kg Q9/12W from Cycle 7 +VRd/Rd | EXPERIMENTAL | Based on emerging data from Cohort 6-7, participants will receive 1.9 mg/kg dose of belantamab mafodotin on Day 1 of cycle 1 and cycle 4, followed by 1.4 mg/kg on Day 1 of every third cycle from cycle 7 onwards, in combination with VRd for the first 8 cycles and in combination with Rd from cycle 9 onwards. |
| Cohort 8b: belantamab mafodotin 1.4 mg/kg Cycle 1,3; 1.0 mg/kg Q9/12W from Cycle 6 +VRd/Rd | EXPERIMENTAL | Based on emerging data from Cohort 6-7, participants will receive 1.4 mg/kg IV dose of belantamab mafodotin on Day 1 of cycle 1 and cycle 3, then 1.0 mg/kg on Day 1 of every third cycle from cycle 6 in combination with VRd for the first 8 cycles and in combination with Rd from cycle 9 onwards. |
| Cohort 8c: belantamab mafodotin 1.0 mg/kg Cycle 1,5;1.0 mg/kg Q9/12W from Cycle 9 +VRd/Rd | EXPERIMENTAL | Based on emerging data from Cohort 6-7, participants will receive 1.0 mg/kg IV dose of belantamab mafodotin on Day 1 of cycle 1 and cycle 5, then 1.0 mg/kg on day 1 of every third cycle from cycle 9 in combination with VRd for the first 8 cycles and in combination with Rd from cycle 9 onwards. |
| Chinese participants with relapsed/refractory multiple myeloma | EXPERIMENTAL | Participants will be administered belantamab mafodotin 2.5 mg/kg or 3.4 mg/kg as an intravenous infusion on Day 1 of each 21-day cycle over 30 minutes. Participants will be treated until disease progression, intolerable toxicity, end of study or informed consent withdrawal. |
| Belantamab mafodotin + Feladilimab | EXPERIMENTAL | - |
| Belantamab mafodotin+GSK3174998 dose exploration (Sub-study 1) | EXPERIMENTAL | - |
| Belantamab mafodotin+feladilimab dose exploration (Sub-study 2) | EXPERIMENTAL | - |
| Belantamab mafodotin+nirogacestat dose exploration(Sub-study 3) | EXPERIMENTAL | - |
| Belantamab mafodotin+dostarlimab dose exploration(Sub-study 4) | EXPERIMENTAL | - |
| Belantamab mafodotin+isatuximab dose exploration (Sub-study 5) | EXPERIMENTAL | - |
| Belantamab mafodotin+ nirogacestat+ lenalidomide+ dexamethasone dose exploration (Sub-study 6) | EXPERIMENTAL | - |
| Belantamab mafodotin+ nirogacestat+ pomalidomide + dexamethasone dose exploration (Sub-study 7) | EXPERIMENTAL | - |
| Belantamab mafodotin monotherapy cohort expansion | ACTIVE_COMPARATOR | - |
| Belantamab mafodotin+GSK3174998 cohort expansion (Sub-study 1) | EXPERIMENTAL | - |
| Belantamab mafodotin+ feladilimab cohort expansion (Sub-study 2) | EXPERIMENTAL | - |
| Belantamab mafodotin+ nirogacestat cohort expansion (Sub-study 3) | EXPERIMENTAL | - |
| Belantamab mafodotin+ dostarlimab cohort expansion (Sub-study 4) | EXPERIMENTAL | - |
| Belantamab mafodotin+ isatuximab cohort expansion (Sub-study 5) | EXPERIMENTAL | - |
| Belantamab mafodotin+ nirogacestat+ lenalidomide+ dexamethasone cohort expansion (Sub-study 6) | EXPERIMENTAL | - |
| Belantamab mafodotin+ nirogacestat+ pomalidomide + dexamethasone cohort expansion (Sub-study 7) | EXPERIMENTAL | - |
| Part 1: Dose escalation | EXPERIMENTAL | Subjects will receive belantamab mafodotin at escalating doses of 2.5 milligrams per kilograms (mg/kg) and 3.4 mg/kg along with 200 mg pembrolizumab via intravenous (IV) infusion on Day 1 of each 21-day cycle to establish RP2D. There will be maximum of 35 cycles of combination treatment. |
| Part 2: Expansion cohort | EXPERIMENTAL | Subjects will receive belantamab mafodotin at RP2D along with 200 mg pembrolizumab via IV infusion on Day 1 of each 21-day cycle. There will be maximum of 35 cycles of combination treatment. |
| Part 1: Belantamab mafodotin Monotherapy | EXPERIMENTAL | - |
| Part 2: Arm A: Belantamab mafodotin+Bortezomib/Dexamethasone | EXPERIMENTAL | - |
| Part 2: Arm B: Belantamab mafodotin+Pomalidomide/Dexamethasone | EXPERIMENTAL | - |
| Arm A: Belantamab mafodotin+lenalidomide +dexamethasone | EXPERIMENTAL | Participants will receive SINGLE full dose of belantamab mafodotin as 2.5 mg/kg and 1.9 mg/kg on Day 1 of every 28-day cycle as a 30-60 min infusion. SPLIT: belantamab mafodotin will be administered in two equal divided doses, 2.5 mg/kg SPLIT dose of a 1.25 mg/kg dose on Day 1 and a 1.25 mg/kg dose on Day 8 of each 28-day cycle. STRETCH: belantamab mafodotin will be administered as 1.9 mg/kg dose on Day 1 of every alternate 28-day cycles (C1, C3, C5, C7 and so on.) Participants will also receive Lenalidomide 25 mg or 10 mg orally daily, on Days 1-21 of each 28 day cycle with Dexamethasone, 40 mg weekly per oral (PO)/intravenously (IV) on Days 1,8,15, \& 22 of each cycle. |
| Arm B: Belantamab mafodotin+bortezomib+dexamethasone | EXPERIMENTAL | Participants will receive SINGLE full dose of belantamab mafodotin as 3.4 mg/kg; 2.5 mg/kg; 1.9 mg/kg on Day 1 of each 21-day cycle. SPLIT: belantamab mafodotin will be administered in two equal divided doses: 3.4 mg/kg SPLIT as 1.7 mg/kg dose on Day 1 \& 1.7 mg/kg dose on Day 8; 2.5 mg/kg SPLIT dosing as 1.25 mg/kg dose on Day 1 \& 1.25 mg/kg dose on Day 8 of each 21-day cycle. STRETCH: belantamab mafodotin will be administered as single dose of 2.5 mg/kg on Day 1 of every alternate 21-day cycles (C1,C3,C5,C7 \& so on), 1.9 mg/kg administered on Day 1 of every alternate 21-day cycles (C1,C3,C5,C7 and so on). Step Down(S/D) STRETCH=belantamab mafodotin 2.5 mg/kg dose will be administered on Day 1 C1 followed by 1.9 mg/kg starting dose on Day1 of alternate 21-day cycles C3 onwards (C3,C5,C7, \& so on). Bortezomib will be administered at 1.3 mg/m\^2 SC/IV on Days 1,4,8, \& 11 of every 21-day cycle. Dex will be administered at 20 mg PO or IV on Days 1,2,4,5,8,9,11, \& 12 of every 21-day cycle. |
| Name | Type | Description |
|---|---|---|
| Belantamab mafodotin | DRUG | Belantamab mafodotin will be administered. |
| Lenalidomide | DRUG | Lenalidomide will be administered. |
| Dexamethasone | DRUG | Dexamethasone will be administered. |
| Daratumumab | DRUG | Daratumumab will be administered. |
| Pomalidomide | DRUG | Immunomodulatory drug (IMiD) will be administered. |
| Bortezomib | DRUG | Proteasome Inhibitor will be administered. |
| Pom/dex (Pomalidomide plus low dose Dexamethasone) | DRUG | Pomalidomide and Dexamethasone will be administered. |
| Carfilzomib | DRUG | Carfilzomib will be administered. |
| Nirogacestat | DRUG | Nirogacestat will be administered. |
| Isatuximab | DRUG | Isatuximab will be administered. |
| Feladilimab | DRUG | Feladilimab will be administered. |
| GSK3174998 | DRUG | GSK3174998 will be administered. |
| Dostarlimab | DRUG | Dostarlimab will be administered. |
| Pembrolizumab | DRUG | Pembrolizumab will be available as 100 mg/4 mL solution that should be stored under refrigeration at 2-8 degree Celsius. Pembrolizumab injection (solution) will be diluted prior to IV administration in 0.9% sodium chloride injection or 5% dextrose injection. |
Inclusion Criteria: 1. Is at least 18 or the legal age of consent in the jurisdiction in which the study is taking place, at the time of signing the informed consent. 2. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informe...