A Phase 1/2 interventional study of Belantamab mafodotin and Nirogacestat in Multiple Myeloma, sponsored by GlaxoSmithKline. Active, not recruiting at 29 sites in 13 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-05-06.
Sponsored by GlaxoSmithKline · Phase 1/2, Interventional, and Treatment
The primary purpose is to determine the safety and tolerability of belantamab mafodotin in combination with nirogacestat and to establish the recommended Phase 2 dose for combination treatment to explore in the cohort expansion (CE) phase in participants with RRMM. This study is a sub study of the Master protocol (NCT04126200).
3,632 studies on the registry are indexed under Multiple Myeloma; 744 are open to participants now.
This study's enrollment of 106 is above the median of 41 across 2,907 interventional studies indexed under Multiple Myeloma.
Browse Multiple Myeloma studies →GlaxoSmithKline is the lead sponsor of 3,562 studies on the registry; 117 are open to participants now.
Of its 258 completed or terminated interventional studies of FDA-regulated products, 232 (90%) have results posted.
Counted across the registry records on this site, refreshed daily.
Participant must be 18 years of age inclusive or older, at the time of signing the informed consent.
Exclusion Criteria:
Participants with current corneal epithelial disease except mild punctate keratopathy.
Drug: Belantamab mafodotin · Drug: Nirogacestat
Belantamab mafodotin will be administered.
Also known as: GSK2857916
Nirogacestat will be administered.
DE Phase: Number of Participants With Dose Limiting Toxicities (DLTs)
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.
Time frame: Up to 28 days
DE Phase: Number of Participants With Adverse Events (AEs)
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. AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) coding system.
Time frame: Up to approximately 253 weeks
DE Phase: Number of Participants With Worst-case Hematology Results by Maximum Grade Increase Post - Baseline Relative to Baseline
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.
Time frame: Baseline (Day 1) and up to approximately 253 weeks
DE Phase: Number of Participants With Worst-Case Chemistry Results by Maximum Grade Increase Post - Baseline Relative to Baseline
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.
Time frame: Baseline (Day 1) and up to approximately 253 weeks
CE Phase: Overall Response Rate (ORR)
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.
Time frame: Up to approximately 253 weeks
DE Phase: Overall Response Rate (ORR)
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.
Time frame: Up to approximately 253 weeks
CE Phase: Clinical Benefit Rate (CBR)
Clinical benefit rate was defined as the percentage of participants with a confirmed minimal response (MR) or better according to the IMWG Response Criteria. MR is defined as \>= 25% but \< 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%.
Time frame: Up to approximately 253 weeks
DE Phase: Number of Participants Achieving Stringent Complete Response (SCR), Complete Response (CR), Very Good Partial Response (VGPR) and Partial Response (PR)
Partial Response \[PR\], Very Good Partial Response \[VGPR\], Complete Response \[CR\], and stringent Complete Response \[sCR\] as assessed by the investigator per 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.
Time frame: Up to approximately 253 weeks
CE Phase: Number of Participants Achieving SCR, CR, VGPR and PR
Partial Response \[PR\], Very Good Partial Response \[VGPR\], Complete Response \[CR\], and stringent Complete Response \[sCR\] as assessed by the investigator per 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.
Time frame: Up to approximately 253 weeks
DE Phase: Plasma Concentrations of Belantamab Mafodotin Antibody-Drug Conjugate (ADC)
Blood samples were collected for PK analysis of belantamab mafodotin Antibody-Drug Conjugate (ADC). Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the Overall Number of Participants Analyzed field. 'Number Analyzed' signifies participants evaluable for the specified timepoints.
Time frame: PRE-DOSE(PD), END OF INFUSION (EOI), EOI+2 HOURS(H), EOI+ 24H on Day(D) 1 of Cycle (C) 1; ANYTIME on C1 D4, D8, D22, and D29 ; PD and EOI on D1 of C2, C4, C6, C9, C12; PD on D1 of C18 and C30; End of Treatment (approximately 157 weeks)
CE Phase: Plasma Concentrations of Belantamab Mafodotin Antibody-Drug Conjugate (ADC)
Blood samples were collected for PK analysis of belantamab mafodotin Antibody-Drug Conjugate (ADC).
Time frame: PRE-DOSE(PD), END OF INFUSION (EOI), EOI+2 HOURS(H), EOI+ 24H on Day(D) 1 of Cycle (C) 1; ANYTIME on C1 D4, D8, and D22 ; PD and EOI on D1 of C2, C4, C6, C9, C12; PD on D1 of C18; End of Treatment (approximately 157 weeks)
DE Phase: Plasma Concentration of Belantamab Mafodotin Total Antibody
Blood samples were collected for PK analysis of Belantamab mafodotin total antibody.
Time frame: PRE-DOSE(PD), END OF INFUSION (EOI), EOI+2 HOURS(H), EOI+ 24H on Day(D) 1 of Cycle (C) 1; ANYTIME on C1 D4, D8, D22, and D29; PD and EOI on D1 of C2, C4, C6, C9, C12; PD on D1 of C18 and C30; End of Treatment (approximately 157 weeks)
CE Phase: Plasma Concentration of Belantamab Mafodotin Plasma Total Antibody
Blood samples were collected for PK analysis of Belantamab mafodotin total antibody.
Time frame: PRE-DOSE(PD), END OF INFUSION (EOI), EOI+2 HOURS(H), EOI+ 24H on Day(D) 1 of Cycle (C) 1; ANYTIME on C1 D4, D8, and D22; PD and EOI on D1 of C2, C4, C6, C9, C12; PD on D1 of C18; End of Treatment (appoximately 157 weeks)
DE Phase: Plasma Concentrations of Belantamab Mafodotin Cys- Monomethyl Auristatin-F (Cys-mcMMAF)
Blood samples were collected for PK analysis of belantamab mafodotin cys- monomethyl auristatin-F (cys-mcMMAF).
Time frame: PRE-DOSE(PD), END OF INFUSION (EOI), EOI+2 HOURS(H), EOI+ 24H on Day(D) 1 of Cycle (C) 1; ANYTIME on C1 D4, D8, D22, and D29; PD and EOI on D1 of C2, C4, C6, C9, C12; PD on D1 of C18 and C30; End of Treatment (approximately 157 weeks)
CE Phase: Plasma Concentrations of Belantamab Mafodotin Cys- Monomethyl Auristatin-F (Cys-mcMMAF)
Blood samples were collected for PK analysis of belantamab mafodotin cys- monomethyl auristatin-F (cys-mcMMAF).
Time frame: PRE-DOSE(PD), END OF INFUSION (EOI), EOI+2 HOURS(H), EOI+ 24H on Day(D) 1 of Cycle (C) 1; ANYTIME on C1 D4, D8, D22 ; PD and EOI on D1 of C2, C4, C6, C9, C12; PD on D1 of C18; End of Treatment (approximately 157 weeks)
DE Phase: Plasma Concentration of Nirogacestat When Administered in Combination With Belantamab Mafodotin
Blood samples were collected for PK analysis of Nirogacestat when administered orally in combination with belantamab mafodotin.
Time frame: PRE-DOSE (PD), Post-dose 30 Minutes, 1H, 2H, and 4H on Cycle (C) 1 Day (D) -2; PRE-DOSE (PD), Post-dose 30 Minutes, 1H, 2H, 4H, 8H on C1D1; PD on C1D4 and D8 ; PD, Post-dose 30 Minutes, 1H, 2H, 4H, 8H on C2D1
CE Phase: Plasma Concentration of Nirogacestat When Administered in Combination With Belantamab Mafodotin
Blood samples were collected for PK analysis of Nirogacestat when administered orally in combination with belantamab mafodotin.
Time frame: PRE-DOSE (PD), Post-dose 30 Minutes, 1H, 2H, 4H, 8H on C1D1; PD on C1D4 and D8 ; PD, Post-dose 30 Minutes, 1H, 2H, 4H, 8H on C2D1
DE Phase: Number of Participants With Post-baseline Positive Anti-drug Antibodies (ADAs) Against Belantamab Mafodotin
Serum samples were 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.
Time frame: C2 D1, C4 D1, C6 D1, C9 D1, C12 D1, C18 D1, C30 D1, End of Treatment (approximately 157 weeks)
CE Phase: Number of Participants With Post-baseline Positive ADAs Against Belantamab Mafodotin
Serum samples were 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.
Time frame: C2 D1, C4 D1, C6 D1, C9 D1, C12 D1, C18 D1, End of Treatment (approximately 157 weeks)
DE Phase: Titer of ADAs Against Belantamab Mafodotin
Serum samples were collected for the analysis of the presence of ADAs using validated immunoassays. All samples were to be further tested in screening assay, and positive samples were further to be characterized for antibody titers.
Time frame: Up to approximately 157 weeks.
CE Phase: Titer of ADAs Against Belantamab Mafodotin
Serum samples were collected for the analysis of the presence of ADAs using validated immunoassays. All samples were further tested in screening assay, and positive samples were further characterized for antibody titers.
Time frame: C2 D1 and at End of Treatment (approximately 157 weeks)
DE Phase: Number of Participants With Adverse Events of Special Interest (AESI) for Belantamab Mafodotin
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Adverse Events of Special Interest (whether serious or non serious) were collected.
Time frame: Up to approximately 253 weeks
CE Phase: Number of Participants With Adverse Events of Special Interest (AESI) for Belantamab Mafodotin
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Adverse Events of Special Interest (whether serious or non serious) were collected.
Time frame: Up to approximately 253 weeks
DE Phase: Number of Participants With Any Corneal Event by Maximum Grade as Per CTCAE Grade
The corneal events were graded according to CTCAE version 5. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant. Grade 4: Life-threatening consequences; Grade 5: Death related to AE. Higher grade indicates greater severity and an increase in CTCAE grade was defined relative to the Baseline grade. Results are presented for number of participants with any corneal events by maximum grade as per CTCAE grade v5.0.
Time frame: Up to approximately 253 weeks
CE Phase: Number of Participants With Any Corneal Event by Maximum Grade as Per CTCAE Grade
The corneal events were graded according to CTCAE version 5. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant. Grade 4: Life-threatening consequences; Grade 5: Death related to AE. Higher grade indicates greater severity and an increase in CTCAE grade was defined relative to the Baseline grade. Results are presented for number of participants with any corneal events by maximum grade as per CTCAE grade v5.0.
Time frame: Up to approximately 253 weeks
CE Phase: Progression-free Survival (PFS)
PFS is defined as the time from randomization until the earliest date of confirmed progressive disease (PD) per IMWG, or death due to any cause.
Time frame: Up to approximately 253 weeks
CE Phase: Duration of Response (DoR)
DoR is defined as the time from first documented evidence or PR or better until progressive disease per IMWG or death due to progressive disease among participants who achieve confirmed partial response or better.
Time frame: Up to approximately 253 weeks
CE Phase: 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 a response (confirmed PR or better).
Time frame: Up to approximately 253 weeks
CE Phase: Overall Survival (OS)
OS is defined as the time from randomization until death due to any cause.
Time frame: Up to approximately 253 weeks
CE Phase: Number of Participants With AEs and SAEs
An adverse event (AE) is any untoward medical occurrence in a clinical study 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; 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 judged by physician, is associated with liver injury and impaired liver function. AEs and SAEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) coding system.
Time frame: Up to approximately 253 weeks
CE Phase: Number of Participants With AEs Leading to Discontinuation
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with AEs leading to discontinuation were evaluated.
Time frame: Up to approximately 253 weeks
CE Phase: Number of Participants With Adverse Events Leading to Dose Reduction or Delay
Number of participants with adverse events leading to dose reduction or delay were evaluated.
Time frame: Up to approximately 253 weeks
CE Phase: Number of Participants With Worst-case Hematology Results by Maximum Grade Increase Post - Baseline Relative to Baseline
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 version 5. 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.
Time frame: Baseline (Day 1) and up to approximately 253 weeks
CE Phase: Number of Participants With Worst-Case Chemistry Results by Maximum Grade Increase Post - Baseline Relative to Baseline
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.
Time frame: Baseline (Day 1) and up to approximately 253 weeks
This is a sub-study of the master study NCT04126200. The sub-study included two phases - Dose Escalation (DE) and Cohort Expansion (CE).
| Milestone | DE Phase: 0.95 mg/kg Belantamab Mafodotin + Nirogacestat | DE Phase: 1.9 mg/kg Belantamab Mafodotin+ Nirogacestat | DE Phase: 1.0 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W + Nirogacestat BID | CE Phase: 0.95mg/kg Belantamab Mafodotin Q3W + Nirogacestat | CE Phase: 2.5mg/kg Belantamab Mafodotin Q3W |
|---|---|---|---|---|---|---|---|
| Started | 10 | 4 | 10 | 10 | 1 | 34 | 37 |
| Dlt evaluable population | 8 | 3 | 6 | 7 | 1 | 28 | 36 |
| Safety population | 10 | 4 | 10 | 10 | 1 | 34 | 37 |
| Pharmacokinetic population | 10 | 4 | 10 | 10 | 1 | 34 | 37 |
| Completed | 8 | 4 | 6 | 8 | 0 | 24 | 24 |
| Not completed | 2 | 0 | 4 | 2 | 1 | 10 | 13 |
| Withdrew: Lost to follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Withdrew: Physician decision | 1 | 0 | 1 | 0 | 0 | 2 | 1 |
| Withdrew: Withdrawal by subject | 1 | 0 | 1 | 0 | 1 | 7 | 9 |
| Withdrew: Ongoing at the time of analysis | 0 | 0 | 2 | 2 | 0 | 1 | 2 |
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.
| Participants | DE Phase: 0.95 mg/kg Belantamab Mafodotin + Nirogacestat | DE Phase: 1.9 mg/kg Belantamab Mafodotin+ Nirogacestat | DE Phase: 1.0 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W + Nirogacestat BID |
|---|---|---|---|---|---|
| DE Phase: Number of Participants With Dose Limiting Toxicities (DLTs) | 1 | 2 | 0 | 0 | 0 |
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. AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) coding system.
| Participants | DE Phase: 0.95 mg/kg Belantamab Mafodotin + Nirogacestat | DE Phase: 1.9 mg/kg Belantamab Mafodotin+ Nirogacestat | DE Phase: 1.0 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W + Nirogacestat BID |
|---|---|---|---|---|---|
| DE Phase: Number of Participants With Adverse Events (AEs) | 10 | 4 | 10 | 10 | 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.
| Participants | DE Phase: 0.95 mg/kg Belantamab Mafodotin + Nirogacestat | DE Phase: 1.9 mg/kg Belantamab Mafodotin+ Nirogacestat | DE Phase: 1.0 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W + Nirogacestat BID |
|---|---|---|---|---|---|
| An, Increase to Grade 1 | 2 | 0 | 1 | 1 | 0 |
| An, Increase to Grade 2 | 2 | 1 | 1 | 3 | 0 |
| An, Increase to Grade 3 | 3 | 1 | 1 | 0 | 0 |
| An, Increase to Grade 4 | 0 | 0 | 0 | 0 | 0 |
| HbI, Increase to Grade 1 | 0 | 0 | 0 | 0 | 0 |
| HbI, Increase to Grade 2 | 0 | 0 | 0 | 0 | 0 |
| HbI, Increase to Grade 3 | 0 | 0 | 0 | 0 | 0 |
| HbI, Increase to Grade 4 | 0 | 0 | 0 | 0 | 0 |
| LyD, Increase to Grade 1 | 0 | 1 | 0 | 1 | 0 |
| LyD, Increase to Grade 2 | 2 | 0 | 4 | 1 | 0 |
| LyD, Increase to Grade 3 | 5 | 2 | 2 | 2 | 0 |
| LyD, Increase to Grade 4 | 1 | 0 | 1 | 0 | 0 |
| LyI, Increase to Grade 1 | 0 | 0 | 0 | 0 | 0 |
| LyI, Increase to Grade 2 | 0 | 0 | 2 | 1 | 0 |
| LyI, Increase to Grade 3 | 0 | 0 | 0 | 0 | 0 |
| LyI, Increase to Grade 4 | 0 | 0 | 0 | 0 | 0 |
| NeuD, Increase to Grade 1 | 3 | 0 | 3 | 1 | 0 |
| NeuD, Increase to Grade 2 | 2 | 0 | 1 | 1 | 1 |
| NeuD, Increase to Grade 3 | 1 | 0 | 0 | 1 | 0 |
| NeuD, Increase to Grade 4 | 0 | 0 | 0 | 0 | 0 |
| PD, Increase to Grade 1 | 1 | 0 | 1 | 3 | 0 |
| PD, Increase to Grade 2 | 2 | 2 | 2 | 2 | 1 |
| PD, Increase to Grade 3 | 2 | 0 | 1 | 2 | 0 |
| PD, Increase to Grade 4 | 1 | 2 | 0 | 1 | 0 |
| LC, Increase to Grade 1 | 1 | 0 | 0 | 0 | 0 |
| LC, Increase to Grade 2 | 0 | 0 | 0 | 0 | 0 |
| LC, Increase to Grade 3 | 0 | 0 | 0 | 0 | 0 |
| LC, Increase to Grade 4 | 0 | 0 | 0 | 0 | 0 |
| WBCD, Increase to Grade 1 | 1 | 1 | 2 | 0 | 0 |
| WBCD, Increase to Grade 2 | 5 | 0 | 3 | 2 | 0 |
| WBCD, Increase to Grade 3 | 1 | 0 | 0 | 0 | 0 |
| WBCD, Increase to Grade 4 | 0 | 0 | 0 | 0 | 0 |
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.
| Participants | DE Phase: 0.95 mg/kg Belantamab Mafodotin + Nirogacestat | DE Phase: 1.9 mg/kg Belantamab Mafodotin+ Nirogacestat | DE Phase: 1.0 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W + Nirogacestat BID |
|---|---|---|---|---|---|
| HG, Increase to Grade 1 | 2 | 0 | 1 | 1 | 0 |
| HG, Increase to Grade 2 | 0 | 0 | 1 | 0 | 0 |
| HG, Increase to Grade 3 | 0 | 0 | 0 | 0 | 0 |
| HG, Increase to Grade 4 | 0 | 0 | 0 | 0 | 0 |
| HA, Increase to Grade 1 | 0 | 0 | 1 | 0 | 0 |
| HA, Increase to Grade 2 | 1 | 2 | 1 | 0 | 0 |
| HA, Increase to Grade 3 | 1 | 0 | 0 | 0 | 0 |
| HA, Increase to Grade 4 | 0 | 0 | 0 | 0 | 0 |
| CPKi, Increase to Grade 1 | 3 | 1 | 1 | 3 | 1 |
| CPKi, Increase to Grade 2 | 2 | 0 | 0 | 0 | 0 |
| CPKi, Increase to Grade 3 | 0 | 0 | 0 | 0 | 0 |
| CPKi, Increase to Grade 4 | 0 | 0 | 0 | 0 | 0 |
| HK, Increase to Grade 1 | 0 | 0 | 1 | 0 | 0 |
| HK, Increase to Grade 2 | 1 | 0 | 0 | 0 | 0 |
| HK, Increase to Grade 3 | 0 | 0 | 0 | 0 | 0 |
| HK, Increase to Grade 4 | 1 | 0 | 0 | 0 | 0 |
| BLDi, Increase to Grade 1 | 3 | 3 | 5 | 8 | 1 |
| BLDi, Increase to Grade 2 | 0 | 0 | 0 | 0 | 0 |
| BLDi, Increase to Grade 3 | 0 | 0 | 0 | 0 | 0 |
| BLDi, Increase to Grade 4 | 0 | 0 | 0 | 0 | 0 |
| HyperM, Increase to Grade 1 | 1 | 0 | 1 | 1 | 0 |
| HyperM, Increase to Grade 2 | 0 | 0 | 0 | 0 | 0 |
| HyperM, Increase to Grade 3 | 0 | 0 | 0 | 0 | 0 |
| HyperM, Increase to Grade 4 | 0 | 0 | 0 | 0 | 0 |
| HypoM, Increase to Grade 1 | 2 | 1 | 1 | 1 | 0 |
| HypoM, Increase to Grade 2 | 0 | 0 | 0 | 0 | 0 |
| HypoM, Increase to Grade 3 | 0 | 0 | 0 | 0 | 0 |
| HypoM, Increase to Grade 4 | 0 | 0 | 0 | 0 | 0 |
| HyperN, Increase to Grade 1 | 0 | 0 | 0 | 2 | 0 |
| HyperN, Increase to Grade 2 | 0 | 0 | 0 | 0 | 0 |
| HyperN, Increase to Grade 3 | 0 | 0 | 0 | 0 | 0 |
| HyperN, Increase to Grade 4 | 0 | 0 | 0 | 0 | 0 |
| HyperC, Increase to Grade 1 | 0 | 0 | 1 | 1 | 0 |
| HyperC, Increase to Grade 2 | 0 | 0 | 0 | 0 | 0 |
| HyperC, Increase to Grade 3 | 0 | 0 | 0 | 0 | 0 |
| HyperC, Increase to Grade 4 | 0 | 0 | 0 | 0 | 0 |
| HypoC, Increase to Grade 1 | 1 | 0 | 4 | 6 | 1 |
| HypoC, Increase to Grade 2 | 1 | 0 | 0 | 0 | 0 |
| HypoC, Increase to Grade 3 | 0 | 0 | 0 | 0 | 0 |
| HypoC, Increase to Grade 4 | 0 | 0 | 0 | 0 | 0 |
| CKD, Increase to Grade 1 | 0 | 0 | 0 | 0 | 0 |
| CKD, Increase to Grade 2 | 4 | 1 | 0 | 1 | 0 |
| CKD, Increase to Grade 3 | 0 | 0 | 0 | 1 | 0 |
| CKD, Increase to Grade 4 | 0 | 1 | 0 | 0 | 0 |
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.
| Percentage of participants | CE Phase: 0.95mg/kg Belantamab Mafodotin Q3W + Nirogacestat | CE Phase: 2.5mg/kg Belantamab Mafodotin Q3W |
|---|---|---|
| CE Phase: Overall Response Rate (ORR) | 29 (15.1 to 47.5) | 38 (22.5 to 55.2) |
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.
| Percentage of participants | DE Phase: 0.95 mg/kg Belantamab Mafodotin + Nirogacestat | DE Phase: 1.9 mg/kg Belantamab Mafodotin+ Nirogacestat | DE Phase: 1.0 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W + Nirogacestat BID |
|---|---|---|---|---|---|
| DE Phase: Overall Response Rate (ORR) | 60 (26.2 to 87.8) | 0 (0.0 to 60.2) | 40 (12.2 to 73.8) | 50 (18.7 to 81.3) | 0 (0.0 to 97.5) |
Clinical benefit rate was defined as the percentage of participants with a confirmed minimal response (MR) or better according to the IMWG Response Criteria. MR is defined as \>= 25% but \< 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%.
| Percentage of participants | CE Phase: 0.95mg/kg Belantamab Mafodotin Q3W + Nirogacestat | CE Phase: 2.5mg/kg Belantamab Mafodotin Q3W |
|---|---|---|
| CE Phase: Clinical Benefit Rate (CBR) | 35 (19.7 to 53.5) | 49 (31.9 to 65.6) |
Partial Response \[PR\], Very Good Partial Response \[VGPR\], Complete Response \[CR\], and stringent Complete Response \[sCR\] as assessed by the investigator per 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.
| Count of participants | DE Phase: 0.95 mg/kg Belantamab Mafodotin + Nirogacestat | DE Phase: 1.9 mg/kg Belantamab Mafodotin+ Nirogacestat | DE Phase: 1.0 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W + Nirogacestat BID |
|---|---|---|---|---|---|
| Stringent Complete Response (sCR) | 0 | 0 | 0 | 1 | 0 |
| Complete Response (CR) | 0 | 0 | 0 | 0 | 0 |
| Very Good Partial Response (VGPR) | 3 | 0 | 0 | 1 | 0 |
| Partial Response (PR) | 3 | 0 | 4 | 3 | 0 |
Partial Response \[PR\], Very Good Partial Response \[VGPR\], Complete Response \[CR\], and stringent Complete Response \[sCR\] as assessed by the investigator per 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.
| Count of participants | CE Phase: 0.95mg/kg Belantamab Mafodotin Q3W + Nirogacestat | CE Phase: 2.5mg/kg Belantamab Mafodotin Q3W |
|---|---|---|
| Stringent Complete Response (sCR) | 0 | 2 |
| Complete Response (CR) | 1 | 1 |
| Very Good Partial Response (VGPR) | 5 | 5 |
| Partial Response (PR) | 4 | 6 |
Blood samples were collected for PK analysis of belantamab mafodotin Antibody-Drug Conjugate (ADC). Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the Overall Number of Participants Analyzed field. 'Number Analyzed' signifies participants evaluable for the specified timepoints.
| Nanogram/millilitre (ng/mL) | DE Phase: 0.95 mg/kg Belantamab Mafodotin + Nirogacestat | DE Phase: 1.9 mg/kg Belantamab Mafodotin+ Nirogacestat | DE Phase: 1.0 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W + Nirogacestat BID |
|---|---|---|---|---|---|
| CYCLE 1 DAY 1, PRE-DOSE | 0.0 (0 to 0) | 0.0 (0 to 0) | 0.0 (0 to 0) | 0.0 (0 to 0) | 0.0 (NA to NA) |
| CYCLE 1 DAY 1, END OF INFUSION | 15750.0 (12300 to 24200) | 55350.0 (30800 to 73900) | 21750.0 (11000 to 38300) | 33400.0 (16800 to 49400) | 27600.0 (NA to NA) |
| CYCLE 1 DAY 1, 2 HOURS | 16550.0 (11100 to 24100) | 50300.0 (26100 to 67500) | 21100.0 (11000 to 47200) | 29300.0 (17100 to 50700) | 26900.0 (NA to NA) |
| CYCLE 1 DAY 1, 24 HOURS | 9235.0 (6320 to 14500) | 27150.0 (16800 to 37500) | — | — | — |
| CYCLE 1 DAY 4, ANYTIME SAMPLE | 4680.0 (1720 to 9580) | 13000.0 (7800 to 17900) | 7370.0 (3580 to 13900) | 10000.0 (2400 to 23500) | 13300.0 (NA to NA) |
| CYCLE 1 DAY 8, ANYTIME SAMPLE | 2320.0 (1290 to 5080) | 5545.0 (3800 to 6760) | 3910.0 (1520 to 5930) | 4690.0 (1700 to 11100) | 4870.0 (NA to NA) |
| CYCLE 1 DAY 22, ANYTIME SAMPLE | — | — | — | 476.0 (0 to 952) | — |
| CYCLE 1 DAY 29, ANYTIME SAMPLE | — | — | 570.0 (0 to 1270) | 2350.0 (NA to NA) | — |
| CYCLE 2 DAY 1, PRE-DOSE | 0.0 (0 to 6520) | 1230.0 (525 to 1600) | 326.5 (0 to 1510) | 308.5 (0 to 1880) | 0.0 (NA to NA) |
| CYCLE 2 DAY 1, END OF INFUSION | 16900.0 (0 to 25800) | 47150.0 (27000 to 65900) | 23100.0 (14000 to 28600) | 30350.0 (20500 to 64700) | 31400.0 (NA to NA) |
| CYCLE 4 DAY 1, PRE-DOSE | 1380.0 (863 to 2980) | 1390.0 (NA to NA) | 0.0 (0 to 28900) | 287.5 (0 to 1150) | — |
| CYCLE 4 DAY 1, END OF INFUSION | 20300.0 (13600 to 26300) | 56600.0 (NA to NA) | 22450.0 (17700 to 27700) | 20050.0 (3440 to 32200) | — |
| CYCLE 6 DAY 1, PRE-DOSE | 2495.0 (1450 to 3570) | 1430.0 (NA to NA) | 0.0 (0 to 523) | 780.0 (0 to 1280) | — |
| CYCLE 6 DAY 1, END OF INFUSION | 20050.0 (14300 to 30600) | 55900.0 (NA to NA) | 24600.0 (20100 to 27700) | 22450.0 (16700 to 29000) | — |
| CYCLE 9 DAY 1, PRE-DOSE | 2810.0 (0 to 5190) | 1570.0 (NA to NA) | 0.0 (0 to 0) | 530.0 (507 to 553) | — |
| CYCLE 9 DAY 1, END OF INFUSION | 19100.0 (15900 to 30100) | 53200.0 (NA to NA) | 21550.0 (20300 to 22800) | 7950.0 (0 to 15900) | — |
| CYCLE 12 DAY 1, PRE-DOSE | 2225.0 (1160 to 4790) | 2510.0 (NA to NA) | — | 1010.0 (0 to 2020) | — |
| CYCLE 12 DAY 1, END OF INFUSION | 27000.0 (19400 to 31600) | 35000.0 (NA to NA) | — | 10735.0 (7670 to 13800) | — |
| CYCLE 18 DAY 1, PRE-DOSE | 1500.0 (NA to NA) | — | — | — | — |
| CYCLE 30 DAY 1, PRE-DOSE | 790.0 (NA to NA) | — | — | — | — |
| END OF TREATMENT (~157 weeks), | 570.0 (0 to 6240) | 1130.0 (0 to 4070) | 994.5 (0 to 2380) | 302.5 (0 to 1850) | 0.0 (NA to NA) |
Blood samples were collected for PK analysis of belantamab mafodotin Antibody-Drug Conjugate (ADC).
| ng/mL | CE Phase: 0.95mg/kg Belantamab Mafodotin Q3W + Nirogacestat | CE Phase: 2.5mg/kg Belantamab Mafodotin Q3W |
|---|---|---|
| CYCLE 1 DAY 1, PRE-DOSE | 0.0 (0 to 0) | 0.0 (0 to 40500) |
| CYCLE 1 DAY 1, END OF INFUSION | 19150.0 (0 to 40700) | 53800.0 (1800 to 91200) |
| CYCLE 1 DAY 1, 2 HOURS | 17400.0 (10500 to 53200) | 52900.0 (23300 to 87100) |
| CYCLE 1 DAY 1, 24 HOURS | 11300.0 (3000 to 26500) | 31400.0 (13000 to 65500) |
| CYCLE 1 DAY 4, ANYTIME SAMPLE | 6320.0 (552 to 16300) | 16700.0 (5480 to 41000) |
| CYCLE 1 DAY 8, ANYTIME SAMPLE | 2735.0 (0 to 5000) | 7990.0 (2890 to 16600) |
| CYCLE 1 DAY 22, ANYTIME SAMPLE | — | 2955.0 (1700 to 4130) |
| CYCLE 2 DAY 1, PRE-DOSE | 561.0 (0 to 17600) | 1860.0 (0 to 3540) |
| CYCLE 2 DAY 1, END OF INFUSION | 21400.0 (0 to 34900) | 50600.0 (15500 to 97300) |
| CYCLE 4 DAY 1, PRE-DOSE | 522.0 (0 to 3030) | 1840.0 (0 to 7460) |
| CYCLE 4 DAY 1, END OF INFUSION | 19050.0 (9300 to 40600) | 46500.0 (26700 to 94300) |
| CYCLE 6 DAY 1, PRE-DOSE | 0.0 (0 to 4950) | 1265.0 (0 to 33700) |
| CYCLE 6 DAY 1, END OF INFUSION | 18700.0 (7970 to 36000) | 40600.0 (1240 to 89700) |
| CYCLE 9 DAY 1, PRE-DOSE | 2590.0 (692 to 3570) | 2300.0 (0 to 22000) |
| CYCLE 9 DAY 1, END OF INFUSION | 22350.0 (19400 to 32200) | 30300.0 (11800 to 73000) |
| CYCLE 12 DAY 1, PRE-DOSE | 2920.0 (1010 to 4030) | 2140.0 (0 to 15100) |
| CYCLE 12 DAY 1, END OF INFUSION | 21500.0 (14200 to 37200) | 29750.0 (1350 to 39600) |
| CYCLE 18 DAY 1, PRE-DOSE | 2105.0 (933 to 4780) | 2330.0 (0 to 6690) |
| END OF TREATMENT (~157 weeks) | 857.0 (0 to 11900) | 1485.0 (0 to 8260) |
Blood samples were collected for PK analysis of Belantamab mafodotin total antibody.
| ng/mL | DE Phase: 0.95 mg/kg Belantamab Mafodotin + Nirogacestat | DE Phase: 1.9 mg/kg Belantamab Mafodotin+ Nirogacestat | DE Phase: 1.0 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W + Nirogacestat BID |
|---|---|---|---|---|---|
| CYCLE 1 DAY 1, PRE-DOSE | 0.0 (0 to 0) | 0.0 (0 to 0) | 0.0 (0 to 0) | 0.0 (0 to 2330) | 0.0 (NA to NA) |
| CYCLE 1 DAY 1, END OF INFUSION | 16500.0 (10100 to 26800) | 37750.0 (27800 to 43400) | 21300.0 (8730 to 32000) | 27850.0 (12700 to 46200) | 32500.0 (NA to NA) |
| CYCLE 1 DAY 1, 2 HOURS | 16900.0 (12800 to 26700) | 35450.0 (26800 to 43900) | 21800.0 (9260 to 28400) | 27250.0 (9940 to 50600) | 33800.0 (NA to NA) |
| CYCLE 1 DAY 1, 24 HOURS | 10950.0 (8130 to 18400) | 21300.0 (16600 to 26000) | — | — | — |
| CYCLE 1 DAY 4, ANYTIME SAMPLE | 6220.0 (3630 to 13200) | 13400.0 (10100 to 18400) | 8500.0 (5060 to 14100) | 13600.0 (3370 to 34600) | 18800.0 (NA to NA) |
| CYCLE 1 DAY 8, ANYTIME SAMPLE | 3565.0 (2280 to 8570) | 9320.0 (6930 to 9640) | 5335.0 (3620 to 7870) | 8300.0 (1470 to 16700) | 7210.0 (NA to NA) |
| CYCLE 1 DAY 22, ANYTIME SAMPLE | — | — | — | 1605.0 (1230 to 1980) | — |
| CYCLE 1 DAY 29, ANYTIME SAMPLE | — | — | 3030.0 (759 to 3070) | 7020.0 (NA to NA) | — |
| CYCLE 2 DAY 1, PRE-DOSE | 1700.0 (823 to 3490) | 2310.0 (1440 to 3120) | 1440.0 (0 to 6350) | 2060.0 (0 to 3830) | 1600.0 (NA to NA) |
| CYCLE 2 DAY 1, END OF INFUSION | 21250.0 (747 to 29400) | 32900.0 (24500 to 35600) | 25200.0 (13800 to 34700) | 26700.0 (14400 to 42800) | 25200.0 (NA to NA) |
| CYCLE 4 DAY 1, PRE-DOSE | 4860.0 (3180 to 9250) | 3730.0 (NA to NA) | 792.0 (0 to 1440) | 1898.5 (778 to 5610) | — |
| CYCLE 4 DAY 1, END OF INFUSION | 23200.0 (18200 to 33300) | 40200.0 (NA to NA) | 25300.0 (13100 to 33800) | 24550.0 (4240 to 39700) | — |
| CYCLE 6 DAY 1, PRE-DOSE | 8600.0 (4290 to 10200) | 3450.0 (NA to NA) | 1310.0 (0 to 1560) | 2115.0 (1320 to 5490) | — |
| CYCLE 6 DAY 1, END OF INFUSION | 27400.0 (20200 to 36800) | 35500.0 (NA to NA) | 20800.0 (15500 to 23500) | 21400.0 (14700 to 29700) | — |
| CYCLE 9 DAY 1, PRE-DOSE | 12200.0 (0 to 18100) | 4990.0 (NA to NA) | 373.0 (0 to 746) | 2220.0 (1180 to 3260) | — |
| CYCLE 9 DAY 1, END OF INFUSION | 33200.0 (15300 to 44800) | 48200.0 (NA to NA) | 19250.0 (18600 to 19900) | 10475.0 (1250 to 19700) | — |
| CYCLE 12 DAY 1, PRE-DOSE | 8765.0 (2780 to 17200) | 7560.0 (NA to NA) | — | 2958.5 (897 to 5020) | — |
| CYCLE 12 DAY 1, END OF INFUSION | 35600.0 (16100 to 48200) | 50500.0 (NA to NA) | — | 12335.0 (6870 to 17800) | — |
| CYCLE 18 DAY 1, PRE-DOSE | 2340.0 (NA to NA) | — | — | — | — |
| CYCLE 30 DAY 1, PRE-DOSE | 2370.0 (NA to NA) | — | — | — | — |
| END OF TREATMENT (~157 weeks) | 1890.0 (0 to 24300) | 2980.0 (0 to 9290) | 2390.0 (2030 to 4720) | 1285.0 (0 to 3170) | 0.0 (NA to NA) |
Blood samples were collected for PK analysis of Belantamab mafodotin total antibody.
| ng/mL | CE Phase: 0.95mg/kg Belantamab Mafodotin Q3W + Nirogacestat | CE Phase: 2.5mg/kg Belantamab Mafodotin Q3W |
|---|---|---|
| CYCLE 1 DAY 1, PRE-DOSE | 0.0 (0 to 5050) | 0.0 (0 to 4580) |
| CYCLE 1 DAY 1, END OF INFUSION | 17000.0 (0 to 36700) | 45150.0 (7000 to 81500) |
| CYCLE 1 DAY 1, 2 HOURS | 17000.0 (9690 to 41100) | 46800.0 (29800 to 75900) |
| CYCLE 1 DAY 1, 24 HOURS | 12050.0 (4060 to 27500) | 36200.0 (17100 to 73100) |
| CYCLE 1 DAY 4, ANYTIME SAMPLE | 8005.0 (750 to 22500) | 22050.0 (9900 to 39000) |
| CYCLE 1 DAY 8, ANYTIME SAMPLE | 3970.0 (0 to 14000) | 15150.0 (5590 to 30600) |
| CYCLE 1 DAY 22, ANYTIME SAMPLE | — | 10630.0 (4670 to 13800) |
| CYCLE 2 DAY 1, PRE-DOSE | 1760.0 (0 to 16700) | 5460.0 (0 to 25900) |
| CYCLE 2 DAY 1, END OF INFUSION | 21600.0 (0 to 38100) | 48400.0 (16500 to 93000) |
| CYCLE 4 DAY 1, PRE-DOSE | 1935.0 (0 to 15700) | 8090.0 (1080 to 26600) |
| CYCLE 4 DAY 1, END OF INFUSION | 20050.0 (7070 to 61500) | 46250.0 (22100 to 196000) |
| CYCLE 6 DAY 1, PRE-DOSE | 1110.0 (0 to 8320) | 3680.0 (629 to 44500) |
| CYCLE 6 DAY 1, END OF INFUSION | 20200.0 (9470 to 32500) | 37100.0 (2490 to 77300) |
| CYCLE 9 DAY 1, PRE-DOSE | 6550.0 (3800 to 13300) | 9030.0 (1060 to 60400) |
| CYCLE 9 DAY 1, END OF INFUSION | 29350.0 (16600 to 37100) | 29600.0 (14900 to 66300) |
| CYCLE 12 DAY 1, PRE-DOSE | 7910.0 (1550 to 16600) | 6915.0 (723 to 17700) |
| CYCLE 12 DAY 1, END OF INFUSION | 33700.0 (10500 to 38700) | 27950.0 (15100 to 47600) |
| CYCLE 18 DAY 1, PRE-DOSE | 6165.0 (4090 to 8820) | 6760.0 (914 to 42500) |
| END OF TREATMENT (~157 weeks) | 2570.0 (0 to 16200) | 4050.0 (1180 to 22100) |
Blood samples were collected for PK analysis of belantamab mafodotin cys- monomethyl auristatin-F (cys-mcMMAF).
| Picogram / millilitre (pg/mL) | DE Phase: 0.95 mg/kg Belantamab Mafodotin + Nirogacestat | DE Phase: 1.9 mg/kg Belantamab Mafodotin+ Nirogacestat | DE Phase: 1.0 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W + Nirogacestat BID |
|---|---|---|---|---|---|
| CYCLE 1 DAY 1, PRE-DOSE | 0.00 (0.0 to 0.0) | 0.00 (0.0 to 0.0) | 0.00 (0.0 to 0.0) | 0.00 (0.0 to 0.0) | 0.00 (NA to NA) |
| CYCLE 1 DAY 1, END OF INFUSION | 163.50 (99.4 to 338.0) | 175.00 (168.0 to 317.0) | 96.55 (68.2 to 190.0) | 165.50 (99.3 to 1040.0) | 155.00 (NA to NA) |
| CYCLE 1 DAY 1, 2 HOURS | 191.00 (119.0 to 351.0) | 322.00 (225.0 to 388.0) | 137.50 (86.9 to 270.0) | 299.00 (156.0 to 1150.0) | 113.00 (NA to NA) |
| CYCLE 1 DAY 1, 24 HOURS | 387.50 (196.0 to 855.0) | 1697.50 (675.0 to 2720.0) | — | — | — |
| CYCLE 1 DAY 4, ANYTIME SAMPLE | 232.00 (145.0 to 711.0) | 528.50 (393.0 to 909.0) | 144.00 (115.0 to 358.0) | 432.00 (202.0 to 2950.0) | 244.00 (NA to NA) |
| CYCLE 1 DAY 8, ANYTIME SAMPLE | 71.20 (0.0 to 122.0) | 177.00 (163.0 to 193.0) | 88.45 (63.3 to 137.0) | 132.00 (71.4 to 245.0) | — |
| CYCLE 1 DAY 22, ANYTIME SAMPLE | — | — | — | 0.00 (0.0 to 0.0) | — |
| CYCLE 1 DAY 29, ANYTIME SAMPLE | — | — | 0.00 (0.0 to 0.0) | 0.00 (NA to NA) | — |
| CYCLE 2 DAY 1, PRE-DOSE | 0.00 (0.0 to 122.0) | 0.00 (0.0 to 0.0) | 0.00 (0.0 to 0.0) | 0.00 (0.0 to 0.0) | 0.00 (NA to NA) |
| CYCLE 2 DAY 1, END OF INFUSION | 131.00 (0.0 to 330.0) | 291.50 (201.0 to 369.0) | 142.00 (0.0 to 152.0) | 231.50 (126.0 to 907.0) | 122.00 (NA to NA) |
| CYCLE 4 DAY 1, PRE-DOSE | 0.00 (0.0 to 0.0) | 0.00 (NA to NA) | 0.00 (0.0 to 0.0) | 0.00 (0.0 to 0.0) | — |
| CYCLE 4 DAY 1, END OF INFUSION | 190.00 (113.0 to 312.0) | 5620.00 (NA to NA) | 91.70 (0.0 to 121.0) | 88.00 (0.0 to 176.0) | — |
| CYCLE 6 DAY 1, PRE-DOSE | 0.00 (0.0 to 0.0) | 0.00 (NA to NA) | 0.00 (0.0 to 0.0) | 0.00 (0.0 to 0.0) | — |
| CYCLE 6 DAY 1, END OF INFUSION | 164.50 (84.2 to 301.0) | 226.00 (NA to NA) | 145.00 (81.0 to 171.0) | 133.50 (102.0 to 214.0) | — |
| CYCLE 9 DAY 1, PRE-DOSE | 0.00 (0.0 to 0.0) | 0.00 (NA to NA) | 0.00 (0.0 to 0.0) | 0.00 (0.0 to 0.0) | — |
| CYCLE 9 DAY 1, END OF INFUSION | 128.00 (113.0 to 223.0) | 243.00 (NA to NA) | 100.85 (90.7 to 111.0) | 55.50 (0.0 to 111.0) | — |
| CYCLE 12 DAY 1, PRE-DOSE | 0.00 (0.0 to 188.0) | 0.00 (NA to NA) | — | 0.00 (0.0 to 0.0) | — |
| CYCLE 12 DAY 1, END OF INFUSION | 166.00 (114.0 to 229.0) | 285.00 (NA to NA) | — | 100.50 (0.0 to 201.0) | — |
| CYCLE 18 DAY 1, PRE-DOSE | 0.00 (NA to NA) | — | — | — | — |
| CYCLE 30 DAY 1, PRE-DOSE | 0.00 (NA to NA) | — | — | — | — |
| END OF TREATMENT (~157 weeks) | 0.00 (0.0 to 74.6) | 0.00 (0.0 to 73.8) | 0.00 (0.0 to 0.0) | 0.00 (0.0 to 71.2) | 0.00 (NA to NA) |
Blood samples were collected for PK analysis of belantamab mafodotin cys- monomethyl auristatin-F (cys-mcMMAF).
| pg/mL | CE Phase: 0.95mg/kg Belantamab Mafodotin Q3W + Nirogacestat | CE Phase: 2.5mg/kg Belantamab Mafodotin Q3W |
|---|---|---|
| CYCLE 1 DAY 1, PRE-DOSE | 0.00 (0.0 to 0.0) | 0.00 (0.0 to 0.0) |
| CYCLE 1 DAY 1, END OF INFUSION | 143.00 (0.0 to 550.0) | 453.00 (0.0 to 1360.0) |
| CYCLE 1 DAY 1, 2 HOURS | 179.00 (69.3 to 675.0) | 513.00 (175.0 to 2590.0) |
| CYCLE 1 DAY 1, 24 HOURS | 291.00 (137.0 to 4960.0) | 778.00 (436.0 to 5970.0) |
| CYCLE 1 DAY 4, ANYTIME SAMPLE | 237.00 (98.5 to 1470.0) | 548.00 (235.0 to 2530.0) |
| CYCLE 1 DAY 8, ANYTIME SAMPLE | 61.20 (0.0 to 629.0) | 200.00 (81.9 to 548.0) |
| CYCLE 1 DAY 22, ANYTIME SAMPLE | 0.00 (NA to NA) | 0.00 (0.0 to 0.0) |
| CYCLE 2 DAY 1, PRE-DOSE | 0.00 (0.0 to 94.2) | 0.00 (0.0 to 55.0) |
| CYCLE 2 DAY 1, END OF INFUSION | 126.00 (0.0 to 698.0) | 329.00 (0.0 to 684.0) |
| CYCLE 4 DAY 1, PRE-DOSE | 0.00 (0.0 to 0.0) | 0.00 (0.0 to 0.0) |
| CYCLE 4 DAY 1, END OF INFUSION | 128.50 (0.0 to 293.0) | 351.50 (119.0 to 987.0) |
| CYCLE 6 DAY 1, PRE-DOSE | 0.00 (0.0 to 0.0) | 0.00 (0.0 to 115.0) |
| CYCLE 6 DAY 1, END OF INFUSION | 113.00 (54.4 to 199.0) | 213.00 (0.0 to 492.0) |
| CYCLE 9 DAY 1, PRE-DOSE | 0.00 (0.0 to 0.0) | 0.00 (0.0 to 0.0) |
| CYCLE 9 DAY 1, END OF INFUSION | 137.00 (59.6 to 179.0) | 172.00 (0.0 to 533.0) |
| CYCLE 12 DAY 1, PRE-DOSE | 0.00 (0.0 to 0.0) | 0.00 (0.0 to 52.5) |
| CYCLE 12 DAY 1, END OF INFUSION | 112.00 (71.1 to 210.0) | 261.00 (0.0 to 2120.0) |
| CYCLE 18 DAY 1, PRE-DOSE | 0.00 (0.0 to 0.0) | 0.00 (0.0 to 0.0) |
| END OF TREATMENT (~157 weeks) | 0.00 (0.0 to 276.0) | 0.00 (0.0 to 162.0) |
Blood samples were collected for PK analysis of Nirogacestat when administered orally in combination with belantamab mafodotin.
| ng/mL | DE Phase: 0.95 mg/kg Belantamab Mafodotin + Nirogacestat | DE Phase: 1.9 mg/kg Belantamab Mafodotin+ Nirogacestat | DE Phase: 1.0 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W + Nirogacestat BID |
|---|---|---|---|---|---|
| CYCLE 1 DAY -2, PRE-DOSE | — | — | 0.00 (0.0 to 0.0) | 0.00 (0.0 to 579.0) | 0.00 (NA to NA) |
| CYCLE 1 DAY -2, 30 MINUTES | — | — | 377.00 (0.0 to 769.0) | 251.50 (0.8 to 1270.0) | 272.00 (NA to NA) |
| CYCLE 1 DAY -2, 1 HOUR | — | — | 371.00 (4.3 to 804.0) | 343.50 (21.2 to 968.0) | 345.00 (NA to NA) |
| CYCLE 1 DAY -2, 2 HOURS | — | — | 307.00 (19.3 to 688.0) | 319.00 (124.0 to 1360.0) | 153.00 (NA to NA) |
| CYCLE 1 DAY -2, 4 HOURS | — | — | 168.00 (75.3 to 278.0) | 161.50 (67.1 to 611.0) | 52.30 (NA to NA) |
| CYCLE 1 DAY 1, PRE-DOSE | 0.00 (0.0 to 0.0) | 0.00 (0.0 to 0.0) | 98.55 (34.7 to 564.0) | 88.25 (41.3 to 1000.0) | — |
| CYCLE 1 DAY 1, 30 MINUTES | 244.00 (7.9 to 1560.0) | 348.00 (78.5 to 914.0) | 253.00 (NA to NA) | 670.00 (188.0 to 998.0) | 585.00 (NA to NA) |
| CYCLE 1 DAY 1, 1 HOUR | 306.50 (122.0 to 1680.0) | 490.00 (108.0 to 923.0) | 465.00 (NA to NA) | 651.00 (389.0 to 1240.0) | 547.00 (NA to NA) |
| CYCLE 1 DAY 1, 2 HOURS | 265.50 (126.0 to 1060.0) | 325.00 (252.0 to 369.0) | 726.00 (NA to NA) | 413.50 (217.0 to 1100.0) | 207.00 (NA to NA) |
| CYCLE 1 DAY 1, 4 HOURS | 110.00 (58.4 to 431.0) | 127.00 (50.6 to 149.0) | 366.00 (NA to NA) | 215.00 (103.0 to 625.0) | 113.00 (NA to NA) |
| CYCLE 1 DAY 1, 8 HOURS | 50.90 (32.7 to 254.0) | 74.80 (30.4 to 102.0) | — | — | — |
| CYCLE 1 DAY 4, PRE-DOSE | 176.00 (93.5 to 409.0) | 161.00 (72.3 to 309.0) | 152.00 (42.9 to 339.0) | 171.50 (80.0 to 1390.0) | 138.00 (NA to NA) |
| CYCLE 1 DAY 8, PRE-DOSE | 129.00 (60.5 to 490.0) | 379.50 (20.6 to 1070.0) | 174.50 (53.9 to 403.0) | 218.00 (144.0 to 1140.0) | 117.00 (NA to NA) |
| CYCLE 2 DAY 1, PRE-DOSE | 86.60 (38.3 to 761.0) | 63.73 (2.1 to 195.0) | 1.83 (0.0 to 149.0) | 54.30 (0.0 to 724.0) | 24.00 (NA to NA) |
| CYCLE 2 DAY 1, 30 MINUTES | 228.00 (37.3 to 1830.0) | 12.70 (6.2 to 789.0) | 122.00 (1.2 to 550.0) | 484.50 (58.7 to 1190.0) | 74.00 (NA to NA) |
| CYCLE 2 DAY 1, 1 HOUR | 253.00 (78.6 to 2260.0) | 186.50 (33.9 to 773.0) | 220.00 (13.6 to 726.0) | 422.00 (81.8 to 1330.0) | 171.00 (NA to NA) |
| CYCLE 2 DAY 1, 2 HOURS | 236.50 (102.0 to 1400.0) | 162.00 (54.9 to 704.0) | 274.00 (81.9 to 523.0) | 334.50 (119.0 to 472.0) | 124.00 (NA to NA) |
| CYCLE 2 DAY 1, 4 HOURS | 170.00 (64.5 to 941.0) | 357.00 (173.0 to 400.0) | 196.00 (48.0 to 426.0) | 179.50 (109.0 to 326.0) | 58.20 (NA to NA) |
| CYCLE 2 DAY 1, 8 HOURS | 109.50 (36.8 to 823.0) | 183.00 (58.6 to 203.0) | — | — | — |
Blood samples were collected for PK analysis of Nirogacestat when administered orally in combination with belantamab mafodotin.
| ng/mL | CE Phase: 0.95mg/kg Belantamab Mafodotin Q3W + Nirogacestat |
|---|---|
| CYCLE 1 DAY 1, PRE-DOSE | 0.00 (0.0 to 0.0) |
| CYCLE 1 DAY 1, 30 MINUTES | 146.00 (0.0 to 1510.0) |
| CYCLE 1 DAY 1, 1 HOUR | 487.00 (14.1 to 1570.0) |
| CYCLE 1 DAY 1, 2 HOURS | 353.00 (21.2 to 826.0) |
| CYCLE 1 DAY 1, 4 HOURS | 192.00 (0.6 to 774.0) |
| CYCLE 1 DAY 1, 8 HOURS | 87.80 (0.0 to 337.0) |
| CYCLE 1 DAY 4, PRE-DOSE | 231.00 (57.4 to 1220.0) |
| CYCLE 1 DAY 8, PRE-DOSE | 246.50 (62.1 to 988.0) |
| CYCLE 2 DAY 1, PRE-DOSE | 142.00 (0.0 to 557.0) |
| CYCLE 2 DAY 1, 30 MINUTES | 390.00 (33.5 to 1250.0) |
| CYCLE 2 DAY 1, 1 HOUR | 448.00 (39.8 to 1640.0) |
| CYCLE 2 DAY 1, 2 HOURS | 444.00 (153.0 to 1290.0) |
| CYCLE 2 DAY 1, 4 HOURS | 247.00 (84.8 to 881.0) |
| CYCLE 2 DAY 1, 8 HOURS | 154.00 (1.0 to 756.0) |
Serum samples were 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.
| Participants | DE Phase: 0.95 mg/kg Belantamab Mafodotin + Nirogacestat | DE Phase: 1.9 mg/kg Belantamab Mafodotin+ Nirogacestat | DE Phase: 1.0 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W + Nirogacestat BID |
|---|---|---|---|---|---|
| CYCLE 2 DAY 1 | 0 | 0 | 0 | 0 | 0 |
| CYCLE 4 DAY 1 | 0 | 0 | 0 | 0 | — |
| CYCLE 6 DAY 1 | 0 | 0 | 0 | 0 | — |
| CYCLE 9 DAY 1 | 0 | 0 | 0 | 0 | — |
| CYCLE 12 DAY 1 | 0 | 0 | — | 0 | — |
| CYCLE 18 DAY 1 | 0 | — | — | — | — |
| CYCLE 30 DAY 1 | 0 | — | — | — | — |
| END OF TREATMENT (~157 weeks) | 0 | 0 | 0 | 0 | 0 |
Serum samples were 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.
| Participants | CE Phase: 0.95mg/kg Belantamab Mafodotin Q3W + Nirogacestat | CE Phase: 2.5mg/kg Belantamab Mafodotin Q3W |
|---|---|---|
| CYCLE 2 DAY 1 | 0 | 1 |
| CYCLE 4 DAY 1 | 0 | 0 |
| CYCLE 6 DAY 1 | 0 | 0 |
| CYCLE 9 DAY 1 | 0 | 0 |
| CYCLE 12 DAY 1 | 0 | 0 |
| CYCLE 18 DAY 1 | 0 | 0 |
| END OF TREATMENT (~157 weeks) | 1 | 0 |
Serum samples were collected for the analysis of the presence of ADAs using validated immunoassays. All samples were to be further tested in screening assay, and positive samples were further to be characterized for antibody titers.
No measurements were reported for this outcome.
Serum samples were collected for the analysis of the presence of ADAs using validated immunoassays. All samples were further tested in screening assay, and positive samples were further characterized for antibody titers.
| Titer | CE Phase: 0.95mg/kg Belantamab Mafodotin Q3W + Nirogacestat | CE Phase: 2.5mg/kg Belantamab Mafodotin Q3W |
|---|---|---|
| Cycle 2 Day 1 | — | 100 (NA to NA) |
| End of Treatment (~157 weeks) | 400.0 (NA to NA) | — |
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Adverse Events of Special Interest (whether serious or non serious) were collected.
| Participants | DE Phase: 0.95 mg/kg Belantamab Mafodotin + Nirogacestat | DE Phase: 1.9 mg/kg Belantamab Mafodotin+ Nirogacestat | DE Phase: 1.0 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W + Nirogacestat BID |
|---|---|---|---|---|---|
| DE Phase: Number of Participants With Adverse Events of Special Interest (AESI) for Belantamab Mafodotin | 10 | 4 | 9 | 10 | 0 |
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Adverse Events of Special Interest (whether serious or non serious) were collected.
| Participants | CE Phase: 0.95mg/kg Belantamab Mafodotin Q3W + Nirogacestat | CE Phase: 2.5mg/kg Belantamab Mafodotin Q3W |
|---|---|---|
| CE Phase: Number of Participants With Adverse Events of Special Interest (AESI) for Belantamab Mafodotin | 28 | 31 |
The corneal events were graded according to CTCAE version 5. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant. Grade 4: Life-threatening consequences; Grade 5: Death related to AE. Higher grade indicates greater severity and an increase in CTCAE grade was defined relative to the Baseline grade. Results are presented for number of participants with any corneal events by maximum grade as per CTCAE grade v5.0.
| Participants | DE Phase: 0.95 mg/kg Belantamab Mafodotin + Nirogacestat | DE Phase: 1.9 mg/kg Belantamab Mafodotin+ Nirogacestat | DE Phase: 1.0 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W + Nirogacestat BID |
|---|---|---|---|---|---|
| Grade 1 | 1 | 1 | 2 | 2 | 0 |
| Grade 2 | 1 | 1 | 3 | 2 | 0 |
| Grade 3 | 3 | 0 | 0 | 0 | 0 |
| Grade 4 | 0 | 0 | 0 | 0 | 0 |
| Grade 5 | 0 | 0 | 0 | 0 | 0 |
The corneal events were graded according to CTCAE version 5. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant. Grade 4: Life-threatening consequences; Grade 5: Death related to AE. Higher grade indicates greater severity and an increase in CTCAE grade was defined relative to the Baseline grade. Results are presented for number of participants with any corneal events by maximum grade as per CTCAE grade v5.0.
| Participants | CE Phase: 0.95mg/kg Belantamab Mafodotin Q3W + Nirogacestat | CE Phase: 2.5mg/kg Belantamab Mafodotin Q3W |
|---|---|---|
| Grade 1 | 9 | 9 |
| Grade 2 | 3 | 5 |
| Grade 3 | 0 | 2 |
| Grade 4 | 0 | 0 |
| Grade 5 | 0 | 0 |
PFS is defined as the time from randomization until the earliest date of confirmed progressive disease (PD) per IMWG, or death due to any cause.
| Months | CE Phase: 0.95mg/kg Belantamab Mafodotin Q3W + Nirogacestat | CE Phase: 2.5mg/kg Belantamab Mafodotin Q3W |
|---|---|---|
| CE Phase: Progression-free Survival (PFS) | 3.5 (1.4 to 8.6) | 9.6 (4.2 to 20.2) |
DoR is defined as the time from first documented evidence or PR or better until progressive disease per IMWG or death due to progressive disease among participants who achieve confirmed partial response or better.
| Months | CE Phase: 0.95mg/kg Belantamab Mafodotin Q3W + Nirogacestat | CE Phase: 2.5mg/kg Belantamab Mafodotin Q3W |
|---|---|---|
| CE Phase: Duration of Response (DoR) | NA (4.2 to NA) | 22.2 (4.9 to NA) |
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 a response (confirmed PR or better).
| Months | CE Phase: 0.95mg/kg Belantamab Mafodotin Q3W + Nirogacestat | CE Phase: 2.5mg/kg Belantamab Mafodotin Q3W |
|---|---|---|
| CE Phase: Time to Response (TTR) | 1.1 (0.7 to 1.4) | 1.4 (0.7 to 2.1) |
OS is defined as the time from randomization until death due to any cause.
| Months | CE Phase: 0.95mg/kg Belantamab Mafodotin Q3W + Nirogacestat | CE Phase: 2.5mg/kg Belantamab Mafodotin Q3W |
|---|---|---|
| CE Phase: Overall Survival (OS) | NA (11.7 to NA) | NA (19.9 to NA) |
An adverse event (AE) is any untoward medical occurrence in a clinical study 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; 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 judged by physician, is associated with liver injury and impaired liver function. AEs and SAEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) coding system.
| Participants | CE Phase: 0.95mg/kg Belantamab Mafodotin Q3W + Nirogacestat | CE Phase: 2.5mg/kg Belantamab Mafodotin Q3W |
|---|---|---|
| AE | 34 | 35 |
| SAE | 16 | 13 |
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with AEs leading to discontinuation were evaluated.
| Participants | CE Phase: 0.95mg/kg Belantamab Mafodotin Q3W + Nirogacestat | CE Phase: 2.5mg/kg Belantamab Mafodotin Q3W |
|---|---|---|
| CE Phase: Number of Participants With AEs Leading to Discontinuation | 2 | 1 |
Number of participants with adverse events leading to dose reduction or delay were evaluated.
| Participants | CE Phase: 0.95mg/kg Belantamab Mafodotin Q3W + Nirogacestat | CE Phase: 2.5mg/kg Belantamab Mafodotin Q3W |
|---|---|---|
| CE Phase: Number of Participants With Adverse Events Leading to Dose Reduction or Delay | 20 | 12 |
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 version 5. 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.
| Participants | CE Phase: 0.95mg/kg Belantamab Mafodotin Q3W + Nirogacestat | CE Phase: 2.5mg/kg Belantamab Mafodotin Q3W |
|---|---|---|
| An, Increase to Grade 1 | 1 | 5 |
| An, Increase to Grade 2 | 6 | 10 |
| An, Increase to Grade 3 | 6 | 4 |
| An, Increase to Grade 4 | 0 | 0 |
| HbI, Increase to Grade 1 | 1 | 0 |
| HbI, Increase to Grade 2 | 0 | 2 |
| HbI, Increase to Grade 3 | 1 | 0 |
| HbI, Increase to Grade 4 | 0 | 0 |
| LyD, Increase to Grade 1 | 5 | 5 |
| LyD, Increase to Grade 2 | 8 | 7 |
| LyD, Increase to Grade 3 | 5 | 4 |
| LyD, Increase to Grade 4 | 2 | 0 |
| LyI, Increase to Grade 1 | 0 | 1 |
| LyI, Increase to Grade 2 | 3 | 6 |
| LyI, Increase to Grade 3 | 0 | 0 |
| LyI, Increase to Grade 4 | 0 | 0 |
| NeuD, Increase to Grade 1 | 2 | 1 |
| NeuD, Increase to Grade 2 | 5 | 11 |
| NeuD, Increase to Grade 3 | 3 | 4 |
| NeuD, Increase to Grade 4 | 2 | 2 |
| PD, Increase to Grade 1 | 12 | 15 |
| PD, Increase to Grade 2 | 4 | 6 |
| PD, Increase to Grade 3 | 5 | 9 |
| PD, Increase to Grade 4 | 3 | 2 |
| LC, Increase to Grade 1 | 0 | 1 |
| LC, Increase to Grade 2 | 0 | 0 |
| LC, Increase to Grade 3 | 0 | 0 |
| LC, Increase to Grade 4 | 0 | 0 |
| WBCD, Increase to Grade 1 | 8 | 8 |
| WBCD, Increase to Grade 2 | 2 | 9 |
| WBCD, Increase to Grade 3 | 2 | 2 |
| WBCD, Increase to Grade 4 | 1 | 0 |
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.
| Participants | CE Phase: 0.95mg/kg Belantamab Mafodotin Q3W + Nirogacestat | CE Phase: 2.5mg/kg Belantamab Mafodotin Q3W |
|---|---|---|
| HG, Increase to Grade 1 | 7 | 2 |
| HG, Increase to Grade 2 | 0 | 0 |
| HG, Increase to Grade 3 | 0 | 0 |
| HG, Increase to Grade 4 | 0 | 0 |
| HA, Increase to Grade 1 | 2 | 3 |
| HA, Increase to Grade 2 | 3 | 3 |
| HA, Increase to Grade 3 | 0 | 1 |
| HA, Increase to Grade 4 | 0 | 0 |
| CPKi, Increase to Grade 1 | 7 | 9 |
| CPKi, Increase to Grade 2 | 1 | 4 |
| CPKi, Increase to Grade 3 | 0 | 0 |
| CPKi, Increase to Grade 4 | 1 | 0 |
| HK, Increase to Grade 1 | 5 | 3 |
| HK, Increase to Grade 2 | 0 | 1 |
| HK, Increase to Grade 3 | 1 | 0 |
| HK, Increase to Grade 4 | 0 | 0 |
| BLDi, Increase to Grade 1 | 18 | 24 |
| BLDi, Increase to Grade 2 | 0 | 0 |
| BLDi, Increase to Grade 3 | 0 | 0 |
| BLDi, Increase to Grade 4 | 0 | 0 |
| HyperM, Increase to Grade 1 | 6 | 3 |
| HyperM, Increase to Grade 2 | 0 | 0 |
| HyperM, Increase to Grade 3 | 1 | 0 |
| HyperM, Increase to Grade 4 | 0 | 0 |
| HypoM, Increase to Grade 1 | 6 | 5 |
| HypoM, Increase to Grade 2 | 1 | 0 |
| HypoM, Increase to Grade 3 | 0 | 0 |
| HypoM, Increase to Grade 4 | 0 | 0 |
| HyperN, Increase to Grade 1 | 7 | 2 |
| HyperN, Increase to Grade 2 | 0 | 0 |
| HyperN, Increase to Grade 3 | 0 | 0 |
| HyperN, Increase to Grade 4 | 0 | 0 |
| HyperC, Increase to Grade 1 | 4 | 7 |
| HyperC, Increase to Grade 2 | 2 | 0 |
| HyperC, Increase to Grade 3 | 0 | 2 |
| HyperC, Increase to Grade 4 | 0 | 1 |
| HypoC, Increase to Grade 1 | 10 | 7 |
| HypoC, Increase to Grade 2 | 2 | 2 |
| HypoC, Increase to Grade 3 | 1 | 0 |
| HypoC, Increase to Grade 4 | 1 | 0 |
| CKD, Increase to Grade 1 | 0 | 0 |
| CKD, Increase to Grade 2 | 2 | 9 |
| CKD, Increase to Grade 3 | 6 | 1 |
| CKD, Increase to Grade 4 | 1 | 0 |
Collected over All cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 253 weeks.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| DE Phase: 0.95 mg/kg Belantamab Mafodotin + Nirogacestat | 7/10 (70%) | 8/10 (80%) | 10/10 (100%) |
| DE Phase: 1.9 mg/kg Belantamab Mafodotin+ Nirogacestat | 2/4 (50%) | 2/4 (50%) | 4/4 (100%) |
| DE Phase: 1.0 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | 3/10 (30%) | 3/10 (30%) | 10/10 (100%) |
| DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | 2/10 (20%) | 2/10 (20%) | 10/10 (100%) |
| DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W + Nirogacestat BID | 0/1 (0%) | 0/1 (0%) | 0/1 (0%) |
| CE Phase: 0.95mg/kg Belantamab Mafodotin Q3W + Nirogacestat | 13/34 (38.2%) | 16/34 (47.1%) | 27/34 (79.4%) |
| CE Phase: 2.5mg/kg Belantamab Mafodotin Q3W | 11/37 (29.7%) | 13/37 (35.1%) | 34/37 (91.9%) |
| Event | DE Phase: 0.95 mg/kg Belantamab Mafodotin + Nirogacestat | DE Phase: 1.9 mg/kg Belantamab Mafodotin+ Nirogacestat | DE Phase: 1.0 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W + Nirogacestat BID | CE Phase: 0.95mg/kg Belantamab Mafodotin Q3W + Nirogacestat | CE Phase: 2.5mg/kg Belantamab Mafodotin Q3W |
|---|---|---|---|---|---|---|---|
| Urinary tract infectionInfections and infestations | 0/10 | 1/4 | 0/10 | 0/10 | 0/1 | 1/34 | 0/37 |
| Infusion related reactionInjury, poisoning and procedural complications | 2/10 | 1/4 | 0/10 | 0/10 | 0/1 | 0/34 | 1/37 |
| Febrile neutropeniaBlood and lymphatic system disorders | 0/10 | 0/4 | 0/10 | 1/10 | 0/1 | 1/34 | 1/37 |
| Atrial fibrillationCardiac disorders | 1/10 | 0/4 | 0/10 | 0/10 | 0/1 | 0/34 | 0/37 |
| Cardiac arrestCardiac disorders | 1/10 | 0/4 | 0/10 | 0/10 | 0/1 | 0/34 | 0/37 |
| Retroperitoneal haematomaGastrointestinal disorders | 0/10 | 0/4 | 1/10 | 0/10 | 0/1 | 0/34 | 0/37 |
| Localised oedemaGeneral disorders | 1/10 | 0/4 | 0/10 | 0/10 | 0/1 | 0/34 | 0/37 |
| Multiple organ dysfunction syndromeGeneral disorders | 1/10 | 0/4 | 0/10 | 0/10 | 0/1 | 1/34 | 0/37 |
| Oedema peripheralGeneral disorders | 1/10 | 0/4 | 0/10 | 0/10 | 0/1 | 0/34 | 0/37 |
| Systemic inflammatory response syndromGeneral disorders | 1/10 | 0/4 | 0/10 | 0/10 | 0/1 | 0/34 | 0/37 |
| Event | DE Phase: 0.95 mg/kg Belantamab Mafodotin + Nirogacestat | DE Phase: 1.9 mg/kg Belantamab Mafodotin+ Nirogacestat | DE Phase: 1.0 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W + Nirogacestat BID | CE Phase: 0.95mg/kg Belantamab Mafodotin Q3W + Nirogacestat | CE Phase: 2.5mg/kg Belantamab Mafodotin Q3W |
|---|---|---|---|---|---|---|---|
| DiarrhoeaGastrointestinal disorders | 7/10 | 2/4 | 8/10 | 3/10 | 0/1 | 17/34 | 4/37 |
| ThrombocytopeniaBlood and lymphatic system disorders | 4/10 | 3/4 | 1/10 | 3/10 | 0/1 | 10/34 | 10/37 |
| HypophosphataemiaMetabolism and nutrition disorders | 7/10 | 3/4 | 5/10 | 5/10 | 0/1 | 11/34 | 3/37 |
| Dry eyeEye disorders | 3/10 | 2/4 | 4/10 | 3/10 | 0/1 | 7/34 | 13/37 |
| Vision blurredEye disorders | 3/10 | 2/4 | 3/10 | 4/10 | 0/1 | 8/34 | 14/37 |
| NauseaGastrointestinal disorders | 3/10 | 2/4 | 0/10 | 2/10 | 0/1 | 8/34 | 4/37 |
| Decreased appetiteMetabolism and nutrition disorders | 1/10 | 2/4 | 2/10 | 1/10 | 0/1 | 0/34 | 0/37 |
| HeadacheNervous system disorders | 2/10 | 2/4 | 1/10 | 1/10 | 0/1 | 2/34 | 2/37 |
| AnaemiaBlood and lymphatic system disorders | 4/10 | 1/4 | 1/10 | 2/10 | 0/1 | 5/34 | 9/37 |
| Eye irritationEye disorders | 3/10 | 0/4 | 4/10 | 3/10 | 0/1 | 6/34 | 10/37 |
| Age, Customized(Participants) | DE Phase: 0.95 mg/kg Belantamab Mafodotin + Nirogacestat | DE Phase: 1.9 mg/kg Belantamab Mafodotin+ Nirogacestat | DE Phase: 1.0 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W + Nirogacestat BID | CE Phase: 0.95mg/kg Belantamab Mafodotin Q3W + Nirogacestat | CE Phase: 2.5mg/kg Belantamab Mafodotin Q3W | Total |
|---|---|---|---|---|---|---|---|---|
| 18 years to >=75 years | 10 | 4 | 10 | 10 | 1 | 34 | 37 | 106 |
| Sex: Female, Male(Participants) | DE Phase: 0.95 mg/kg Belantamab Mafodotin + Nirogacestat | DE Phase: 1.9 mg/kg Belantamab Mafodotin+ Nirogacestat | DE Phase: 1.0 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W + Nirogacestat BID | CE Phase: 0.95mg/kg Belantamab Mafodotin Q3W + Nirogacestat | CE Phase: 2.5mg/kg Belantamab Mafodotin Q3W | Total |
|---|---|---|---|---|---|---|---|---|
| Female | 5 | 2 | 4 | 4 | 0 | 18 | 16 | 49 |
| Male | 5 | 2 | 6 | 6 | 1 | 16 | 21 | 57 |
| Race/Ethnicity, Customized(Participants) | DE Phase: 0.95 mg/kg Belantamab Mafodotin + Nirogacestat | DE Phase: 1.9 mg/kg Belantamab Mafodotin+ Nirogacestat | DE Phase: 1.0 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W/Q8W + Nirogacestat BID | DE Phase: 1.4 mg/kg Belantamab Mafodotin Q4W + Nirogacestat BID | CE Phase: 0.95mg/kg Belantamab Mafodotin Q3W + Nirogacestat | CE Phase: 2.5mg/kg Belantamab Mafodotin Q3W | Total |
|---|---|---|---|---|---|---|---|---|
| All other races | 10 | 4 | 10 | 10 | 1 | 34 | 36 | 105 |
| Missing race | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: No — GSK will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/About\_GSK\_Patient\_Level\_Data\_Sharing\_Final\_13July2023.pdf.
This study is active, not recruiting, as verified in Apr 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.