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NCT07084896 · REGISTRY CONDITION SEARCH

Sub-study of Belantamab Mafodotin (GSK2857916) in Combination With Nirogacestat in Participants With RRMM

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase
PHASE1, PHASE2
Status at capture
ACTIVE NOT RECRUITING
Registry last update
2026-05-06

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).

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

DE Phase: Number of Participants With Dose Limiting Toxicities (DLTs)

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outcome · POSTED

DE Phase: Number of Participants With Adverse Events (AEs)

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outcome · POSTED

DE Phase: Number of Participants With Worst-case Hematology Results by Maximum Grade Increase Post - Baseline Relative to Baseline

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outcome · POSTED

DE Phase: Number of Participants With Worst-Case Chemistry Results by Maximum Grade Increase Post - Baseline Relative to Baseline

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outcome · POSTED

CE Phase: Overall Response Rate (ORR)

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outcome · POSTED

DE Phase: Overall Response Rate (ORR)

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outcome · POSTED

CE Phase: Clinical Benefit Rate (CBR)

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outcome · POSTED

DE Phase: Number of Participants Achieving Stringent Complete Response (SCR), Complete Response (CR), Very Good Partial Response (VGPR) and Partial Response (PR)

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outcome · POSTED

CE Phase: Number of Participants Achieving SCR, CR, VGPR and PR

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outcome · POSTED

DE Phase: Plasma Concentrations of Belantamab Mafodotin Antibody-Drug Conjugate (ADC)

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outcome · POSTED

CE Phase: Plasma Concentrations of Belantamab Mafodotin Antibody-Drug Conjugate (ADC)

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outcome · POSTED

DE Phase: Plasma Concentration of Belantamab Mafodotin Total Antibody

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outcome · POSTED

CE Phase: Plasma Concentration of Belantamab Mafodotin Plasma Total Antibody

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outcome · POSTED

DE Phase: Plasma Concentrations of Belantamab Mafodotin Cys- Monomethyl Auristatin-F (Cys-mcMMAF)

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outcome · POSTED

CE Phase: Plasma Concentrations of Belantamab Mafodotin Cys- Monomethyl Auristatin-F (Cys-mcMMAF)

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outcome · POSTED

DE Phase: Plasma Concentration of Nirogacestat When Administered in Combination With Belantamab Mafodotin

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outcome · POSTED

CE Phase: Plasma Concentration of Nirogacestat When Administered in Combination With Belantamab Mafodotin

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outcome · POSTED

DE Phase: Number of Participants With Post-baseline Positive Anti-drug Antibodies (ADAs) Against Belantamab Mafodotin

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outcome · POSTED

CE Phase: Number of Participants With Post-baseline Positive ADAs Against Belantamab Mafodotin

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outcome · POSTED

DE Phase: Titer of ADAs Against Belantamab Mafodotin

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outcome · POSTED

CE Phase: Titer of ADAs Against Belantamab Mafodotin

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outcome · POSTED

DE Phase: Number of Participants With Adverse Events of Special Interest (AESI) for Belantamab Mafodotin

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outcome · POSTED

CE Phase: Number of Participants With Adverse Events of Special Interest (AESI) for Belantamab Mafodotin

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outcome · POSTED

DE Phase: Number of Participants With Any Corneal Event by Maximum Grade as Per CTCAE Grade

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outcome · POSTED

CE Phase: Number of Participants With Any Corneal Event by Maximum Grade as Per CTCAE Grade

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outcome · POSTED

CE Phase: Progression-free Survival (PFS)

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outcome · POSTED

CE Phase: Duration of Response (DoR)

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outcome · POSTED

CE Phase: Time to Response (TTR)

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outcome · POSTED

CE Phase: Overall Survival (OS)

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outcome · POSTED

CE Phase: Number of Participants With AEs and SAEs

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outcome · POSTED

CE Phase: Number of Participants With AEs Leading to Discontinuation

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outcome · POSTED

CE Phase: Number of Participants With Adverse Events Leading to Dose Reduction or Delay

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outcome · POSTED

CE Phase: Number of Participants With Worst-case Hematology Results by Maximum Grade Increase Post - Baseline Relative to Baseline

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outcome · POSTED

CE Phase: Number of Participants With Worst-Case Chemistry Results by Maximum Grade Increase Post - Baseline Relative to Baseline

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
Inclusion Criteria: Participant must be 18 years of age inclusive or older, at the time of signing the informed consent. * Participants must have histologically or cytologically confirmed diagnosis of Multiple Myeloma (MM), as defined by the IMWG. * Participants having at least 3 prior lines of prior anti-myeloma treatments including an immunomodulating agent (IMID) a proteasome inhibitor (PI) and an anti-CD38 monoclonal antibody. * Participants with a history of autologous stem cell transplant are eligible for study participation when, transplant was \>100 days prior to study enrolment and with no active infection(s). * Participants with Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, unless ECOG less than equal to (\<=)2 is due solely to skeletal complications and/or skeletal pain due to MM. * Participants with measurable disease defined as at least one of the following: Serum M-protein greater than equal to (\>=)0.5 gram per deciliter (\>=5 gram per liter) or Urine M-protein \>=200 milligrams (mg) per 24 hours or Serum free light chain (FLC) assay: Involved FLC level \>=10 mg per deciliter (\>=100 mg per Liter) and an abnormal serum FLC ratio (\<0.26 or \>1.65). * Participants who have tested positive for Hepatitis B core antibody (HBcAb) can be enrolled if the following criteria are met: Serology result HBcAb+, Hepatitis B surface antigen (HBsAg)-; HBV deoxyribonucleic acid (DNA) undetectable during screening. * Participants who are currently receiving physiological doses oral steroids (\<10 mg/day), inhaled steroids or ophthalmological steroids. Exclusion Criteria: Participants with current corneal epithelial disease except mild punctate keratopathy. * Participants with evidence of cardiovascular risk. * Participants with known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to belantamab mafodotin or any of the components of the study treatment. History of severe hypersensitivity to other mAb. * Participants with active infection requiring antibiotic, antiviral, or antifungal treatment. * Participants with other monoclonal antibodies within 30 days or systemic anti-myeloma therapy within \<14 days. * Participants with prior radiotherapy within 2 weeks of start of study therapy. * Participants with prior allogeneic transplant are prohibited. * Participants who have received prior Chimeric Antigen T cell therapy (CAR-T) therapy with lymphodepletion with chemotherapy within 3 months of screening. * Participants with any major surgery (other than bone-stabilizing surgery) within the last 30 days. * Participants with prior treatment with an investigational agent within 14 days or 5 half-lives of receiving the first dose of study drugs, whichever is shorter. * Participants with \>=grade 3 toxicity considered related to prior check-point inhibitors and that led to treatment discontinuation. * Participants who have received transfusion of blood products within 2 weeks before the first dose of study drug. * Participants must not receive live attenuated vaccines within 30 days prior to first dose of study treatment or whilst receiving belantamab mafodotin +- partner agent in any sub-study arm of the platform trial and for at least 70 days following last study treatment. * Participants with presence of active renal condition (infection, requirement for dialysis or any other condition that could affect participant's safety). Participants with isolated proteinuria resulting from MM. * Participants with known human immunodeficiency virus (HIV) infection, unless the participant can meet all criteria: a) established anti-retroviral therapy for at least 4 weeks and HIV viral load\<400 copies/milliliter (mL) b) cluster of differentiation 4 plus (CD4+) T-cell (CD4+) counts \>= 350 cells/microliter (µL) c) No history of Acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections within the last 12 months in which case the participant would be eligible for CE Phase only. * Participants with uncontrolled small and/or large intestinal disease. * Participants with uncontrolled skin disease. * Participants with any condition causing hypophosphatemia, hypokalemia or hypomagnesemia which is refractory to electrolyte replacement. * Participants with previous administration of a gamma secretase inhibitor. * Participants with concomitant administration of a strong CYP3A4 inhibitor or inducer.
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. intervention Names
    1. Drug: Belantamab mafodotin
    2. Drug: Nirogacestat
    label
    Belantamab mafodotin + Nirogacestat
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Belantamab mafodotin + Nirogacestat
    description
    Belantamab mafodotin will be administered.
    name
    Belantamab mafodotin
    other Names
    1. GSK2857916
    type
    DRUG
  2. arm Group Labels
    1. Belantamab mafodotin + Nirogacestat
    description
    Nirogacestat will be administered.
    name
    Nirogacestat
    type
    DRUG
Study design
allocation
NA
intervention Model
SINGLE_GROUP
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
106
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    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.
    measure
    DE Phase: Number of Participants With Dose Limiting Toxicities (DLTs)
    time Frame
    Up to 28 days
  2. description
    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.
    measure
    DE Phase: Number of Participants With Adverse Events (AEs)
    time Frame
    Up to approximately 253 weeks
  3. description
    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.
    measure
    DE Phase: Number of Participants With Worst-case Hematology Results by Maximum Grade Increase Post - Baseline Relative to Baseline
    time Frame
    Baseline (Day 1) and up to approximately 253 weeks
  4. description
    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.
    measure
    DE Phase: Number of Participants With Worst-Case Chemistry Results by Maximum Grade Increase Post - Baseline Relative to Baseline
    time Frame
    Baseline (Day 1) and up to approximately 253 weeks
  5. description
    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.
    measure
    CE Phase: Overall Response Rate (ORR)
    time Frame
    Up to approximately 253 weeks
secondary Outcomes
  1. description
    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.
    measure
    DE Phase: Overall Response Rate (ORR)
    time Frame
    Up to approximately 253 weeks
  2. description
    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%.
    measure
    CE Phase: Clinical Benefit Rate (CBR)
    time Frame
    Up to approximately 253 weeks
  3. description
    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.
    measure
    DE Phase: Number of Participants Achieving Stringent Complete Response (SCR), Complete Response (CR), Very Good Partial Response (VGPR) and Partial Response (PR)
    time Frame
    Up to approximately 253 weeks
  4. description
    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.
    measure
    CE Phase: Number of Participants Achieving SCR, CR, VGPR and PR
    time Frame
    Up to approximately 253 weeks
  5. description
    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.
    measure
    DE Phase: Plasma Concentrations 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, 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)
  6. description
    Blood samples were collected for PK analysis of belantamab mafodotin Antibody-Drug Conjugate (ADC).
    measure
    CE Phase: Plasma Concentrations 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)
  7. description
    Blood samples were collected for PK analysis of Belantamab mafodotin total antibody.
    measure
    DE Phase: Plasma Concentration 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)
  8. description
    Blood samples were collected for PK analysis of Belantamab mafodotin total antibody.
    measure
    CE Phase: Plasma Concentration of Belantamab Mafodotin Plasma 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)
  9. description
    Blood samples were collected for PK analysis of belantamab mafodotin cys- monomethyl auristatin-F (cys-mcMMAF).
    measure
    DE Phase: Plasma Concentrations 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)
  10. description
    Blood samples were collected for PK analysis of belantamab mafodotin cys- monomethyl auristatin-F (cys-mcMMAF).
    measure
    CE Phase: Plasma Concentrations 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)
  11. description
    Blood samples were collected for PK analysis of Nirogacestat when administered orally in combination with belantamab mafodotin.
    measure
    DE Phase: Plasma Concentration of Nirogacestat When Administered 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
  12. description
    Blood samples were collected for PK analysis of Nirogacestat when administered orally in combination with belantamab mafodotin.
    measure
    CE Phase: Plasma Concentration of Nirogacestat When Administered 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
Full study description
brief Summary
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).
Source references
Source notices and limitations
    Discovery and provenance
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    Preserved source evidence · Not medical advice