Multiple MyelomaPhase 1/2NCT07084896
Sub-study of Belantamab Mafodotin (GSK2857916) in Combination With Nirogacestat in Participants With RRMM
A Phase 1/2 study testing Belantamab mafodotin and Nirogacestat in people with Multiple Myeloma, run by GlaxoSmithKline at 29 sites in 13 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Belantamab mafodotin and Nirogacestat
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 106 participants
- Where
- 29 sitesin 13 countries
- Study dates
- 8 Jun 2020to 11 Mar 2027
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 20Show fewer
- 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.
Trial locations and contacts
29 sites in 13 countries.
29 sites in 13 countries
United States4 sites
238995
Atlanta, Georgia, 30322
240593
Boston, Massachusetts, 02215
251164
Grand Rapids, Michigan, 49546
239015
Madison, Wisconsin, 53792
South Korea4 sites
GSK Investigational Site
Incheon, 21565
GSK Investigational Site
Seoul, 06351
GSK Investigational Site
Seoul, 06591
GSK Investigational Site
Ulsan, 44033
Spain4 sites
GSK Investigational Site
Badalona, 08916
GSK Investigational Site
Madrid, 28041
GSK Investigational Site
Madrid, 31008
GSK Investigational Site
Pozuelo de AlarcOn Madr, 28223
Germany3 sites
GSK Investigational Site
Frankfurt, 60590
GSK Investigational Site
Kiel, 24105
GSK Investigational Site
Leipzig, 04103
Poland3 sites
GSK Investigational Site
Katowice, 40-519
GSK Investigational Site
Lodz, 93-513
GSK Investigational Site
Lublin, 20-081
Canada2 sites
GSK Investigational Site
Halifax, Nova Scotia, B3H 1V7
GSK Investigational Site
Vancouver, British Columbia, V5Z1M9
France2 sites
GSK Investigational Site
Lille, 59037
GSK Investigational Site
Villejuif, 94805
Sweden2 sites
GSK Investigational Site
Falun, SE-791 82
GSK Investigational Site
Stockholm, SE-141 86
About this study
Official title: A Phase I/II, Randomized, Open-label Platform Study Utilizing a Master Protocol to Study Belantamab Mafodotin (GSK2857916) as Monotherapy and in Combination With Anti-Cancer Treatments in Participants With Relapsed/Refractory Multiple Myeloma (RRMM)-DREAMM5 - Sub-study 3 - Belantamab Mafodotin and Nirogacestat in Combination
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).
- Conditions
- Multiple Myeloma
- Being tested
- Belantamab mafodotin, Nirogacestat
- Keywords
- Belantamab Mafodotin, Nirogacestat, GSK2857916, Multiple myeloma
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Belantamab mafodotinDrug
Also called GSK2857916
Belantamab mafodotin will be administered.
NirogacestatDrug
Nirogacestat will be administered.
| Study group | Role | What they receive |
|---|---|---|
| Belantamab mafodotin + Nirogacestat | Experimental | Not described Receives: Drug: Belantamab mafodotin; Drug: Nirogacestat |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to approximately 253 weeks
Secondary outcomes (29)
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.
Measured: 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%.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: Up to approximately 253 weeks
CE Phase: Overall Survival (OS)
OS is defined as the time from randomization until death due to any cause.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline (Day 1) and up to approximately 253 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2025
- Study start8 Jun 2020
- Primary completion17 Apr 2025
- Study completion11 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 106 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07084896
- Sponsor's protocol ID
- 208887 Sub Study 3
- Other IDs
- 2023-509550-55, 2023
- Status last verified
- Apr 2026
- First submitted
- 22 Jul 2025
- Last updated
- 6 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- 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.
- Expanded access
- Available
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II, Randomized, Open-label Platform Study Utilizing a Master Protocol to Study Belantamab Mafodotin (GSK2857916) as Monotherapy and in Combination With Anti-Cancer Treatments in Participants With Relapsed/Refractory Multiple Myeloma (RRMM)-DREAMM5 - Sub-study 3 - Belantamab Mafodotin and Nirogacestat in Combination
- ClinicalTrials.gov ID
- NCT07084896
- Acronym / sponsor ID
- 208887 Sub Study 3
- Conditions
- Multiple Myeloma
- Keywords
- Belantamab Mafodotin, Nirogacestat, GSK2857916, Multiple myeloma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 106 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 8 Jun 2020 (actual)
- Primary completion
- 17 Apr 2025 (actual)
- Study completion
- 11 Mar 2027 (estimated)
- First posted
- 25 Jul 2025 (actual)
- Results
- Posted 6 May 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Belantamab mafodotin + Nirogacestat | Experimental | Drug: Belantamab mafodotin, Drug: Nirogacestat |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Belantamab mafodotinAlso: GSK2857916Belantamab mafodotin will be administered. | Drug | Belantamab mafodotin + Nirogacestat |
| NirogacestatNirogacestat will be administered. | Drug | Belantamab mafodotin + Nirogacestat |
Primary outcome
DE Phase: Number of Participants With Dose Limiting Toxicities (DLTs)
Time frame: Up to 28 days
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.
DE Phase: Number of Participants With Adverse Events (AEs)
Time frame: Up to approximately 253 weeks
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.
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
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.
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
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.
CE Phase: Overall Response Rate (ORR)
Time frame: Up to approximately 253 weeks
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.
29 secondary outcomes
DE Phase: Overall Response Rate (ORR)
Time frame: Up to approximately 253 weeks
CE Phase: Clinical Benefit Rate (CBR)
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)
Time frame: Up to approximately 253 weeks
CE Phase: Number of Participants Achieving SCR, CR, VGPR and PR
Time frame: Up to approximately 253 weeks
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)
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)
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)
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)
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)
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)
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
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
DE Phase: Number of Participants With Post-baseline Positive Anti-drug Antibodies (ADAs) Against Belantamab Mafodotin
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
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
Time frame: Up to approximately 157 weeks.
CE Phase: Titer of ADAs Against Belantamab Mafodotin
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
Time frame: Up to approximately 253 weeks
CE Phase: Number of Participants With Adverse Events of Special Interest (AESI) for Belantamab Mafodotin
Time frame: Up to approximately 253 weeks
DE Phase: Number of Participants With Any Corneal Event by Maximum Grade as Per CTCAE Grade
Time frame: Up to approximately 253 weeks
CE Phase: Number of Participants With Any Corneal Event by Maximum Grade as Per CTCAE Grade
Time frame: Up to approximately 253 weeks
CE Phase: Progression-free Survival (PFS)
Time frame: Up to approximately 253 weeks
CE Phase: Duration of Response (DoR)
Time frame: Up to approximately 253 weeks
CE Phase: Time to Response (TTR)
Time frame: Up to approximately 253 weeks
CE Phase: Overall Survival (OS)
Time frame: Up to approximately 253 weeks
CE Phase: Number of Participants With AEs and SAEs
Time frame: Up to approximately 253 weeks
CE Phase: Number of Participants With AEs Leading to Discontinuation
Time frame: Up to approximately 253 weeks
CE Phase: Number of Participants With Adverse Events Leading to Dose Reduction or Delay
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
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
Time frame: Baseline (Day 1) and up to approximately 253 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: 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.
Related trials for Multiple Myeloma
Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 2
Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
Multiple Myeloma
Active, not recruitingPhase 3
A Phase III Study of Eque-cel in Subjects With Len-refractory RRMM (FUMANBA-03)
Multiple Myeloma
Active, not recruitingPhase 1/2
A Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Adult Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment
Multiple Myeloma
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
29 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Belantamab mafodotin and Nirogacestat in people with Multiple Myeloma, run by GlaxoSmithKline at 29 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 6 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United States, South Korea, Spain, Germany, Poland and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DE Phase: Number of Participants With Dose Limiting Toxicities (DLTs) (time frame: Up to 28 days). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2026.