The primary purpose is to determine the safety and tolerability of belantamab mafodotin in combination with other anti-cancer treatments (in each sub-study), and to establish the recommended Phase 2 dose for each combination treatment to explore in the cohort expansion phase. This study is the sub study of the Master protocol (NCT04126200).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
Belantamab Mafodotin will be administered.
GSK3174998 will be administered.
GSK Investigational Site
Fitzroy, Victoria, Australia
GSK Investigational Site
Toronto, Ontario, Canada
GSK Investigational Site
Stockholm, Sweden
DE Phase: Number of Participants With Dose Limiting Toxicities (DLT)
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, is 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 qualify as DLTs.
Time frame: Up to 21 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.
Time frame: Up to 170 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 the analysis of following hematology parameters: eosinophils, anemia, hemoglobin increased, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased, leukocytosis and white blood cell decreased. The laboratory parameters were graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5. Grade 1 (G1): mild; Grade 2 (G2): moderate; Grade 3 (G3: severe or medically significant. 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 and G3 are presented.
Time frame: Baseline (Day 1) and up to 170 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 the analysis of following chemistry parameters: Hypoglycemia, hypoalbuminemia, alkaline phosphatase (ALP) increased, alanine aminotransferase (ALT) increased, aspartate aminotransferase (AST) increased, blood bilirubin increased, creatine kinase (CPK) increased, creatinine increased, gamma glutamyl transferase (GGT) increased, hyperkalemia, blood lactate dehydrogenase (LDH) increased, hypermagnesemia, hypomagnesemia, hypernatremia, hypercalcemia, hypocalcemia and Serum OR Plasma Glomerular Filtration Rate (GFR) from creatinine adjusted for body surface area (BSA) SA (mL/sec/1.73m\^2)/chronic kidney disease. The laboratory parameters were graded according to CTCAE version 5. G1: mild; G2: moderate; G3: severe or medically significant. 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 and G3 are presented.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: Baseline (Day 1) and up to 170 weeks
Cohort Expansion (CE) Phase: Overall Response Rate (ORR)
Overall Response Rate (ORR) was defined as the percentage of participants with a confirmed PR or better as the best overall response (i.e., Partial Response \[PR\], 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). CR defined as negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND \<5% plasmacytomas in the bone marrow; sCR 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; VGPR 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; PR defined as ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to \<200 mg/24 h.
Time frame: Up to 170 weeks
DE Phase: Overall Response Rate (ORR)
ORR was defined as the percentage of participants with a confirmed partial response (PR) or better (i.e., PR, very good partial response \[VGPR\], complete response \[CR\] and stringent complete response \[sCR\]), according to the International Myeloma Working Group (IMWG) Response Criteria. CR = negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND \<5% plasmacytomas in the bone marrow; sCR=stringent complete response, CR as above PLUS normal serum free light-chain (FLC) assay ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; VGPR = serum and urine M-component detectable by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-component plus urine M-component \<100 mg/24 h; PR = ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to \<200 mg/24 h.
Time frame: Up to 170 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 \>= 25% but \< 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%.
Time frame: Up to 170 weeks
DE Phase: Percentage 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). CR = negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND \<5% plasmacytomas in the bone marrow; sCR=stringent complete response, CR as above PLUS normal serum free light-chain (FLC) assay ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; VGPR = serum and urine M-component detectable by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-component plus urine M-component \<100 mg/24 h; PR = ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to \<200 mg/24 h.
Time frame: Up to 170 weeks
CE Phase: Percentage 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). CR = negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND \<5% plasmacytomas in the bone marrow; sCR=stringent complete response, CR as above PLUS normal serum free light-chain (FLC) assay ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; VGPR = serum and urine M-component detectable by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-component plus urine M-component \<100 mg/24 h; PR = ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to \<200 mg/24 h.
Time frame: Up to 170 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).
Time frame: Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days)
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: Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days)
DE Phase: Plasma Concentration of Belantamab Mafodotin Total Antibody
Blood samples were collected for PK analysis of Belantamab mafodotin total antibody.
Time frame: Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days)
CE Phase: Plasma Concentration of Belantamab Mafodotin Plasma Total Antibody
Blood samples were collected for PK analysis of Belantamab mafodotin plasma total antibody.
Time frame: Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days)
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: Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days)
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: Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days)
DE Phase: OX40 Concentration When Administered in Combination With Belantamab Mafodotin
Blood samples were collected for PK analysis of OX40 when administered intravenously in combination with belantamab mafodotin.
Time frame: Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days)
CE Phase: OX40 Concentration When Administered in Combination With Belantamab Mafodotin
Blood samples were collected for PK analysis of OX40 when administered intravenously in combination with belantamab mafodotin.
Time frame: Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days)
DE Phase: Number of Participants With Post-baseline Positive Anti-drug Antibodies (ADAs) Against Belantamab Mafodotin
Serum samples collected for the analysis of the presence of ADAs using validated immunoassays. All samples were tested in screening assay, and positive samples were further characterized for antibody titers.
Time frame: Up to 170 weeks
CE Phase: Number of Participants With Post-baseline Positive ADAs Against Belantamab Mafodotin
Serum samples collected for the analysis of the presence of ADAs using validated immunoassays. All samples were tested in screening assay, and positive samples were further characterized for antibody titers.
Time frame: Up to 170 weeks
DE Phase: Number of Participants With Post-baseline Positive ADAs Against OX40
Serum samples collected for the analysis of the presence of ADAs using validated immunoassays. All samples were tested in screening assay, and positive samples were further characterized for antibody titers.
Time frame: Up to 170 weeks
CE Phase: Number of Participants With Post-baseline Positive ADAs Against OX40
Serum samples collected for the analysis of the presence of ADAs using validated immunoassays. All samples were tested in screening assay, and positive samples were further characterized for antibody titers.
Time frame: Up to 170 weeks
DE Phase: Concentration of ADAs Against Belantamab Mafodotin
Serum samples 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 170 weeks
CE Phase: Concentration of ADAs Against Belantamab Mafodotin
Serum samples 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 170 weeks
DE Phase: Concentration of ADAs Against OX40 When Administered in Combination With Belantamab Mafodotin
Serum samples 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 170 weeks
CE Phase: Concentration of ADAs Against OX40 When Administered in Combination With Belantamab Mafodotin
Serum samples 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 170 weeks
DE Phase: Number of Participants With Adverse Events of Special Interest (AESI)
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. Adverse Events of Special Interest (whether serious or non serious) were collected.
Time frame: Up to 170 weeks
CE Phase: Number of Participants With AESI
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.
Time frame: Up to 170 weeks
DE Phase: Number of Participants With Any Corneal Events 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. 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.
Time frame: Up to 170 weeks
CE Phase: Number of Participants With Any Corneal Events by Maximum Grade as Per CTCAE Grade
Corneal Events were examined.
Time frame: Up to 170 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 170 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 170 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 170 weeks
CE Phase: Overall Survival (OS)
OS is defined as the time from randomization until death due to any cause.
Time frame: Up to 170 weeks
CE Phase: Number of Participants With AEs and SAEs
AEs and SAEs were collected.
Time frame: Up to 170 weeks
CE Phase: Number of Participants With AEs Leading to Discontinuation
Number of participants with AEs leading to discontinuation were evaluated.
Time frame: Up to 170 weeks
CE Phase: Number of Participants With Dose Reduction or Delay
Number of participants with dose reduction or delay were evaluated.
Time frame: Up to 170 weeks
CE Phase: Number of Participants With Clinically Significant Changes in Hematology Lab Parameters
Blood samples were collected for the analysis of following hematology parameters: eosinophils, anemia, hemoglobin increased, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased, leukocytosis and white blood cell decreased. The laboratory parameters were graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5. Grade 1 (G1): mild; Grade 2 (G2): moderate; Grade 3 (G3: severe or medically significant. Higher grade indicates greater severity and an increase in CTCAE grade was defined relative to the Baseline grade.
Time frame: Up to 170 weeks
CE Phase: Number of Participants With Clinically Significant Changes in Clinical Chemistry Lab Parameters
Blood samples were collected for the analysis of following chemistry parameters: Hypoglycemia, hypoalbuminemia, alkaline phosphatase (ALP) increased, alanine aminotransferase (ALT) increased, aspartate aminotransferase (AST) increased, blood bilirubin increased, creatine kinase (CPK) increased, creatinine increased, gamma glutamyl transferase (GGT) increased, hyperkalemia, blood lactate dehydrogenase (LDH) increased, hypermagnesemia, hypomagnesemia, hypernatremia, hypercalcemia, hypocalcemia and chronic kidney disease. The laboratory parameters were graded according to CTCAE version 5. G1: mild; G2: moderate; G3: severe or medically significant. Higher grade indicates greater severity and an increase in CTCAE grade was defined relative to the Baseline grade.
Time frame: Up to 170 weeks