Platform Sub-study of Belantamab Mafodotin (GSK2857916) in Combination With aOX40 (GSK3174998) in Participants With RRMM
- Conditions
- Relapsed/Refractory Multiple Myeloma
- Interventions
- Registration Number
- NCT06160609
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 9
- 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.
- 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 autoimmune disease (current or history) or syndrome that required systemic treatment within the past 2 years.
- Exclusion for a recent (within the past 6 months) history of symptomatic pericarditis.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Belantamab mafodotin + GSK3174998 Belantamab Mafodotin - Belantamab mafodotin + GSK3174998 GSK3174998 -
- Primary Outcome Measures
Name Time Method DE Phase: Number of Participants With Dose Limiting Toxicities (DLT) Up to 21 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, 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.
DE Phase: Number of Participants With Adverse Events (AEs) Up to 170 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.
DE Phase: Number of Participants With Worst-Case Chemistry Results by Maximum Grade Increase Post - Baseline Relative to Baseline Baseline (Day 1) and up to 170 weeks 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.
Cohort Expansion (CE) Phase: Overall Response Rate (ORR) Up to 170 weeks 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.
DE Phase: Number of Participants With Worst-Case Hematology Results by Maximum Grade Increase Post - Baseline Relative to Baseline Baseline (Day 1) and up to 170 weeks 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.
- Secondary Outcome Measures
Name Time Method DE Phase: Number of Participants With Post-baseline Positive Anti-drug Antibodies (ADAs) Against Belantamab Mafodotin Up to 170 weeks 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.
DE Phase: Percentage of Participants Achieving Stringent Complete Response (SCR), Complete Response (CR), Very Good Partial Response (VGPR) and Partial Response (PR) Up to 170 weeks 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.
CE Phase: Number of Participants With Post-baseline Positive ADAs Against Belantamab Mafodotin Up to 170 weeks 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.
CE Phase: Percentage of Participants Achieving SCR, CR, VGPR and PR Up to 170 weeks 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.
DE Phase: Plasma Concentrations of Belantamab Mafodotin Antibody-Drug Conjugate (ADC) Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days) Blood samples were collected for PK analysis of belantamab mafodotin Antibody-Drug Conjugate (ADC).
CE Phase: Plasma Concentrations of Belantamab Mafodotin Antibody-Drug Conjugate (ADC) Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days) Blood samples were collected for PK analysis of Belantamab Mafodotin Antibody-Drug Conjugate (ADC).
CE Phase: Clinical Benefit Rate (CBR) Up to 170 weeks 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%.
DE Phase: Plasma Concentration of Belantamab Mafodotin Total Antibody Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days) Blood samples were collected for PK analysis of Belantamab mafodotin total antibody.
CE Phase: Plasma Concentration of Belantamab Mafodotin Plasma Total Antibody Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days) Blood samples were collected for PK analysis of Belantamab mafodotin plasma total antibody.
DE Phase: Plasma Concentrations of Belantamab Mafodotin Cys- Monomethyl Auristatin-F (Cys-mcMMAF) Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days) Blood samples were collected for PK analysis of belantamab mafodotin cys- monomethyl auristatin-F (cys-mcMMAF).
CE Phase: Plasma Concentrations of Belantamab Mafodotin Cys- Monomethyl Auristatin-F (Cys-mcMMAF) Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days) Blood samples were collected for PK analysis of Belantamab Mafodotin Cys- Monomethyl Auristatin-F (Cys-mcMMAF)
DE Phase: OX40 Concentration When Administered in Combination With Belantamab Mafodotin Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days) Blood samples were collected for PK analysis of OX40 when administered intravenously in combination with belantamab mafodotin.
CE Phase: OX40 Concentration When Administered in Combination With Belantamab Mafodotin Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days) Blood samples were collected for PK analysis of OX40 when administered intravenously in combination with belantamab mafodotin.
DE Phase: Number of Participants With Post-baseline Positive ADAs Against OX40 Up to 170 weeks 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.
CE Phase: Number of Participants With Post-baseline Positive ADAs Against OX40 Up to 170 weeks 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.
DE Phase: Concentration of ADAs Against Belantamab Mafodotin Up to 170 weeks 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.
CE Phase: Concentration of ADAs Against Belantamab Mafodotin Up to 170 weeks 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.
DE Phase: Concentration of ADAs Against OX40 When Administered in Combination With Belantamab Mafodotin Up to 170 weeks 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.
CE Phase: Concentration of ADAs Against OX40 When Administered in Combination With Belantamab Mafodotin Up to 170 weeks 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.
CE Phase: Time to Response (TTR) Up to 170 weeks 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).
CE Phase: Overall Survival (OS) Up to 170 weeks OS is defined as the time from randomization until death due to any cause.
CE Phase: Number of Participants With AEs and SAEs Up to 170 weeks AEs and SAEs were collected.
CE Phase: Number of Participants With AEs Leading to Discontinuation Up to 170 weeks Number of participants with AEs leading to discontinuation were evaluated.
CE Phase: Number of Participants With Dose Reduction or Delay Up to 170 weeks Number of participants with dose reduction or delay were evaluated.
CE Phase: Number of Participants With Clinically Significant Changes in Hematology Lab Parameters Up to 170 weeks 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.
DE Phase: Overall Response Rate (ORR) Up to 170 weeks 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.
CE Phase: Progression-free Survival (PFS) Up to 170 weeks 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.
CE Phase: Duration of Response (DoR) Up to 170 weeks 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.
DE Phase: Number of Participants With Adverse Events of Special Interest (AESI) Up to 170 weeks 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.
CE Phase: Number of Participants With AESI Up to 170 weeks 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.
DE Phase: Number of Participants With Any Corneal Events by Maximum Grade as Per CTCAE Grade Up to 170 weeks 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.
CE Phase: Number of Participants With Any Corneal Events by Maximum Grade as Per CTCAE Grade Up to 170 weeks Corneal Events were examined.
CE Phase: Number of Participants With Clinically Significant Changes in Clinical Chemistry Lab Parameters Up to 170 weeks 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.
Trial Locations
- Locations (1)
GSK Investigational Site
🇸🇪Stockholm, Sweden