Platform Sub-study of Belantamab Mafodotin (GSK2857916) in Combination With aOX40 (GSK3174998) in Participants With RRMM

Relapsed/Refractory Multiple Myeloma Clinical Trial

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 1 - Belantamab Mafodotin and aOX40 (GSK3174998) in Combination

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT06160609
• Other study ID #: 208887 Sub Study 1
• Secondary ID: 2019-001138-32
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: October 7, 2019
• Est. completion date: January 9, 2023

Study information

• Verified date: February 2024
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: January 9, 2023
• Est. primary completion date: January 9, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Relapsed/Refractory Multiple Myeloma

Intervention

Drug:
• Belantamab Mafodotin
Belantamab Mafodotin will be administered.
• GSK3174998
GSK3174998 will be administered.

Locations

Country	Name	City	State
Australia	GSK Investigational Site	Fitzroy	Victoria
Canada	GSK Investigational Site	Toronto	Ontario
Sweden	GSK Investigational Site	Stockholm

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

Australia,  Canada,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 21 days
Primary	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.	Up to 170 weeks
Primary	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.	Baseline (Day 1) and up to 170 weeks
Primary	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.	Baseline (Day 1) and up to 170 weeks
Primary	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.	Up to 170 weeks
Secondary	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.	Up to 170 weeks
Secondary	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%.	Up to 170 weeks
Secondary	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.	Up to 170 weeks
Secondary	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.	Up to 170 weeks
Secondary	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).	Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days)
Secondary	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).	Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days)
Secondary	DE Phase: Plasma Concentration of Belantamab Mafodotin Total Antibody	Blood samples were collected for PK analysis of Belantamab mafodotin total antibody.	Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days)
Secondary	CE Phase: Plasma Concentration of Belantamab Mafodotin Plasma Total Antibody	Blood samples were collected for PK analysis of Belantamab mafodotin plasma total antibody.	Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days)
Secondary	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).	Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days)
Secondary	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)	Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days)
Secondary	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.	Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days)
Secondary	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.	Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days)
Secondary	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.	Up to 170 weeks
Secondary	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.	Up to 170 weeks
Secondary	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.	Up to 170 weeks
Secondary	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.	Up to 170 weeks
Secondary	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.	Up to 170 weeks
Secondary	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.	Up to 170 weeks
Secondary	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.	Up to 170 weeks
Secondary	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.	Up to 170 weeks
Secondary	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.	Up to 170 weeks
Secondary	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.	Up to 170 weeks
Secondary	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.	Up to 170 weeks
Secondary	CE Phase: Number of Participants With Any Corneal Events by Maximum Grade as Per CTCAE Grade	Corneal Events were examined.	Up to 170 weeks
Secondary	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.	Up to 170 weeks
Secondary	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.	Up to 170 weeks
Secondary	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).	Up to 170 weeks
Secondary	CE Phase: Overall Survival (OS)	OS is defined as the time from randomization until death due to any cause.	Up to 170 weeks
Secondary	CE Phase: Number of Participants With AEs and SAEs	AEs and SAEs were collected.	Up to 170 weeks
Secondary	CE Phase: Number of Participants With AEs Leading to Discontinuation	Number of participants with AEs leading to discontinuation were evaluated.	Up to 170 weeks
Secondary	CE Phase: Number of Participants With Dose Reduction or Delay	Number of participants with dose reduction or delay were evaluated.	Up to 170 weeks
Secondary	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.	Up to 170 weeks
Secondary	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.	Up to 170 weeks