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An Open-label, Dose Escalation Study in Japanese Participants With Relapsed/Refractory Multiple Myeloma Who Have Failed Prior Anti Myeloma Treatments

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03828292
Recruitment Status : Recruiting
First Posted : February 4, 2019
Last Update Posted : July 20, 2021
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
Belantamab mafodotin (GSK2857916) is a first in class, antibody dependent cellular cytotoxicity (ADCC) enhanced, humanized immunoglobulin G1 (IgG1) antibody-drug conjugate (ADC) which binds specifically to B cell maturation antigen (BCMA) expressed on tumor cells of all participants with multiple myeloma. This is a Phase 1, open label, dose escalation study to investigate safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and clinical activity of GSK2857916 when given as monotherapy (Part 1) or given as combination therapy (Part 2). Dose escalation will follow a 3+3 design.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Belantamab mafodotin Drug: Bortezomib Drug: Dexamethasone Drug: Pomalidomide Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 14 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Participants will receive GSK2857916 monotherapy during Part 1 (Dose escalation) of the study on a once every 21 days schedule. During Part 2, participants will receive GSK2857916 given in combination with Bortezomib/Dexamethasone on a once every 21 days schedule (Arm A) or with Pomalidomide/Dexamethasone on a once every 28 days schedule (Arm B).
Masking: None (Open Label)
Masking Description: This will be an open-label study.
Primary Purpose: Treatment
Official Title: A Phase I Open-Label, Dose Escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Clinical Activity of the Antibody Drug Conjugate GSK2857916 in Japanese Participants With Relapsed/Refractory Multiple Myeloma
Actual Study Start Date : March 14, 2019
Estimated Primary Completion Date : June 9, 2023
Estimated Study Completion Date : June 9, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Part 1: Belantamab mafodotin Monotherapy Drug: Belantamab mafodotin
Belantamab mafodotin will be administered as an intravenous infusion.

Experimental: Part 2: Arm A: Belantamab mafodotin+Bortezomib/Dexamethasone Drug: Belantamab mafodotin
Belantamab mafodotin will be administered as an intravenous infusion.

Drug: Bortezomib
Bortezomib solution for injection will be administered subcutaneously.

Drug: Dexamethasone
Dexamethasone tablets will be administered orally.

Experimental: Part 2: Arm B: Belantamab mafodotin+Pomalidomide/Dexamethasone Drug: Belantamab mafodotin
Belantamab mafodotin will be administered as an intravenous infusion.

Drug: Dexamethasone
Dexamethasone tablets will be administered orally.

Drug: Pomalidomide
Pomalidomide capsules will be administered orally.




Primary Outcome Measures :
  1. Part 1: Number of participants with dose limiting toxicities (DLTs) [ Time Frame: Day 1 to 21 of Cycle 1 (each cycle of 21 days) ]
    The number of participants with DLTs will be reported.

  2. Part 2: Arm A: Number of participants with DLTs [ Time Frame: Day 1 to 21 of Cycle 1 (each cycle of 21 days) ]
    The number of participants with DLTs will be reported.

  3. Part 2: Arm B: Number of participants with DLTs [ Time Frame: Day 1 to 28 of Cycle 1 (each cycle of 28 days) ]
    The number of participants with DLTs will be reported.

  4. Part 1 and Part 2: Number of participants with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to approximately 2.2 years ]
    AEs and SAEs will be collected.

  5. Part 1 and Part 2: Number of participants with abnormal hematology, clinical chemistry, urinalysis parameters [ Time Frame: Up to approximately 2.2 years ]
    Blood and urine samples will be collected for the assessment of hematology, clinical chemistry and urinalysis parameters.

  6. Part 1 and Part 2: Number of participants with abnormal vital signs [ Time Frame: Up to approximately 2.2 years ]
    Number of participants with abnormal vital signs will be assessed.

  7. Part 1 and Part 2: Number of participants with abnormal electrocardiogram (ECG) findings [ Time Frame: Up to approximately 2.2 years ]
    A 12-lead ECG will be obtained using an ECG machine. Number of participants with abnormal ECG parameters will be assessed.

  8. Part 1 and Part 2: Number of participants with abnormal physical examination findings [ Time Frame: Up to approximately 2.2 years ]
    Number of participants with abnormal findings in physical examination will be assessed.

  9. Part 1 and Part 2: Number of participants with abnormal ocular examination findings [ Time Frame: Up to approximately 2.2 years ]
    Number of participants with abnormal ocular examination findings will be reported.

  10. Part 1 and Part 2: Mean Eastern Cooperative Oncology Group (ECOG) scores [ Time Frame: Up to approximately 2.2 years ]
    The performance status of participants will be assessed using the ECOG Scale ranging from 0 (normal activity) to 5 (Dead).


Secondary Outcome Measures :
  1. Part 1: Area under the plasma concentration time curve from time 0 to the time of the last quantifiable concentration (AUC [0 to t]) for GSK2857916 following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15 (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.

  2. Part 2: Arm A: AUC (0 to t) for GSK2857916 following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.

  3. Part 2: Arm B: AUC (0 to t) for GSK2857916 following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (28-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.

  4. Part 1: Area under the plasma concentration-time curve from time 0 to the end of dosing (AUC [0 to tau]) for GSK2857916 following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15 (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.

  5. Part 2: Arm A: AUC (0 to tau) for GSK2857916 following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.

  6. Part 2: Arm B: AUC (0 to tau) for GSK2857916 following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (28-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.

  7. Part 1: Area under the plasma concentration-time curve from time 0 to infinite time (AUC [0 to inf]) for GSK2857916 following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15 (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.

  8. Part 2: Arm A: AUC (0 to inf) for GSK2857916 following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.

  9. Part 2: Arm B: AUC (0 to inf) for GSK2857916 following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (28-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.

  10. Part 1: Maximum observed plasma concentration (Cmax) for GSK2857916 following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15 (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.

  11. Part 2: Arm A: Cmax for GSK2857916 following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.

  12. Part 2: Arm B: Cmax for GSK2857916 following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (28-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.

  13. Part 1: Time to Cmax (Tmax) for GSK2857916 following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15 (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.

  14. Part 2: Arm A: Tmax for GSK2857916 following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.

  15. Part 2: Arm B: Tmax for GSK2857916 following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (28-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.

  16. Part 1: Systemic clearance (CL) for GSK2857916 following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15 (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.

  17. Part 2: Arm A: CL for GSK2857916 following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.

  18. Part 2: Arm B: CL for GSK2857916 following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (28-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.

  19. Part 1: Volume of distribution at steady state (Vss) for GSK2857916 following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15 (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.

  20. Part 2: Arm A: Vss for GSK2857916 following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.

  21. Part 2: Arm B: Vss for GSK2857916 following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (28-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.

  22. Part 1: Terminal phase half-life (T1/2) for GSK2857916 following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15 (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.

  23. Part 2: Arm A: T1/2 for GSK2857916 following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.

  24. Part 2: Arm B: T1/2 for GSK2857916 following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (28-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.

  25. Part 1: Concentration at the end of infusion of GSK2857916 following repeat dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15; Cycle 2 Day1, Cycle 3 Day1, Cycle 6 Day1, Cycle9 Day1, and Cycle12 Day1 (pre-dose, end of infusion); Cycle 16 Day1 (pre-dose) (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.

  26. Part 2: Arm A: Concentration at the end of infusion of GSK2857916 following repeat dose administration [ Time Frame: Up to approximately 2.2 years ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.

  27. Part 2: Arm B: Concentration at the end of infusion of GSK2857916 following repeat dose administration [ Time Frame: Up to approximately 2.2 years ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.

  28. Part 1: Trough plasma concentration (Ctrough) for GSK2857916 following repeat dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15; Cycle 2 Day1, Cycle 3 Day1, Cycle 6 Day1, Cycle9 Day1, and Cycle12 Day1 (pre-dose, end of infusion); Cycle 16 Day1 (pre-dose) (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.

  29. Part 2: Arm A: Ctrough for GSK2857916 following repeat dose administration [ Time Frame: Up to approximately 2.2 years ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.

  30. Part 2: Arm B: Ctrough for GSK2857916 following repeat dose administration [ Time Frame: Up to approximately 2.2 years ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.

  31. Part 1: Observed accumulation ratio for GSK2857916 following repeat dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15; Cycle 2 Day1, Cycle 3 Day1, Cycle 6 Day1, Cycle9 Day1, and Cycle12 Day1 (pre-dose, end of infusion); Cycle 16 Day1 (pre-dose) (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.

  32. Part 2: Arm A: Observed accumulation ratio for GSK2857916 following repeat dose administration [ Time Frame: Up to approximately 2.2 years ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.

  33. Part 2: Arm B: Observed accumulation ratio for GSK2857916 following repeat dose administration [ Time Frame: Up to approximately 2.2 years ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.

  34. Part 1: AUC (0 to t) for Cysteine maleimidocaproyl monomethyl auristatin F (cys-mcMMAF) following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15 (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.

  35. Part 2: Arm A: AUC (0 to t) for cys-mcMMAF following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.

  36. Part 2: Arm B: AUC (0 to t) for cys-mcMMAF following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (28-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.

  37. Part 1: AUC (0 to tau) for cys-mcMMAF following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15 (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.

  38. Part 2: Arm A: AUC (0 to tau) for cys-mcMMAF following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.

  39. Part 2: Arm B: AUC (0 to tau) for cys-mcMMAF following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (28-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.

  40. Part 1: AUC (0 to inf) for cys-mcMMAF following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15 (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.

  41. Part 2: Arm A: AUC (0 to inf) for cys-mcMMAF following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.

  42. Part 2: Arm B: AUC (0 to inf) for cys-mcMMAF following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (28-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.

  43. Part 1: Cmax for cys-mcMMAF following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15 (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.

  44. Part 2: Arm A: Cmax for cys-mcMMAF following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.

  45. Part 2: Arm B: Cmax for cys-mcMMAF following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (28-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.

  46. Part 1: Tmax for cys-mcMMAF following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15 (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.

  47. Part 2: Arm A: Tmax for cys-mcMMAF following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.

  48. Part 2: Arm B: Tmax for cys-mcMMAF following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (28-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.

  49. Part 1: T1/2 for cys-mcMMAF following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15 (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.

  50. Part 2: Arm A: T1/2 for cys-mcMMAF following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.

  51. Part 2: Arm B: T1/2 for cys-mcMMAF following single dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (28-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.

  52. Part 1: Concentration at end of infusion for cys-mcMMAF following repeat dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15; Cycle 2 Day1, Cycle 3 Day1, Cycle 6 Day1, Cycle9 Day1, and Cycle12 Day1 (pre-dose, end of infusion); Cycle 16 Day1 (pre-dose) (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.

  53. Part 2: Arm A: Concentration at end of infusion for cys-mcMMAF following repeat dose administration [ Time Frame: Up to approximately 2.2 years ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.

  54. Part 2: Arm B: Concentration at end of infusion for cys-mcMMAF following repeat dose administration [ Time Frame: Up to approximately 2.2 years ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.

  55. Part 1: Ctrough for cys-mcMMAF following repeat dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15; Cycle 2 Day1, Cycle 3 Day1, Cycle 6 Day1, Cycle9 Day1, and Cycle12 Day1 (pre-dose, end of infusion); Cycle 16 Day1 (pre-dose) (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.

  56. Part 2: Arm A: Ctrough for cys-mcMMAF following repeat dose administration [ Time Frame: Up to approximately 2.2 years ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.

  57. Part 2: Arm B: Ctrough for cys-mcMMAF following repeat dose administration [ Time Frame: Up to approximately 2.2 years ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.

  58. Part 1: Observed accumulation ratio for cys-mcMMAF following repeat dose administration [ Time Frame: Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15; Cycle 2 Day1, Cycle 3 Day1, Cycle 6 Day1, Cycle9 Day1, and Cycle12 Day1 (pre-dose, end of infusion); Cycle 16 Day1 (pre-dose) (21-day cycle) ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.

  59. Part 2: Arm A: Observed accumulation ratio for cys-mcMMAF following repeat dose administration [ Time Frame: Up to approximately 2.2 years ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.

  60. Part 2: Arm B: Observed accumulation ratio for cys-mcMMAF following repeat dose administration [ Time Frame: Up to approximately 2.2 years ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.

  61. Part 1 and Part 2: Number of participants who develop anti-drug antibodies (ADAs) against GSK2857916 [ Time Frame: Up to approximately 2.2 years ]
    Serum samples will be collected for analysis of presence of anti-GSK2857916 antibodies by a validated electrochemiluminescent immunoassay.

  62. Part 1 and Part 2: Titers of anti-GSK2857916 antibodies [ Time Frame: Up to approximately 2.2 years ]
    Serum samples will be collected for analysis of presence of anti-GSK2857916 antibodies by a validated electrochemiluminescent immunoassay.

  63. Part 1 and Part 2: Overall response rate [ Time Frame: Up to approximately 2.2 years ]
    Overall response rate is defined as the percentage of participants with a confirmed partial response or better, according to the International Myeloma Working Group (IMWG) response criteria, as assessed by the investigator.

  64. Part 1 and Part 2: Clinical benefit rate [ Time Frame: Up to approximately 2.2 years ]
    Clinical benefit rate is defined as the percentage of participants with a confirmed minimal response (MR) or better, according to the IMWG response criteria, as assessed by the investigator.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Provide signed written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
  • Male or female, 20 years or older (at the time consent is obtained).
  • ECOG performance status of 0 to 2.
  • Histologically or cytologically confirmed diagnosis of multiple myeloma as defined according to IMWG 2014, criteria in a participant who fulfills all of the following: has undergone stem cell transplant, or is considered transplant ineligible, Part 1: has received at least 2 prior lines of anti-myeloma drugs containing at least 1 proteasome inhibitor and at least 1 immunomodulator, Part 2: has received at least 1 prior line of anti-myeloma drugs; has demonstrated progression on, or within 60 days of completion of the last therapy.
  • Has measurable disease with at least one of the following: serum M-protein >=0.5 grams per deciliter (g/dL) (>=5 grams per liter [g/L]); Urine M-protein >=200 mg/24 hours; Serum free light chain (FLC) assay: Involved FLC level >=10 mg/dL (>=100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65).
  • Participants with a history of autologous stem cell transplant are eligible for study participation provided the following eligibility criteria are met: Transplant was >100 days prior to study enrolment; No active infection.
  • Female participants: Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. A female participant is eligible to participate if she is not pregnant or breast feeding, and at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP) or For Part 1 and Part 2 Arm A: Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1 percent per year), preferably with low user dependency, during the treatment period and for 4 months after the last dose of GSK2857916, and 7 months from the last dose of bortezomib (only Part 2 Arm A), and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study treatment. A WOCBP must have a negative highly sensitive serum pregnancy test (as required by local regulations) within 72 hours before the first dose of study treatment and agree to use effective contraception during the study and for 4 months after the last dose of GSK2857916, and 7 months from the last dose of bortezomib (only Part 2 Arm A); For Part 2 Arm B: Due to pomalidomide being a thalidomide analogue with risk for embryo-fetal toxicity and prescribed under a restricted distribution program, WOCBP participants will be eligible if they commit either to abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control, beginning 4 weeks prior to initiating treatment with pomalidomide, during therapy, during dose interruptions and continuing for 4 weeks following discontinuation of pomalidomide treatment. Thereafter, WOCBP participants must use a contraceptive method that is highly effective (with a failure rate of <1 percent per year) for a further 3 months, and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. Two negative pregnancy tests must be obtained prior to initiating pomalidomide therapy. The first test should be performed within 10 to 14 days and the second test within 24 hours prior to prescribing pomalidomide therapy. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
  • Male participants: Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Male participants are eligible to participate if they agree to the following from the time of first dose of study treatment until 6 months after the last dose of GSK2857916, 4 months after the last dose of bortezomib (only Part 2 Arm A), and 4 weeks after the last dose of pomalidomide (only Part 2 Arm B) to allow for clearance of any altered sperm: Refrain from donating sperm plus either: Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent; or must agree to use contraception/barrier as detailed: Agree to use a male condom even if they have undergone a successful vasectomy and female partner to use an additional highly effective contraceptive method with a failure rate of <1 percent per year as when having sexual intercourse with a woman of childbearing potential (including pregnant females).
  • All prior treatment-related toxicities (defined by National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 4.03, must be <=Grade 1 at the time of enrolment except for alopecia. Participants with Grade 2 peripheral neuropathy can be enrolled into Part 1 and Part 2 Arm B but not into Part 2 Arm A.
  • Adequate Organ System Function. Exclusion Criteria
  • Systemic anti-tumor-therapy within 14 days, or plasmapheresis within 7 days prior to the first dose of study treatment.
  • Symptomatic amyloidosis, active 'polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes' (POEMS) syndrome, active plasma cell leukemia at the time of screening.
  • Use of an investigational drug within 14 days or 5 half-lives, whichever is shorter, preceding the first dose of study treatment. Prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study treatment. Prior BCMA targeted therapy.
  • History of an allogeneic stem cell transplant.
  • Current use of prohibited medications/device or planned use of any of these during the study period.
  • Current corneal epithelial disease except mild punctate keratopathy
  • 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 multiple myeloma are eligible, provided they fulfil the required criteria.
  • Evidence of active mucosal or internal bleeding.
  • Any major surgery within the last 4 weeks.
  • Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions (including laboratory abnormalities) that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures.
  • Active infection requiring treatment (antibiotic, antiviral, or antifungal treatment).
  • Evidence of severe or uncontrolled systemic diseases.
  • Malignancies other than disease under study are excluded, except for any other malignancy from which the participant has been disease-free for more than 2 years and, in the opinion of the investigators and Medical Monitor, will not affect the evaluation of the effects of this clinical study treatment on the currently targeted malignancy (multiple myeloma).
  • Evidence of cardiovascular risk including any of the following:

    1. Corrected QT interval Fridericia (QTcF) interval >=470 milliseconds (msecs) (the QT interval values must be corrected for heart rate by Fridericia's formula [QTcF])
    2. Evidence of current clinically significant uncontrolled arrhythmias, including clinically significant ECG abnormalities such as 2nd degree (Type II) or 3rd degree atrioventricular (AV) block.
    3. History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 6 months of Screening.
    4. Class III or IV heart failure as defined by the New York Heart Association functional classification system
    5. Uncontrolled hypertension
  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to GSK2857916 or any of the components of the study treatment.
  • Pregnant or lactating female or female who are interrupting lactation.
  • Known human Immunodeficiency virus (HIV) infection.
  • Presence of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb) or hepatitis B core antibody (HBcAb at Screening or within 3 months prior to first dose of study treatment).
  • Positive hepatitis C antibody test result or positive hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment. Participants with positive hepatitis C antibody due to prior resolved disease can only be enrolled, if a confirmatory negative hepatitis C RNA test is obtained. Hepatitis RNA testing is optional and participants with negative hepatitis C antibody test are not required to also undergo hepatitis C RNA testing.
  • Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. Stable chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if participant otherwise meets entry criteria.
  • Previously diagnosed with interstitial lung disease or current complication of interstitial lung disease.

Additional Exclusion Criteria for Part 2 Arm A

  • Intolerant to bortezomib or refractory to bortezomib.
  • Ongoing Grade 2 or higher peripheral neuropathy or neuropathic pain.
  • Intolerance or contraindications to herpes zoster prophylaxis Additional Exclusion Criteria for Part 2 Arm B
  • Prior pomalidomide use.
  • Intolerance or contraindications to antithrombotic prophylaxis.
  • Active or history of venous thromboembolism within 3 months prior to first dose of study treatment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03828292


Contacts
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Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com

Locations
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Japan
GSK Investigational Site Recruiting
Aichi, Japan, 467-8602
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Shinsuke Iida         
GSK Investigational Site Recruiting
Okayama, Japan, 701-1192
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Kazutaka Sunami         
GSK Investigational Site Recruiting
Tokyo, Japan, 135-8550
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Yuko Mishima         
GSK Investigational Site Recruiting
Tokyo, Japan, 150-8935
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Kenshi Suzuki         
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03828292    
Other Study ID Numbers: 207504
First Posted: February 4, 2019    Key Record Dates
Last Update Posted: July 20, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
Antibody drug conjugate
Dose-escalation
GSK2857916
Japanese
Relapsed/Refractory Multiple Myeloma
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Bortezomib
Pomalidomide
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunologic Factors
Angiogenesis Inhibitors