Belantamab mafodotin is an antibody-drug conjugate (ADC) containing humanized anti- B-cell maturation antigen (BCMA) monoclonal antibody (mAb). Renal impairment is a major complication of multiple myeloma (MM) and the majority of MM participants is either at risk or already has renal dysfunction at initial diagnosis. The purpose of this study is to assess the pharmacokinetics (PK), safety, and tolerability of belantamab mafodotin monotherapy in participants with RRMM, who have had at least 3 lines of prior treatment (or at least 2 lines of prior treatment if ineligible for autologous stem cell transplantation ) and have either normal or impaired renal functions. The study will consist of two parts: part 1 will include participants with normal/mildly impaired renal function and severe renal impairment and part 2 will include participants with end-stage renal disease (ESRD), where participants are either not undergoing or require hemodialysis. Participants will be administered belantamab mafodotin at a dose of 2.5 milligram per kilogram (mg/kg) intravenously once in three weeks (Q3W) dosing in Part 1. Based on the Part 1 Safety/Pharmacokinetic (PK) data, Part 2 participants will be administered the dose of either 2.5 mg/kg or 1.9 mg/kg (or other adjusted dose). Participants will be treated with belantamab mafodotin monotherapy until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, or end of study, whichever occurs first. This study will include a screening phase, treatment phase, follow-up phase and a post analysis continued treatment (PACT) phase . The total duration of the study is approximately up to 48 months.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
36
Belantamab mafodotin will be provided as lyophilized powder which will be available as 100 milligrams per vial (mg/vial) in single-use vial for reconstitution. Lyophilized belantamab mafodotin will reconstituted using water for injection, dilute with normal 0.9 % saline before use.
GSK Investigational Site
Tucson, Arizona, United States
GSK Investigational Site
Beverly Hills, California, United States
GSK Investigational Site
Sacramento, California, United States
GSK Investigational Site
Jacksonville, Florida, United States
GSK Investigational Site
Plantation, Florida, United States
GSK Investigational Site
Chicago, Illinois, United States
GSK Investigational Site
Westwood, Kansas, United States
GSK Investigational Site
Baltimore, Maryland, United States
GSK Investigational Site
Chapel Hill, North Carolina, United States
GSK Investigational Site
Portland, Oregon, United States
...and 9 more locations
Part 1: Maximum observed plasma concentration (Cmax) of GSK2857916
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Up to Day 85
Part 1: Time to Cmax (Tmax) of GSK2857916
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Up to Day 85
Part 1: Concentration of GSK2857916 at the end of infusion (C-EOI)
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Cycle 1 up to Cycle 3: end infusion (EOI) (each cycle is 21 days)
Part 1: Predose plasma concentration (Ctrough) of GSK2857916
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Predose on Cycle 1 and up to Cycle 3 (each cycle is 21 days)
Part 1: AUC over the dosing interval (AUC[0-tau]) of GSK2857916
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Up to Day 85
Part 1: Last time point where the concentration is above the limit of quantification (Tlast) of GSK2857916
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Up to Day 85
Part 1: Cmax of total monoclonal antibody (mAb)
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Up to Day 85
Part 1: Tmax of total mAb
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Up to Day 85
Part 1: Ctrough of total mAb
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Predose on Cycle 1 and up to Cycle 3 (each cycle is 21 days)
Part 1: C-EOI of total mAb
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Cycle 1 up to Cycle 3: end infusion (EOI) (each cycle is 21 days)
Part 1: AUC(0-tau) of total mAb
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Up to Day 85
Part 1: Tlast of total mAb
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Up to Day 85
Part 1: Cmax of Cys Monomethyl Auristatin F (cys-mcMMAF)
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Up to Day 85
Part 1: Tmax of cys-mcMMAF
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Up to Day 85
Part 1: C-EOI of cys-mcMMAF
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Cycle 1 up to Cycle 3: end infusion (EOI) (each cycle is 21 days)
Part 1: AUC(0-168 hours) of cys-mcMMAF
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Predose and up to 168 hours
Part 1: Tlast of cys-mcMMAF
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Up to Day 85
Part 2: Cmax of GSK2857916
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Up to Day 85
Part 2: Tmax of GSK2857916
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Up to Day 85
Part 2: C-EOI of GSK2857916
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Cycle 1 up to Cycle 3: end infusion (EOI) (each cycle is 21 days)
Part 2: Ctrough of GSK2857916
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Predose on Cycle 1 and up to Cycle 3 (each cycle is 21 days)
Part 2: AUC(0-tau) of GSK2857916
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Up to Day 85
Part 2: Tlast of GSK2857916
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Up to Day 85
Part 2: Cmax of total mAb
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Up to Day 85
Part 2: Tmax of total mAb
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Up to Day 85
Part 2: C-EOI of mAb
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Cycle 1 up to Cycle 3: end infusion (EOI) (each cycle is 21 days)
Part 2: Ctrough of total mAb
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Predose on Cycle 1 up to Cycle 3 (each cycle is 21 days)
Part 2: AUC(0-tau) of total mAb
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Up to Day 85
Part 2: Tlast of total mAb
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Up to Day 85
Part 2: Cmax of cys-mcMMAF
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Up to Day 85
Part 2: Tmax of cys-mcMMAF
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Up to Day 85
Part 2: C-EOI of cys-mcMMAF
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Cycle 1 up to Cycle 3: end infusion (EOI) (each cycle is 21 days)
Part 2: AUC(0-168 hours) of cys-mcMMAF
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Predose and up to 168 hours
Part 2: Tlast of cys-mcMMAF
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Up to Day 85
Part 1 and Part 2: Change from Baseline in Vital Signs- Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) (millimeter of mercury [mmHg])
Vital signs will be measured after resting for at least 5 minutes.
Time frame: Baseline and up to 48 months
Part 1 and Part 2: Change from Baseline in Vital Sign- Heart rate (beats per minute)
Vital signs will be measured after resting for at least 5 minutes.
Time frame: Baseline and up to 48 months
Part 1 and Part 2: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
AEs and SAEs will be collected at specified time points.
Time frame: Up to 48 months
Part 1 and Part 2: Number of participants with toxicity grading for clinical laboratory parameters
Time frame: Up to 48 months
Part 1 and Part 2: Change from baseline in physical examination parameter
Physical examination parameter will include assessment of weight only.
Time frame: Baseline and up to 48 months
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