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Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Clinical Activity of GSK2857916

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02064387
Recruitment Status : Completed
First Posted : February 17, 2014
Results First Posted : September 26, 2019
Last Update Posted : September 26, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
This study will assess the safety, pharmacokinetic (PK), pharmacodynamic (PD) and the therapeutic potential of GSK2857916 in subjects with multiple myeloma (MM) and lymphomas that express B cell maturation antigen (BCMA). The hypothesis is that GSK2857916 can be safely administered to subjects with MM and with BCMA positive malignancies at doses where target engagement can be demonstrated. This study will determine if adequate target engagement of BCMA receptors translates into clinical benefit for subjects with MM and BCMA positive lymphomas. The study will consists of two parts: a Part 1 dose escalation phase and a Part 2 expansion phase for safety, tolerability, PK, PD, and clinical activity testing. The study will enroll a total of approximately 80-95 subjects with relapsed/refractory MM or BCMA-expressing hematologic malignancies. The maximum dose to be administered in this trial will not exceed 5 milligram/kilogram(mg/kg).

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: GSK2857916 Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 79 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Open-label, Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Clinical Activity of the Antibody Drug Conjugate GSK2857916 in Subjects With Relapsed/Refractory Multiple Myeloma and Other Advanced Hematologic Malignancies Expressing BCMA
Actual Study Start Date : July 29, 2014
Actual Primary Completion Date : August 31, 2018
Actual Study Completion Date : August 1, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Schedule 1 Part 1
Participants will receive GSK2857916 intravenously over 60 minutes (one dose) every 3 weeks (21 day cycle) for a maximum of 16 cycles.
Drug: GSK2857916
A clear or opalescent solution for IV infusion with unit dose strength of 20 mg/mililiter (mL) for multiple dose levels.

Experimental: Schedule 2 Part 1
Participants may receive GSK2857916 intravenously over 60 minutes (one dose) once weekly for three consecutive weeks followed by 1 week of rest (28 day cycle) for a maximum of 16 cycles.
Drug: GSK2857916
A clear or opalescent solution for IV infusion with unit dose strength of 20 mg/mililiter (mL) for multiple dose levels.

Experimental: Schedule 1 Part 2
Participants will receive the dose and schedule of GSK2857916 evaluated in Part 1 that is selected for further evaluation in Part 2 for up to 16 cycles.
Drug: GSK2857916
A clear or opalescent solution for IV infusion with unit dose strength of 20 mg/mililiter (mL) for multiple dose levels.

Experimental: Schedule 2 Part 2
Participants may receive the dose and schedule of GSK2857916 evaluated in Part 1 that is selected for further evaluation in Part 2 for a maximum of 16 cycles.
Drug: GSK2857916
A clear or opalescent solution for IV infusion with unit dose strength of 20 mg/mililiter (mL) for multiple dose levels.




Primary Outcome Measures :
  1. Number of Participants With Serious Adverse Events (SAEs) and Common (>=5%) Non-serious Adverse Events- Part 1 [ Time Frame: Up to 21.6 months (maximum duration of follow-up from first dose to last contact or death) ]
    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, at any dose, results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, other medical events according to medical or scientific judgement and all events of possible study treatment-induced liver injury with hyperbilirubinemia. Part 1 Population comprised of all Part 1 participants (exclusively MM) who received at least one dose of GSK2857916. SAEs and common (>=5%) non-SAEs is presented.

  2. Number of Participants With SAEs and Common (>=5%) Non-serious Adverse Events- Part 2 [ Time Frame: Up to 24.2 months (maximum duration of follow-up from first dose to last contact or death) ]
    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, at any dose, results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, other medical events according to medical or scientific judgement and all events of possible study treatment-induced liver injury with hyperbilirubinemia. Part 2 MM Population comprised of all Part 2 MM participants who received at least one dose of GSK2857916. SAEs and common (>=5%) non-SAEs is presented.

  3. Number of Participants With Dose-limiting Toxicities (DLTs) During the Determinative Period- Part 1 [ Time Frame: Up to Day 21 (from first dose) ]
    An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of the following criteria:albuminuria>=2000mgper24 hour which has been confirmed by repeat test at least7 days apart and is not considered to be related to disease progression, Grade4 neutropenia (without fever) lasting>=7 days, febrile neutropenia lasting>=72 hours, Grade>=3 thrombocytopenia associated with bleeding where estimated blood loss is>10 milliliter orGrade4 thrombocytopenia lasting>7 days and not responding to platelet transfusions, anyGrade3 or greaternon-hematologic toxicity as described in Common National Cancer Institute-Terminology Criteria for Adverse Events version4.0 with the exception of the following Grade3 events that can be controlled within48 hours with routine supportive measures and clinically asymptomatic electrolyte abnormalities which can be corrected within48 hours and liver toxicity meeting pre-specified GSK liver stopping criteria.

  4. Number of Participants With Grade Change From Baseline in Vital Signs-Part 1 [ Time Frame: Baseline and Up to 21.6 months (maximum duration of follow-up from first dose to last contact or death) ]
    Vital signs included systolic blood pressure (SBP), diastolic blood pressure (DBP), temperature (Temp) and heart rate (HR). SBP and DBP were graded using National Cancer Institute-Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0. For SBP: Grade 0-<120 millimeters of mercury[mmHg], 120-139 mmHg[Grade 1], 140-159 mmHg[Grade 2], >=160 mmHg[Grade 3]); For DBP: <80 mmHg [Grade 0], 80-89[Grade 1], 90-99[Grade 2], >=100 mmHg[Grade 3]). An increase is defined as an increase in CTCAE grade relative to Baseline grade. Baseline was defined as the latest pre-dose assessment with a non-missing value, including unscheduled visits. Data for worst-case post Baseline is presented.

  5. Number of Participants With Grade Change From Baseline in Vital Signs-Part 2 [ Time Frame: Baseline and Up to 24.2 months (maximum duration of follow-up from first dose to last contact or death) ]
    Vital signs included SBP, DBP, Temp and HR. SBP and DBP were graded using NCI CTCAE version 4.0. For SBP: Grade 0-<120 mmHg, 120-139 mmHg[Grade 1], 140-159 mmHg[Grade 2], >=160 mmHg[Grade 3]); For DBP: <80 mmHg [Grade 0], 80-89[Grade 1], 90-99[Grade 2], >=100 mmHg[Grade 3]). An increase is defined as an increase in CTCAE grade relative to Baseline grade. Baseline was defined as the latest pre-dose assessment with a non-missing value, including unscheduled visits. Data for worst-case post Baseline is presented.

  6. Number of Participants With Change From Baseline in Heart Rate and Temperature-Part 1 [ Time Frame: Baseline and Up to 21.6 months (maximum duration of follow-up from first dose to last contact or death) ]
    The following criteria was used to flag vital signs of potential clinical importance: change from Baseline in heart rate (decrease to <60 beats per minute [bpm] and increase to >100 bpm) and change in temperature from Baseline(increase to >=38 or decrease to <=35 degree centigrade). Baseline was defined as the latest pre-dose assessment with a non-missing value, including unscheduled visits. Data for worst-case post Baseline is presented.

  7. Number of Participants With Change From Baseline in Heart Rate and Temperature-Part 2 [ Time Frame: Baseline and Up to 24.2 months (maximum duration of follow-up from first dose to last contact or death) ]
    The following criteria was used to flag vital signs of potential clinical importance: change from Baseline in heart rate (decrease to <60 bpm and increase to >100 bpm) and change in temperature from Baseline(increase to >=38 or decrease to <=35 degree centigrade). Baseline was defined as the latest pre-dose assessment with a non-missing value, including unscheduled visits. Data for worst-case post Baseline is presented.

  8. Number of Participants With Grade Change From Baseline in Clinical Chemistry Data-Part 1 [ Time Frame: Baseline and Up to 21.6 months (maximum duration of follow-up from first dose to last contact or death) ]
    Blood samples were collected for the analysis of following clinical chemistry parameters: albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (T.Bil.), calcium (Ca), creatinine (Creat), creatinine kinase (CK), gamma glutamyl transferase (GGT), glucose (Gl), potassium (Pot), magnesium (Mg), sodium (Sod), phosphate (Ph) and urate. Values(Hyper and hypo)for Gl, Pot, Mg, Sod and Ca is presented. Laboratory parameters were graded according to NCI-CTCAE version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences; Grade 5: death related to AE. All increases are an increase in grade from Baseline. Baseline was the latest pre-dose assessment with a non-missing value, including unscheduled visits. Data for worst-case post Baseline is presented.

  9. Number of Participants With Grade Change From Baseline in Clinical Chemistry Data-Part 2 [ Time Frame: Baseline and Up to 24.2 months (maximum duration of follow-up from first dose to last contact or death) ]
    Blood samples were collected for the analysis of following clinical chemistry parameters: albumin,ALP,ALT,AST,T.Bil.,Ca, Creat,CK, GGT,Gl, Pot,Mg, Sod, Ph and urate. Values(Hyper and hypo)for Gl, Pot, Mg, Sod and Ca is presented. Laboratory parameters were graded according to NCI-CTCAE version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences; Grade 5: death related to AE. All increases are an increase in grade from Baseline. Baseline was the latest pre-dose assessment with a non-missing value, including unscheduled visits. Data for worst-case post Baseline is presented.

  10. Number of Participants With Change From Baseline in Clinical Chemistry Data With Respect to Normal Range-Part 1 [ Time Frame: Baseline and Up to 21.6 months (maximum duration of follow-up from first dose to last contact or death) ]
    Blood samples were collected for the analysis of following clinical chemistry parameters: direct bilirubin (D.Bil.), chloride, carbon dioxide (CO2), lactate dehydrogenase (LDH), total protein (T.Pro) and urea or blood urea nitrogen (BUN). Baseline was defined as latest pre-dose assessment with a non-missing value, including unscheduled visits. A laboratory value that is outside the reference range was considered either high abnormal (value above the upper limit of the reference range) or low abnormal (value below the lower limit of the reference range). If values were unchanged (example: High to High), or whose value became normal, were recorded in the 'To Normal or No Change (NC)' category. Participants were counted twice if the participant "Decreased to low" and "Increased to high" during post-Baseline. Data for worst-case post Baseline is presented.

  11. Number of Participants With Change From Baseline in Clinical Chemistry Data With Respect to Normal Range-Part 2 [ Time Frame: Baseline and Up to 24.2 months (maximum duration of follow-up from first dose to last contact or death) ]
    Blood samples were collected for the analysis of following clinical chemistry parameters: D.Bil., chloride, CO2, LDH, T.Pro and BUN. Baseline was defined as latest pre-dose assessment with a non-missing value, including unscheduled visits.A laboratory value that is outside the reference range was considered either high abnormal (value above the upper limit of the reference range) or low abnormal (value below the lower limit of the reference range). If values were unchanged (example: High to High), or whose value became normal, were recorded in the 'To Normal or NC' category. Participants were counted twice if the participant 'Decreased to Low' and 'Increased to High' during post-Baseline.Data for worst-case post Baseline is presented.

  12. Number of Participants With Grade Change From Baseline in Hematology Data-Part 1 [ Time Frame: Baseline and Up to 21.6 months (maximum duration of follow-up from first dose to last contact or death) ]
    Blood samples were collected for the analysis of following hematology parameters: hemoglobin (Hb), lymphocytes (Lymph), neutrophils (Neutro), platelet count (PC), and leukocytes (leuko). The laboratory parameters were graded according to NCI-CTCAE version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences; Grade 5: death related to AE. Baseline was defined as latest pre-dose assessment with a non-missing value, including unscheduled visits. An increase is defined as an increase in CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented.

  13. Number of Participants With Grade Change From Baseline in Hematology Data-Part 2 [ Time Frame: Baseline and Up to 24.2 months (maximum duration of follow-up from first dose to last contact or death) ]
    Blood samples were collected for the analysis of following hematology parameters: Hb, Lymph, Neutro, PC, and leuko. The laboratory parameters were graded according to NCI-CTCAE version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences; Grade 5: death related to AE. Baseline was defined as the latest pre-dose assessment with a non-missing value, including unscheduled visits.An increase is defined as an increase in CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented.

  14. Number of Participants With Change From Baseline in Hematology Data With Respect to Normal Range-Part 1 [ Time Frame: Baseline and Up to 21.6 months (maximum duration of follow-up from first dose to last contact or death) ]
    Blood samples were collected for the analysis of following hematology parameters: basophils (baso), eosinophils (Eosino), hematocrit (Hct), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), monocytes (Mono), erythrocytes (Erythro) and reticulocytes (Reticu). A laboratory value that was outside the reference range was considered either high abnormal (value above the upper limit of the reference range) or low abnormal (value below the lower limit of the reference range). Baseline was defined as latest pre-dose assessment with a non-missing value, including unscheduled visits. If values were unchanged (example: High to High), or whose value became normal, were recorded in the 'To Normal or NC' category. Participants were counted twice if the participant 'Decreased to Low' and 'Increased to High' during post-Baseline.Data at worst-case post Baseline is presented.

  15. Number of Participants With Change From Baseline in Hematology Data With Respect to Normal Range-Part 2 [ Time Frame: Baseline and Up to 24.2 months (maximum duration of follow-up from first dose to last contact or death) ]
    Blood samples were collected for the analysis of following hematology parameters: baso, Eosino, Hct, MCHC, MCH, MCV, Mono, Erythro and Reticu. A laboratory value that was outside the reference range was considered either high abnormal (value above the upper limit of the reference range) or low abnormal (value below the lower limit of the reference range). Baseline was defined as latest pre-dose assessment with a non-missing value, including unscheduled visits. If values were unchanged (example: High to High), or whose value became normal, were recorded in the 'To Normal or NC' category. Participants were counted twice if the participant 'Decreased to Low' and 'Increased to High' during post-Baseline.Data at worst-case post Baseline is presented.

  16. Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method -Part 1 [ Time Frame: Baseline and Up to 21.6 months (maximum duration of follow-up from first dose to last contact or death) ]
    Urine samples were collected to assess urine occult blood (OB) and urine protein (Pro). The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters were recorded as no change/decreased, increase to small (indicated by trace and 1+), increase to moderate (indicated by 2+) and increase to large (indicated by 3+ and above) for urine OB and no change/decreased, increase to trace, increase to 1+, increase to 2+ and increase to 3+ for urine Pro indicating proportional concentrations in the urine sample. Baseline was the latest pre-dose assessment with a non-missing value, including unscheduled visits. Data for worst-case post Baseline is presented.

  17. Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method -Part 2 [ Time Frame: Baseline and Up to 24.2 months (maximum duration of follow-up from first dose to last contact or death) ]
    Urine samples were collected to assess urine OB and urine Pro. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters were recorded as no change/decreased, increase to small (indicated by trace and 1+), increase to moderate (indicated by 2+) and increase to large (indicated by 3+ and above) for urine OB and no change/decreased, increase to trace, increase to 1+, increase to 2+ and increase to 3+ for urine Pro indicating proportional concentrations in the urine sample. Baseline was the latest pre-dose assessment with a non-missing value, including unscheduled visits. Data for worst-case post Baseline is presented.

  18. Change From Baseline in Urine Protein Excretion (24 Hour)-Part 1: GSK2857916 0.06 mg/kg [ Time Frame: Baseline and Day 1 (Cycle 2 and 3) ]
    Urine samples were collected to assess urine Pro. Baseline was the latest pre-dose assessment with a non-missing value, including unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data for change from Baseline in urine Pro. excretion (24 hour) is presented

  19. Change From Baseline in Urine Protein Excretion (24 Hour)-Part 1: GSK2857916 0.03 mg/kg and 0.12 mg/kg [ Time Frame: Baseline and Day 1 (Cycle 2) ]
    Urine samples were collected to assess urine Pro. Baseline was the latest pre-dose assessment with a non-missing value, including unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data for change from Baseline in urine Pro. excretion (24 hour) is presented

  20. Change From Baseline in Urine Protein Excretion (24 Hour)-Part 1: GSK2857916 0.24 mg/kg [ Time Frame: Baseline and Day 1 (Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 13,14, 15) ]
    Urine samples were collected to assess urine Pro. Baseline was the latest pre-dose assessment with a non-missing value, including unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data for change from Baseline in urine Pro. excretion (24 hour) is presented

  21. Change From Baseline in Urine Protein Excretion (24 Hour)-Part 1: GSK2857916 0.48 mg/kg [ Time Frame: Baseline and Day 1 (Cycle 2, 3, 5, 6, 7, 8) ]
    Urine samples were collected to assess urine Pro. Baseline was the latest pre-dose assessment with a non-missing value, including unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data for change from Baseline in urine Pro. excretion (24 hour) is presented

  22. Change From Baseline in Urine Protein Excretion (24 Hour)-Part 1: GSK2857916 0.96 mg/kg [ Time Frame: Baseline and Day 1 (Cycle 2, 3, 4, 5, 6) ]
    Urine samples were collected to assess urine Pro. Baseline was the latest pre-dose assessment with a non-missing value, including unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data for change from Baseline in urine Pro. excretion (24 hour) is presented

  23. Change From Baseline in Urine Protein Excretion (24 Hour)-Part 1: GSK2857916 1.92 mg/kg [ Time Frame: Baseline and Day 1 (Cycle 2, 3, 4, 5, 6, 7, 8, 11, 12, 13, 14, 16) ]
    Urine samples were collected to assess urine Pro. Baseline was the latest pre-dose assessment with a non-missing value, including unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data for change from Baseline in urine Pro. excretion (24 hour) is presented

  24. Change From Baseline in Urine Protein Excretion (24 Hour)-Part 1: GSK2857916 2.50 mg/kg [ Time Frame: Baseline and Day 1 (Cycle 2, 3, 4, 5, 6, 7, 8, 10, 12, 13, 14, 15, 16) ]
    Urine samples were collected to assess urine Pro. Baseline was the latest pre-dose assessment with a non-missing value, including unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data for change from Baseline in urine Pro. excretion (24 hour) is presented

  25. Change From Baseline in Urine Protein Excretion (24 Hour)-Part 1: GSK2857916 3.40 mg/kg and 4.60 mg/kg [ Time Frame: Baseline and Day 1 (Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16) ]
    Urine samples were collected to assess urine Pro. Baseline was the latest pre-dose assessment with a non-missing value, including unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data for change from Baseline in urine Pro. excretion (24 hour) is presented

  26. Change From Baseline in Urine Protein Excretion (24 Hour)-Part 2 [ Time Frame: Baseline and Day 1 (Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16) ]
    Urine samples were collected to assess urine Pro. Baseline was the latest pre-dose assessment with a non-missing value, including unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data for change from Baseline in urine Pro. excretion (24 hour) is presented


Secondary Outcome Measures :
  1. Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC[0-infinity]) of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM- Part 1 [ Time Frame: Pre-dose, 30 minutes post start of infusion (SOI), at end of infusion (EOI), 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1) ]
    Blood samples were collected at designated timepoints. Pharmacokinetic (PK) parameters of GSK2857916 were calculated using non-compartmental methods. NA indicates that geometric coefficient of variation could not be calculated for a single participant.

  2. AUC[0-infinity] of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM- Part 1: GSK2857916 2.50 mg/kg [ Time Frame: Pre-dose and EOI of Day 1 (Cycle 1) ]
    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods.

  3. Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM- Part 1 [ Time Frame: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1) ]
    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods. NA indicates that geometric coefficient of variation could not be calculated for a single participant.

  4. AUC[0-tau] of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM- Part 1: GSK2857916 2.50 mg/kg [ Time Frame: Pre-dose and EOI of Day 1 (Cycle 1) ]
    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods.

  5. Area Under the Concentration-time Curve From Zero to Time of Last Quantifiable Concentration (AUC[0-tlast]) of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM- Part 1 [ Time Frame: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1) ]
    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods. NA indicates that geometric coefficient of variation could not be calculated for a single participant.

  6. AUC[0-tlast]) of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM- Part 1: GSK2857916 2.50 mg/kg [ Time Frame: Pre-dose and EOI of Day 1 (Cycle 1) ]
    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods.

  7. Clearance (CL) of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1 [ Time Frame: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1) ]
    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods. NA indicates that geometric coefficient of variation could not be calculated for a single participant.

  8. CL of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1: GSK2857916 2.50 mg/kg [ Time Frame: Pre-dose and EOI of Day 1 (Cycle 1) ]
    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods.

  9. Maximum Observed Concentration (Cmax) of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1 [ Time Frame: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1) ]
    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods. NA indicates that geometric coefficient of variation could not be calculated for a single participant.

  10. Cmax of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1: GSK2857916 2.50 mg/kg [ Time Frame: Pre-dose and EOI of Day 1 (Cycle 1) ]
    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods.

  11. Trough Plasma Concentration (Ctrough) of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1 [ Time Frame: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1), Pre-dose and EOI of Day 1 (Cycle 2 and Cycle 4) ]
    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods. NA indicates that the geometric mean and geometric coefficient of variation could not be calculated since the concentration was not quantifiable. NA indicates that geometric coefficient of variation could not be calculated for a single participant.

  12. Ctrough of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1: GSK2857916 2.50 mg/kg [ Time Frame: Pre-dose and EOI of Day 1 (Cycle 1, Cycle 2 and Cycle 4) ]
    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods.

  13. Terminal Half-life (t1/2) of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1 [ Time Frame: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1) ]
    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods. NA indicates that geometric coefficient of variation could not be calculated for a single participant.

  14. t1/2 of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1: GSK2857916 2.50 mg/kg [ Time Frame: Pre-dose and EOI of Day 1 (Cycle 1) ]
    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods.

  15. Volume of Distribution at Steady State (Vss) of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1 [ Time Frame: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1) ]
    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods. NA indicates that geometric coefficient of variation could not be calculated for a single participant.

  16. Vss of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1: GSK2857916 2.50 mg/kg [ Time Frame: Pre-dose and EOI of Day 1 (Cycle 1) ]
    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods.

  17. Time to Reach Maximum Observed Concentration (Tmax) of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1 [ Time Frame: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1) ]
    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods. Median and full range of Tmax have been presented.

  18. Tmax of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1: GSK2857916 2.50 mg/kg [ Time Frame: Pre-dose and EOI of Day 1 (Cycle 1) ]
    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods. Median and full range of Tmax have been presented.

  19. Ctrough of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM-Part 2 [ Time Frame: Pre-dose and EOI of Day 1 (Cycle 1, Cycle 2 and Cycle 4) ]
    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods.

  20. AUC(0-tlast) of Cys Monomethyl Auristatin F (Cys-mcMMAF) Following IV Dose of GSK2857916 in Participants With Relapsed/Refractory MM- Part 1 [ Time Frame: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1) ]
    Blood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods. NA indicates that geometric coefficient of variation could not be calculated for a single participant.

  21. AUC(0-tlast) of Cys-mcMMAF Following IV Dose of GSK2857916 in Participants With Relapsed/Refractory MM- Part 1: GSK2857916 2.50 mg/kg [ Time Frame: Pre-dose and EOI of Day 1 (Cycle 1) ]
    Blood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods.

  22. Cmax of Cys-mcMMAF Following IV Dose of GSK2857916 in Participants With Relapsed/Refractory MM- Part 1 [ Time Frame: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1) ]
    Blood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods. NA indicates that geometric coefficient of variation could not be calculated for a single participant.

  23. Cmax of Cys-mcMMAF Following IV Dose of GSK2857916 in Participants With Relapsed/Refractory MM- Part 1: GSK2857916 2.50 mg/kg [ Time Frame: Pre-dose and EOI of Day 1 (Cycle 1) ]
    Blood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods.

  24. Ctrough of Cys-mcMMAF Following IV Dose of GSK2857916 in Participants With Relapsed/Refractory MM- Part 1 [ Time Frame: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1), Pre-dose and EOI of Day 1 (Cycle 2 and Cycle 4) ]
    Blood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods. NA indicates that the geometric mean and geometric coefficient of variation could not be calculated since the concentration was not quantifiable.

  25. Ctrough of Cys-mcMMAF Following IV Dose of GSK2857916 in Participants With Relapsed/Refractory MM- Part 1: GSK2857916 2.50 mg/kg [ Time Frame: Pre-dose and EOI of Day 1 (Cycle 1, Cycle 2 and Cycle 4) ]
    Blood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods. NA indicates that the geometric mean and geometric coefficient of variation could not be calculated since the concentration was not quantifiable.

  26. Tmax of Cys-mcMMAF Following IV Dose of GSK2857916 in Participants With Relapsed/Refractory MM- Part 1 [ Time Frame: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1) ]
    Blood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods. Median and full range of Tmax have been presented.

  27. Tmax of Cys-mcMMAF Following IV Dose of GSK2857916 in Participants With Relapsed/Refractory MM-Part 1: GSK2857916 2.50 mg/kg [ Time Frame: Pre-dose and EOI of Day 1 (Cycle 1) ]
    Blood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods. Median and full range of Tmax have been presented.

  28. Number of Participants With at Least One Confirmed Positive Post-Baseline Anti-drug Antibody Result- Part 1 [ Time Frame: Up to 21.6 months (maximum duration of follow-up from first dose to last contact or death) ]
    Serum samples were collected for the determination of anti-GSK2857916 antibodies (ADA) using a validated electrochemiluminescent (ECL) immunoassay. The assay involved screening, confirmation and titration steps. If serum samples contained ADA, they were further analyzed for the specificity of antibodies by a confirmation assay. Confirmed positive samples were titrated to obtain the titers of antibodies. The number of participants with at least one confirmed positive ADA at any time post-Baseline is presented.

  29. Number of Participants With at Least One Confirmed Positive Post-Baseline Anti-drug Antibody Result- Part 2 [ Time Frame: Up to 24.2 months (maximum duration of follow-up from first dose to last contact or death) ]
    Serum samples were collected for the determination of anti-GSK2857916 antibodies (ADA) using a validated ECLimmunoassay. The assay involved screening, confirmation and titration steps. If serum samples contained ADA, they were further analyzed for the specificity of antibodies by a confirmation assay. Confirmed positive samples were titrated to obtain the titers of antibodies. The number of participants with at least one confirmed positive ADA at any time post-Baseline is presented.

  30. Number of Participants With Antibodies to GSK2857916 in Serum Over Time- Part 1 [ Time Frame: Baseline, Day 1 (Cycle 2, 3, 4, 6, 9, 12, 16), End of study (within 30 days [+ 7 days of last treatment or prior to the start of new anti-cancer treatment], whichever is earlier) (1 cycle=21 days) ]
    Serum samples were collected for the determination of ADA using a validated ECL immunoassay. The assay involved screening, confirmation and titration steps. If serum samples contained ADA, they were further analyzed for the specificity of antibodies by a confirmation assay. Confirmed positive (pos) samples were titrated to obtain the titers of antibodies. The number of participants with screening, confirming and negative (neg) conclusive ADA results at Baseline and different timepoints is presented.

  31. Number of Participants With Antibodies to GSK2857916 in Serum Over Time- Part 2 [ Time Frame: Baseline, Day 1 (Cycle 2, 3, 6, 7, 9, 11, 12, 16), End of study (within 30 days [+ 7 days of last treatment or prior to the start of new anti-cancer treatment], whichever is earlier) (1 cycle=21 days) ]
    Serum samples were collected for the determination of ADA using a validated ECL immunoassay. The assay involved screening, confirmation and titration steps. If serum samples contained ADA, they were further analyzed for the specificity of antibodies by a confirmation assay. Confirmed positive samples were titrated to obtain the titers of antibodies. The number of participants with screening, confirming and negative conclusive ADA results at Baseline and different timepoints is presented.

  32. Overall Response Rate (ORR)- Part 1 [ Time Frame: From the Start of Treatment (at First Dose) up to the earlier of disease progression or the start of new anti-cancer therapy (maximum duration of follow-up is 21.6 months) ]
    ORR was determined by the investigator according to international myeloma working group uniform response criteria for MM (IMWG 2011). ORR was calculated as the number of participants with best overall response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) and partial response (PR).

  33. ORR-Part 2 [ Time Frame: From the Start of Treatment (at First Dose) up to the earlier of disease progression or the start of new anti-cancer therapy (maximum duration of follow-up is 24.2 months) ]
    ORR was determined by the investigator according to IMWG 2011 uniform response criteria for MM. ORR was calculated as the number of participants with best overall response of sCR, CR, VGPR and PR.

  34. Clinical Benefit Rate (CBR)- Part 1 [ Time Frame: From the Start of Treatment (at First Dose) up to the earlier of disease progression or the start of new anti-cancer therapy (maximum duration of follow-up is 21.6 months) ]
    CBR was calculated as the number of participants with best overall response of sCR, CR, VGPR, PR and minimal response (MR).

  35. CBR- Part 2 [ Time Frame: From the Start of Treatment (at First Dose) up to the earlier of disease progression or the start of new anti-cancer therapy (maximum duration of follow-up is 24.2 months) ]
    CBR was calculated as the number of participants with best overall response of sCR, CR, VGPR, PR and MR.



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.


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Ages Eligible for Study:   18 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, 18 years or older (at the time consent is obtained)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Part 1/dose escalation; Histologically or cytologically confirmed diagnosis of Multiple Myeloma in a subject who fulfills all of the following: has undergone stem cell transplant, or is considered transplant ineligible, has been pretreated with at least the 3 following classes of anti-myeloma drugs: alkylators, proteasome inhibitors and immunomodulators, has demonstrated progression on, or within 60 days of completion of the last therapy.

Part 2 /MM cohort; Histologically or cytologically confirmed diagnosis of: Multiple Myeloma in a subject who fulfills all of the following: has undergone stem cell transplant, or is considered transplant ineligible, has been pretreated with at least the 3 following classes of anti-myeloma drugs: alkylators, proteasome inhibitors and immunomodulators, has demonstrated progression on, or within 60 days of completion of the last therapy, and has measurable disease with at least one of the following: serum M-protein >=0.5 gram (g)/decilitre (dL) (>=5 g/Litre (L)), urine M-protein >=200 milligram (mg)/24hour (h).

Serum free light chain (FLC) assay: Involved FLC level >=5 mg/dL (>=50 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65) and biopsy proven plasmacytoma (should be measured within 28 days of Screening Visit).

  • Part 2/Other BCMA positive Hematologic Malignancies cohort: Subject with one of the following lymphomas: Diffuse Large B-cell Lymphoma (DLBCL) or follicular lymphoma (FL) that exhibits positive BCMA expression on tumor cells as determined by a central laboratory using a validated Immunohistochemistry (IHC) assay. Eligible subjects with BCMA positive malignancies must also fulfill the prior treatment requirements as follows: DLBCL: at least 2 prior lines of systemic therapy containing at least one line of chemo-immunotherapy with anti-CD20 antibody, and either has undergone stem cell transplant or is considered transplant ineligible. FL: at least 2 prior lines of systemic therapy.
  • Subjects 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; subject meets the remainder of the eligibility criteria outlined in the study protocol.
  • Adequate organ system functions as defined below Absolute neutrophil count>=1.0x10^9/L, hemoglobin>=8.0 g/dL, platelet>=50x10^9/L, international normalized ration (INR) <=1.5, Partial thromboplastin time <=1.5xupper limit of normal (ULN), total bilirubin <=1.25xULN, alanine aminotransferase and aspartate aminotransferase<=1.5 X ULN, serum creatinine or calculated creatinine clearance<1.2XULN >=60 mL/min for Part 1;>=50 mL/minute (min) for Part 2 if data supports loosening criteria, Albuminuria<=500 mg/24h, left ventricular ejection fraction >=50%, Troponin<=1xULN, Calcium<=1.1xULN
  • A female subject is eligible to participate if she is of: Non-childbearing potential or women of childbearing potential must have a negative serum pregnancy test within 72 hours of first dose of study treatment and agree to use effective contraception during the study and for 60 days following the last dose of study treatment.
  • Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception from the time of first dose of study until 60 days after the last dose of study treatment to allow for clearance of any altered sperm
  • All prior treatment-related toxicities (defined by National Cancer Institute- Common Toxicity Criteria for Adverse Events, version 4) must be <=Grade 1 at the time of enrollment except for alopecia, and grade 2 neuropathy.

Exclusion Criteria:

  • Systemic anti-tumor therapy within 14 days, or plasmapheresis within 7 days prior to the first dose of study drug
  • Use of an investigational drug within 14 days or five half-lives, whichever is shorter, preceding the first dose of study drug. Prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study drug.
  • History of an allogeneic stem cell transplant. Subjects with a history of an autologous stem cell transplant are NOT excluded if they meet inclusion criteria related to history of autologous stem cell transplant.
  • Presence of active renal condition (infection, requirement for dialysis or any other condition that could affect subject's safety). Subjects with isolated proteinuria resulting from MM are eligible, provided they fulfil the inclusion criteria related to organ system function.
  • Evidence of active mucosal or internal bleeding
  • Any major surgery within the last four weeks.
  • Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions (including lab abnormalities) that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures.
  • Known active infection requiring antibiotic treatment
  • Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, hepatic, renal or cardiac disease
  • Subjects with previous or concurrent malignancies are allowed only if the second tumor is not contributing to the subject's illness. The subject must not be receiving active therapy, other than hormonal therapy for this disease and the disease must be considered medically stable for at least 2 years.
  • Evidence of cardiovascular risk including any of the following: QT interval corrected>=470 millisecond, evidence of current clinically significant uncontrolled arrhythmias, history of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within six months of Screening, Class III or IV heart failure as defined by the New York Heart Association functional classification system, uncontrolled hypertension, subjects with intra-cardiac defibrillators or permanent pacemakers, abnormal cardiac valve morphology (>=grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study). Subjects with moderate valvular thickening should not be entered on study.
  • 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.
  • Known human immuno virus infection.
  • Subjects with positive test for Hepatitis B surface (HBS-Ag) or Hepatitis B core (HBc)antigen
  • Subjects with positive test for hepatitis C (HCV) infection are excluded regardless of viral load. If hepatitis C antibody test is positive, a confirmatory polymerase chain reaction (PCR) or Recombinant immunoblot assay (RIBA) test should be performed. If the PCR or RIBA test is negative, subject is eligible for this trial
  • Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per investigator's assessment).
  • Current corneal disease or a history of corneal disease.

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): NCT02064387


Locations
Layout table for location information
United States, Massachusetts
GSK Investigational Site
Boston, Massachusetts, United States, 02215
United States, New York
GSK Investigational Site
New York, New York, United States, 10065
United States, North Carolina
GSK Investigational Site
Chapel Hill, North Carolina, United States, 27599-7600
United States, Pennsylvania
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
GSK Investigational Site
Dallas, Texas, United States, 75390-8565
United States, Washington
GSK Investigational Site
Seattle, Washington, United States, 98109
Canada, British Columbia
GSK Investigational Site
Vancouver, British Columbia, Canada, V5Z 1M9
Canada, Ontario
GSK Investigational Site
Toronto, Ontario, Canada, M5G 2M9
United Kingdom
GSK Investigational Site
London, United Kingdom, NW1 2BU
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
  Study Documents (Full-Text)

Documents provided by GlaxoSmithKline:
Study Protocol  [PDF] November 2, 2017
Statistical Analysis Plan  [PDF] November 6, 2018

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02064387    
Other Study ID Numbers: 117159
2013-004549-18 ( EudraCT Number )
First Posted: February 17, 2014    Key Record Dates
Results First Posted: September 26, 2019
Last Update Posted: September 26, 2019
Last Verified: August 2019
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 is available via the Clinical Study Data Request site (click on the link provided below)
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: https://www.clinicalstudydatarequest.com/SearchAllPostings.aspx?searchparam=117159
Keywords provided by GlaxoSmithKline:
Multiple Myeloma
BCMA expressing Lymphomas
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