A Study to Investigate the Efficacy and Safety of Two Doses of GSK2857916 in Participants With Multiple Myeloma Who Have Failed Prior Treatment With an Anti-CD38 Antibody

Sponsor
GlaxoSmithKline (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03525678
Collaborator
(none)
221
Enrollment
59
Locations
3
Arms
45.4
Anticipated Duration (Months)
3.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Multiple myeloma (MM) is an incurable malignancy and accounts for 1 percentage (%) of all cancers and for 10% of all hematologic malignancies. Participants with relapsed/refractory multiple myeloma (RRMM) will be included in this study, to evaluate the efficacy and safety of belantamab mafodotin (GSK2857916) monotherapy. Participants will be treated with belantamab mafodotin monotherapy until disease progression (PD) or unacceptable toxicity and will be followed for Progression Free Survival and Overall survival. The participants will be randomized to receive either frozen belantamab mafodotin at the dose of 2.5 milligram per kilogram (mg/kg) or 3.4 mg/kg administered Intravenously (IV). There will be an independent cohort of participants who will receive a lyophilized configuration of belantamab mafodotin. For participants who discontinued from the study other than Progressive disease (PD), disease evaluation will continue to be performed at 3-week intervals until confirmed PD, death, start of a new anticancer treatment, withdrawal of consent, or end of the study whichever occurs first.

Condition or DiseaseIntervention/TreatmentPhase
  • Drug: Belantamab mafodotin frozen liquid
  • Drug: Belantamab mafodotin lyophilized powder
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
221 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II, Open Label, Randomized, Two-Arm Study to Investigate the Efficacy and Safety of Two Doses of the Antibody Drug Conjugate GSK2857916 in Participants With Multiple Myeloma Who Had 3 or More Prior Lines of Treatment, Are Refractory to a Proteasome Inhibitor and an Immunomodulatory Agent and Have Failed an Anti-CD38 Antibody (DREAMM 2)
Actual Study Start Date :
Jun 18, 2018
Actual Primary Completion Date :
Jun 21, 2019
Anticipated Study Completion Date :
Mar 31, 2022

Arms and Interventions

ArmIntervention/Treatment
Experimental: Participants receiving frozen 2.5 mg/kg belantamab mafodotin

Participants will receive 2.5 mg/kg frozen liquid belantamab mafodotin. Participants will be administered with frozen liquid belantamab mafodotin via infusion pump every 3 weeks.

Drug: Belantamab mafodotin frozen liquid
Belantamab mafodotin will be available as frozen liquid. Frozen liquid will be available as 30 milligram (mg)/vial solution in a single use vial with unit dose strength of 2.5 or 3.4 mg/kg. Belantamab mafodotin will be administered as IV solution over at least 30 minutes. Frozen belantamab mafodotin will be diluted in 0.9 percent saline and administered via infusion pump.

Experimental: Participants receiving frozen 3.4 mg/kg belantamab mafodotin

Participants will receive 3.4 mg/kg frozen liquid belantamab mafodotin. Participants will be administered with frozen liquid belantamab mafodotin via infusion pump every 3 weeks.

Drug: Belantamab mafodotin frozen liquid
Belantamab mafodotin will be available as frozen liquid. Frozen liquid will be available as 30 milligram (mg)/vial solution in a single use vial with unit dose strength of 2.5 or 3.4 mg/kg. Belantamab mafodotin will be administered as IV solution over at least 30 minutes. Frozen belantamab mafodotin will be diluted in 0.9 percent saline and administered via infusion pump.

Experimental: Participants receiving lyophilized belantamab mafodotin

Participants in lyophilized arm will receive lyophilized belantamab mafodotin once lyophilized configuration becomes available and enrollment has been completed for frozen liquid arms.

Drug: Belantamab mafodotin lyophilized powder
Belantamab mafodotin will be available as lyophilized powder. Lyophilized powder will be available as 100 mg/vial in single-use vial for reconstitution with unit dose strength of 3.4 mg/kg. Lyophilized belantamab mafodotin will be reconstituted using water for injection and diluted with saline before use.

Outcome Measures

Primary Outcome Measures

  1. Overall Response Rate (ORR) by Independent Review Committee (IRC) (Full Analysis Population) [Up to 48 weeks]

    ORR was determined according to the 2016 international myeloma working group (IMWG) response criteria by IRC. ORR was calculated as the percentage of participants with a confirmed partial response (PR) or better (that is [i.e.], PR, very good partial response [VGPR], complete response [CR] and stringent complete response [sCR]). Confidence intervals were based on the exact method.

  2. Overall Response Rate by Independent Review Committee (Efficacy Population) [Up to 48 weeks]

    ORR was determined according to the 2016 IMWG response criteria by IRC. ORR was calculated as the percentage of participants with a confirmed PR or better (i.e., PR, VGPR, CR and sCR). Confidence intervals were based on the exact method. Efficacy Population comprised of first 130 intent-to-treat participants whether or not randomized treatment (frozen solution) was administered. Intent-to-treat Population comprised of all randomized participants whether or not randomized treatment was administered.

Secondary Outcome Measures

  1. Overall Response Rate by Investigator Assessment (IA) (Full Analysis Population) [Up to 48 weeks]

    ORR was determined by the investigator according to the 2016 IMWG response criteria. ORR was calculated as the percentage of participants with a confirmed PR or better (i.e., PR, VGPR, CR and sCR). Confidence intervals were based on the exact method.

  2. Overall Response Rate by Investigator Assessment (Efficacy Population) [Up to 48 weeks]

    ORR was determined by the investigator according to the 2016 IMWG response criteria. ORR was calculated as the percentage of participants with a confirmed PR or better (i.e., PR, VGPR, CR and sCR). Confidence intervals were based on the exact method.

  3. Clinical Benefit Rate (CBR) by Investigator Assessment (Full Analysis Population) [Up to 48 weeks]

    CBR was determined by the investigator according to the 2016 IMWG response criteria. CBR was calculated as the percentage of participants with a confirmed minimal response (MR) or better (i.e., MR, PR, VGPR, CR and sCR). Confidence intervals were based on the exact method.

  4. Clinical Benefit Rate by Investigator Assessment (Efficacy Population) [Up to 48 weeks]

    CBR was determined by the investigator according to the 2016 IMWG response criteria. CBR was calculated as the percentage of participants with a confirmed MR or better (i.e., MR, PR, VGPR, CR and sCR). Confidence intervals were based on the exact method.

  5. Clinical Benefit Rate by Independent Review Committee (Full Analysis Population) [Up to 48 weeks]

    CBR was determined according to the 2016 IMWG response criteria by IRC. CBR was calculated as the percentage of participants with a confirmed MR or better (i.e., MR, PR, VGPR, CR and sCR). Confidence intervals were based on the exact method.

  6. Clinical Benefit Rate by Independent Review Committee (Efficacy Population) [Up to 48 weeks]

    CBR was determined according to the 2016 IMWG response criteria by IRC. CBR was calculated as the percentage of participants with a confirmed MR or better (i.e., MR, PR, VGPR, CR and sCR). Confidence intervals were based on the exact method.

  7. Duration of Response (DoR) by Investigator Assessment (Full Analysis Population) [Up to 48 weeks]

    DoR is defined as the time from first documented evidence of PR or better until the earliest date of documented disease progression (PD) per IMWG response criteria; or death due to PD among participants who achieved an overall response, i.e., confirmed PR or better. DOR based on responses assessed by investigator is presented. Median and inter-quartile range (first quartile and third quartile) of DOR are presented.

  8. Duration of Response by Investigator Assessment (Efficacy Population) [Up to 48 weeks]

    DoR is defined as the time from first documented evidence of PR or better until the earliest date of documented PD per IMWG response criteria; or death due to PD among participants who achieved an overall response, i.e., confirmed PR or better. DOR based on responses assessed by investigator is presented. Median and inter-quartile range (first quartile and third quartile) of DOR are presented.

  9. Duration of Response by Independent Review Committee (Full Analysis Population) [Up to 48 weeks]

    DoR is defined as the time from first documented evidence of PR or better until the earliest date of documented PD per IMWG response criteria; or death due to PD among participants who achieved an overall response, i.e., confirmed PR or better. DOR based on responses assessed by IRC is presented. Median and inter-quartile range (first quartile and third quartile) of DOR are presented.

  10. Duration of Response by Independent Review Committee (Efficacy Population) [Up to 48 weeks]

    DoR is defined as the time from first documented evidence of PR or better until the earliest date of documented PD per IMWG response criteria; or death due to PD among participants who achieved an overall response, i.e., confirmed PR or better. DOR based on responses assessed by IRC is presented. Median and inter-quartile range (first quartile and third quartile) of DOR are presented.

  11. Time to Response by Investigator Assessment (Full Analysis Population) [Up to 48 weeks]

    Time to response is defined as the time between the date of randomization and the first documented evidence of response (PR or better), among participants who achieve a response (i.e., confirmed PR or better). Time to response based on responses assessed by investigator is presented. Median and inter-quartile range (first quartile and third quartile) of time to response are presented.

  12. Time to Response by Investigator Assessment (Efficacy Population) [Up to 48 weeks]

    Time to response is defined as the time between the date of randomization and the first documented evidence of response (PR or better), among participants who achieve a response (i.e., confirmed PR or better). Time to response based on responses assessed by investigator is presented. Median and inter-quartile range (first quartile and third quartile) of time to response are presented.

  13. Time to Response by Independent Review Committee (Full Analysis Population) [Up to 48 weeks]

    Time to response is defined as the time between the date of randomization and the first documented evidence of response (PR or better), among participants who achieve a response (i.e., confirmed PR or better). Time to response based on responses assessed by IRC is presented. Median and inter-quartile range (first quartile and third quartile) of time to response are presented.

  14. Time to Response by Independent Review Committee (Efficacy Population) [Up to 48 weeks]

    Time to response is defined as the time between the date of randomization and the first documented evidence of response (PR or better), among participants who achieve a response (i.e., confirmed PR or better). Time to response based on responses assessed by IRC is presented. Median and inter-quartile range (first quartile and third quartile) of time to response are presented.

  15. Progression Free Survival by Investigator Assessment [Up to 48 weeks]

    Progression free survival is defined as the time from randomization until the earliest date of documented PD per IMWG, or death due to any cause. Progression free survival based on responses assessed by investigator is presented. Median and inter-quartile range (first quartile and third quartile) of progression free survival are presented.

  16. Progression Free Survival by Independent Review Committee [Up to 48 weeks]

    Progression free survival is defined as the time from randomization until the earliest date of documented PD per IMWG, or death due to any cause. Progression free survival based on responses assessed by IRC is presented. Median and inter-quartile range (first quartile and third quartile) of progression free survival are presented.

  17. Time to Progression by Investigator Assessment [Up to 48 weeks]

    Time to progression is defined as the time from randomization until the earliest date of documented PD per IMWG, or death due to PD. Time to Progression based on responses assessed by investigator is presented. Median and inter-quartile range (first quartile and third quartile) of time to progression are presented.

  18. Time to Progression by Independent Review Committee [Up to 48 weeks]

    Time to progression is defined as the time from randomization until the earliest date of documented PD per IMWG, or death due to PD. Time to Progression based on responses assessed by IRC is presented. Median and inter-quartile range (first quartile and third quartile) of time to progression are presented.

  19. Overall Survival [Up to 48 weeks]

    Overall survival is defined as the time from randomization until death due to any cause. Overall survival was analyzed using the Kaplan-Meier method by dose level. Median and inter-quartile range (first quartile and third quartile) of overall survival are presented.

  20. Number of Participants With Change From Baseline in Hematology Parameters With Respect to the Normal Range [Baseline (Day 1) and Up to 48 weeks]

    Following parameters were assessed:basophils(Baso),eosinophils(Eosino),hematocrit(Hct),mean corpuscular hemoglobin(MCH),MCH concentration(MCHC),MC volume(MCV),monocyte(Mono),erythrocytes(Erythro),reticulocytes(Reticu).Baseline is latest pre-dose assessment(Day1)with a non-missing value, including unscheduled visits.Data was categorized as decrease to low(value below lower limit of normal range[LNR]),increase to high(value above upper LNR),change to normal/no change(NC).If values were unchanged(eg.high to high) or whose value became normal,were recorded in change to normal/NC category.Participants were counted twice if participant had both decreased to low/increased to high during post-Baseline(PB).Data for worst case PB is presented.Full Safety Population(FSP) comprised of all participants who received at least 1dose of study drug(frozen liquid or lyophilized powder). 3 out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population.

  21. Number of Participants With Grade Change From Baseline in Hematology Parameters [Baseline (Day 1) and Up to 48 weeks]

    Blood samples were collected for the analysis of following hematology parameters: hemoglobin (Hb), lymphocyte count (Lymph), neutrophil count (Neutro), platelet count (PC), and leukocyte count (leuko). The laboratory parameters were graded according to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as latest pre-dose assessment (Day 1) 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. Only those participants with increase to grade 3 and increase to grade 4 have been presented.

  22. Number of Participants With Change From Baseline in Clinical Chemistry Parameters With Respect to the Normal Range [Baseline (Day 1) and Up to 48 weeks]

    Blood samples were collected for analysis of clinical chemistry parameters: bicarbonate, direct bilirubin(D.Bil), calcium, chloride, lactate dehydrogenase(LDH), total protein, urea or blood urea nitrogen(BUN),estimated glomerular filtration rate (eGFR).Baseline is latest pre-dose assessment(Day 1) with a non-missing value, including unscheduled visits. Number of participants with worst case clinical chemistry change from Baseline with respect to normal range are presented. Data was categorized as decrease to low (value below the lower LNR), increase to high (value above the upper LNR) and change to normal or NC. If values were unchanged (example: high to high), or whose value became normal, were recorded in the change to normal or NC category. Participants were counted twice if the participant had both decreased to low and increased to high during post Baseline. 3 out of 221participants did not receive any study treatment, were excluded from FSP.

  23. Number of Participants With Grade Change From Baseline in Clinical Chemistry Parameters [Baseline (Day 1) and Up to 48 weeks]

    Blood samples were collected for analysis of clinical chemistry parameters: glucose(Gl), albumin, alkaline phosphatase (ALP), alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bilirubin(T.Bil), creatinine kinase (CK), creatinine, gamma glutamyl transferase (GGT), potassium (Pot), magnesium (Mg), sodium (Sod), phosphate (Ph) and urate. Values (Hyper and hypo) for Gl, Pot, Mg and Sod is presented. Laboratory parameters were graded according to NCI-CTCAE version 4.03. Grade1: mild; Grade2: moderate; Grade3: severe or medically significant; Grade4: life-threatening consequences. Baseline is latest pre-dose assessment(Day 1) 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 PB is presented. Only those participants with increase to grade3 and increase to grade4 have been presented. 3 out of 221participants did not receive any study treatment, were excluded from FSP.

  24. Number of Participants With Abnormal Findings During Physical Examination [Up to 48 weeks]

    Physical examination included assessment of the head, eyes, ears, nose, throat, skin, thyroid, lungs, cardiovascular, abdomen (liver and spleen), lymph nodes, and extremities. This analysis was planned, but data was not collected and captured in the database.

  25. Number of Participants With Change From Baseline in Pulse Rate [Baseline (Day 1) and Up to 48 weeks]

    Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. Number of participants with worst case change from Baseline in pulse rate is presented. Data is categorized as: pulse rate 'decrease to <60 beats per minute [bpm]', 'increase to >100 bpm' and 'change to normal or no change'. If values were unchanged (example: increase to >100 bpm to increase to >100 bpm), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to <60 bpm' and 'increased to >100 bpm' during post Baseline. Data for worst-case post Baseline is presented.

  26. Number of Participants With Change From Baseline in Body Temperature [Baseline (Day 1) and Up to 48 weeks]

    Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. Number of participants with worst case change from Baseline in body temperature are presented. Data is categorized as: body temperature 'decrease to <=35 degrees celsius', 'increase to >=38 degrees celsius' and 'change to normal or no change'. If values were unchanged (example: increase to >=38 to increase to >=38 degrees celsius), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to <=35' and 'increased to >=38 degrees celsius' during post Baseline. Data for worst-case post Baseline is presented.

  27. Number of Participants With Grade Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) [Baseline (Day 1) and Up to 48 weeks]

    SBP and DBP were graded using NCI CTCAE version 4.03. For SBP: Grade 0: <120 millimeter mercury (mmHg); Grade 1: 120-139 mmHg; Grade 2: 140-159 mmHg; Grade 3: >=160 mmHg. For DBP: Grade 0: <80 mmHg; Grade 1: 80-89 mmHg; Grade 2: 90-99 mmHg; Grade 3: >=100 mmHg. Baseline was defined as the latest pre-dose assessment (Day 1) 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. Only those participants with increase to grade 2 and increase to grade 3 have been presented.

  28. Number of Participants With Serious Adverse Events (SAEs), Common (>=5%) Non-serious Adverse Events and Adverse Events of Special Interest (AESI) [Up to 48 weeks]

    An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that; results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician, is associated with liver injury and impaired liver function. Number of participants who had SAEs and common (>=5%) non-SAEs are presented. Number of participants with AESI (keratopathy, dry eye events, blurred vision, thrombocytopenia, infusion-related reactions, corneal events and neutropenia) are also presented.

  29. Number of Participants With Change From Baseline in Best Corrected Visual Acuity (BCVA) Test Scores [Baseline (Day 1) and Up to 48 weeks]

    Baseline was defined as latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. BCVA score was assessed individually for each eye. BCVA test scores were categorized as no change/improved vision, possible worsened vision and definite worsened vision. No change/improved vision was defined as a change from Baseline <0.12 Logarithm of the Minimum Angle of Resolution (logMAR) score; a possible worsened vision was defined as a change from Baseline >=0.12 to <0.3 logMAR score; a definite worsened vision was defined as a change from Baseline >=0.3 logMAR score. Data for worst-case change from Baseline is presented. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population.

  30. Number of Participants With Intraocular Pressure (IOP) >=22 mmHg Anytime Post-Baseline [Up to 48 weeks]

    Baseline was defined as latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. IOP was assessed individually for each eye. Number of participants with IOP >=22 mmHg anytime post-Baseline are presented. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population.

  31. Number of Participants With Shift in Pupillary Examination Findings From Normal (Baseline) to Abnormal (Worst Post-Baseline) [Baseline and Up to 48 weeks]

    Baseline was defined as latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. Number of participants with shift in pupillary examination findings from normal (Baseline) to abnormal (worst post-Baseline) are presented.

  32. Number of Participants With Shift in Extraocular Muscle Movement From Yes (Baseline) to no (Worst Post-Baseline) [Baseline and Up to 48 weeks]

    Baseline was defined as latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. Extraocular muscle movement was assessed individually for each eye. Number of participants with shift in extraocular muscle movement from yes (Baseline) to no (worst post-Baseline) are presented. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population.

  33. Number of Participants With Shift in Corneal Epithelium Findings From Normal (Baseline) to Abnormal (Worst Post-Baseline) for Corneal Epithelium (CE) and Corneal Stroma (CS) [Baseline and Up to 48 weeks]

    Baseline was defined as latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. Corneal epithelium findings for CE and CS were assessed individually for each eye. Number of participants with shift in corneal epithelium findings from normal (Baseline) to abnormal (worst post-Baseline) for CE and CS are presented. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population.

  34. Number of Participants With Shift in Corneal Epithelium Findings From no (Baseline) to Yes (Worst Post-Baseline) [Baseline and Up to 48 weeks]

    Baseline was defined as latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. Corneal epithelium findings like active edema, active opacity, corneal neovascularization (CN), corneal ulcer, epithelial microcystic edema (EME) and subepithelial were performed using a slit lamp. Number of participants with shift in corneal epithelium findings from no (Baseline) to yes (worst post-Baseline) are presented. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population.

  35. Number of Participants With Shift in Tear Break-up Time From >10 Seconds (Baseline) to <=5 Seconds (Worst Post-Baseline) [Baseline and Up to 48 weeks]

    Baseline was defined as latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. Number of participants with shift in tear break-up time from >10 seconds (Baseline) to <=5 seconds (worst post-Baseline) are presented. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population.

  36. Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC[0-infinity]) of GSK2857916 Following IV Dose in Participants With RRMM [Cycle 1 and Cycle 3: Pre-dose, end of infusion (EOI), 2 hours and 24 hours post start of infusion (SOI) on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)]

    Blood samples were collected at designated timepoints. Pharmacokinetic (PK) parameters of GSK2857916 were calculated using non-compartmental methods. Full Pharmacokinetic (PK) Population comprised of all participants in the Full Safety Population who had atleast 1 non-missing PK assessment.

  37. Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK2857916 Following IV Dose in Participants With RRMM [Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)]

    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods.

  38. 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 RRMM [Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)]

    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods.

  39. Maximum Observed Concentration (Cmax) of GSK2857916 Following IV Dose in Participants With RRMM [Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)]

    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods.

  40. Time to Reach Maximum Observed Concentration (Tmax) of GSK2857916 Following IV Dose in Participants With RRMM [Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)]

    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods.

  41. Terminal Half-life (t1/2) of GSK2857916 Following IV Dose in Participants With RRMM [Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)]

    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods.

  42. AUC(0-infinity) of GSK2857916 Total Antibody Following IV Dose in Participants With RRMM [Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)]

    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 total antibody were calculated using non-compartmental methods.

  43. AUC(0-tau) of GSK2857916 Total Antibody Following IV Dose in Participants With RRMM [Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)]

    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 total antibody were calculated using non-compartmental methods.

  44. AUC(0-tlast) of GSK2857916 Total Antibody Following IV Dose in Participants With RRMM [Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)]

    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 total antibody were calculated using non-compartmental methods.

  45. Cmax of GSK2857916 Total Antibody Following IV Dose in Participants With RRMM [Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)]

    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 total antibody were calculated using non-compartmental methods.

  46. Tmax of GSK2857916 Total Antibody Following IV Dose in Participants With RRMM [Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)]

    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 total antibody were calculated using non-compartmental methods.

  47. t1/2 of GSK2857916 Total Antibody Following IV Dose in Participants With RRMM [Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)]

    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 total antibody were calculated using non-compartmental methods.

  48. AUC(0-infinity) of Cysteine-maleimidocaproyl Monomethyl Auristatin F (Cys-mcMMAF) Following IV Dose of GSK2857916 in Participants With RRMM [Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)]

    Blood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods.

  49. AUC(0-tau) of Cys-mcMMAF Following IV Dose of GSK2857916 in Participants With RRMM [Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)]

    Blood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods.

  50. AUC(0-tlast) of Cysteine-maleimidocaproyl Monomethyl Auristatin F (Cys-mcMMAF) Following IV Dose of GSK2857916 in Participants With RRMM [Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)]

    Blood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods.

  51. Cmax of Cys-mcMMAF Following IV Dose of GSK2857916 in Participants With RRMM [Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)]

    Blood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods.

  52. Tmax of Cys-mcMMAF Following IV Dose of GSK2857916 in Participants With RRMM [Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)]

    Blood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods.

  53. t1/2 of Cys-mcMMAF Following IV Dose of GSK2857916 in Participants With RRMM [Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)]

    Blood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods.

  54. Number of Participants With at Least One Confirmed Positive Post-Baseline Anti-drug Antibody (ADA) Result [Up to 48 weeks]

    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 tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for the specificity using the confirmation assay. Samples that confirmed positive in the confirmation assay were reported as 'positive'. Confirmed positive ADA samples were further characterized in the titration assay to quasi-quantitate the amount of ADA in the sample. Additionally, confirmed positive ADA samples were also tested in a validated neutralizing antibody assay to determine the potential neutralizing activity of the ADA.

  55. Titers of Anti-drug Antibodies Against GSK2857916 [Up to 48 weeks]

    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. Titers of anti-drug antibodies against GSK2857916 is presented. No participant was found with positive results for ADA test in arms; GSK2857916 3.4 mg/kg (Frozen liquid) and GSK2857916 3.4 mg/kg (Lyophilized). Hence, titer values are not presented for both these arms.

  56. Number of Participants With Symptomatic AEs Measured by Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) [Up to 48 weeks]

    The PRO-CTCAE is a patient-reported outcome measure developed to evaluate symptomatic toxicity in participants on cancer clinical trials. It included symptomatic toxicities drawn from the CTCAE like blurred vision (BV), chills, constipation, decreased appetite (DA), fatigue, general pain (GP), heart palpitations (HP), mouth/throat (M/T) sores, nausea, nosebleed, shortness of breath (SB), vomiting and watery eyes (WE). Items were scored individually on a 0 to 4 scale for severity, frequency and interference. Number of participants with symptomatic AEs (those who had a maximum post-Baseline rating greater than 0, example; 1, 2, 3, or 4) measured by PRO-CTCAE are presented.

  57. Worst Change From Baseline in National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) Overall Composite Score [Baseline (Day 1) and up to Week 48]

    The NEI-VFQ-25 consisted of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question to assess the impact of ocular toxicity on visual function. Items were coded to a 0 to 100 scale and averaged to calculate domains. Domain scores ranged from 0 to 100; higher scores are better. Therefore, increase in score means improvement. Baseline was defined as latest pre-dose assessment (Day 1) 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 worst-case post Baseline is presented.

  58. Worst Change From Baseline in Ocular Surface Disease Index (OSDI) Total Score [Baseline (Day 1) and up to Week 48]

    The OSDI is a 12-item questionnaire designed to assess both the frequency of dry eye symptoms and their impact on vision-related functioning. The total OSDI score was calculated as (sum of scores for all questions answered*100) divided by (total number of questions answered*4). Domain scores ranged from 0 to 100; lower scores are better. Therefore, decrease in score from Baseline means improvement. Baseline was defined as latest pre-dose assessment (Day 1) 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 worst-case post Baseline is presented.

  59. Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core Module (EORTC QLQ-C30) Score [Baseline (Day 1) and Week 07, Week 13, Week 19, Week 25, Week 31, Week 37 and Week 43]

    The EORTC QLQ-C30 includes 30-items with single and multi-item scales. These included five functional scales (physical functioning [PF], role functioning [RF], cognitive functioning [CF], emotional functioning [EF] and social functioning [SF]), three symptom scales (fatigue, pain and nausea/vomiting [N/V]), a global health status (GHS)/ Quality-of-Life (QoL) scale, and six single items (constipation, diarrhea, insomnia, dyspnea, appetite loss [AL] and financial difficulties [FD]). Response options are 1 to 4. Scores were averaged and transformed to 0 to 100, a high score for functional scales/ GHS/QoL represent better functioning ability or health-related quality-of-life (HRQoL), whereas a high score for symptom scales/ single items represent significant symptomatology. Baseline was defined as latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

  60. Change From Baseline in EORTC QLQ 20-item Multiple Myeloma Module (MY20) Score [Baseline (Day 1) and Week 07, Week 13, Week 19, Week 25, Week 31, Week 37 and Week 43]

    The EORTC QLQ-MY20 is a supplement to the QLQ-C30 instrument used in participants with multiple myeloma. The module comprised of 20 questions that addressed four myeloma-specific HRQoL domains: disease symptoms (DS), side effects of treatment (SET), future perspective (FP) and body image (BI). Responses are 1 to 4. Scores were averaged and scales were transformed to 0 to 100 scale. A high score for disease symptoms and side effects of treatment represented a high level of symptomatology or problems, whereas a high score for future perspective and body image represented better outcomes. Baseline was defined as latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Participants who provided signed written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

  • Male or female, 18 years or older.

  • Participants with Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

  • Participants with histologically or cytologically confirmed diagnosis of MM as defined in IMWG, 2014 criteria, and participant has undergone stem cell transplant or is considered transplant ineligible and has failed at least 3 prior lines of anti-myeloma treatments, including an anti-CD38 antibody (example [e.g.], daratumumab) alone or in combination, and is refractory to an Immunomodulatory drug (IMiD) (that is [i.e.], lenalidomide or pomalidomide), and to a proteasome inhibitor (e.g., bortezomib, ixazomib or carfilzomib).

  • The participant 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 milligram per 24 hours (mg/24h); Serum Free light chain (FLC) assay:

Involved FLC level >=10 mg/dL (>=100 mg/Liter) 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 enrollment; no active infection(s); participants meet the remainder of the eligibility criteria outlined in the protocol.

  • Participants with adequate organ system functions as defined follows: Absolute neutrophil count (ANC) >=1.0 X 109/L; Hemoglobin >=8.0 g/dL; Platelets>= 50 X 109/L; Total bilirubin <=1.5X Upper limit of normal (ULN). Isolated bilirubin >=1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent); Alanine aminotransferase (ALT) <=2.5X ULN; Estimated glomerular filtration rate (eGFR) >=30 milliliter per minute per 1.73 meter square (mL/min/m^2); Spot urine (albumin/creatinine ratios [spot urine]) <500 milligram per gram (mg/g) (56 mg per millimoles [mg/mmol]); Left ventricular ejection fraction (LVEF) (Echocardiogram)>=45 percent.

  • Female participants: Contraceptive use by men or 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 breastfeeding, and not a woman of childbearing potential (WOCBP) or is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency, during the intervention period and for at least 80 days after the last dose of study intervention 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 intervention. 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 intervention. 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 or women 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 during the intervention period and for at least 140 days: Refrain from donating sperm; 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 Agree to use a male condom and female partner to use an additional highly effective contraceptive method with a failure rate of <1% per year as when having sexual intercourse with a WOCBP who is not currently pregnant.

  • 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 enrollment except for alopecia and Grade 2 peripheral neuropathy.

  • For France only: A participant will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria:
  • Systemic anti-myeloma therapy within <=14 days, or 5 half-lives, whichever is shorter, or plasmapheresis within 7 days prior to the first dose of study drug.

  • Systemic treatment with high dose steroids (equivalent to >=60 mg prednisone daily for

=4 days) within the past 14 days if administered to treat MM or non-MM disease.

  • Symptomatic amyloidosis, active 'polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes' (POEMS) syndrome, active plasma cell leukemia at the time of screening.

  • Prior allogeneic stem cell transplant.

  • Current corneal epithelial disease except mild punctate keratopathy.

  • 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 drugs. Prior B-cell maturation antigen (BCMA) targeted therapy.

  • Evidence of active mucosal or internal bleeding.

  • Any major surgery within the last four weeks.

  • Presence of active renal condition (infection, requirement for dialysis or any other condition that could affect participant's safety). Participants with isolated proteinuria resulting from MM are eligible.

  • Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions (including lab abnormalities) that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures.

  • 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.

  • 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 principal investigators and GlaxoSmithKline Medical Monitor, will not affect the evaluation of the effects of this clinical trial treatment on the currently targeted malignancy (MM). Participants with curatively treated non-melanoma skin cancer may be enrolled.

  • Evidence of cardiovascular risk including any of the following: Corrected QT interval Fridericia (QTcF) interval >480 milliseconds (msec); Evidence of current clinically significant uncontrolled arrhythmias, including clinically significant electrocardiogram abnormalities such as 2nd degree (Type II) or 3rd degree atrioventricular (AV) block; 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 (NYHA); Uncontrolled hypertension.

  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to belantamab mafodotin, or any of the components of the study treatment.

  • Pregnant or lactating female.

  • Active infection requiring antibiotic, antiviral, or antifungal treatment.

  • Known Human Immunodeficiency Virus (HIV) infection.

  • Presence of hepatitis B surface antigen (HBsAg), 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.

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1GSK Investigational SiteNew HavenConnecticutUnited States06510
2GSK Investigational SiteAtlantaGeorgiaUnited States30322
3GSK Investigational SiteAtlantaGeorgiaUnited States30342
4GSK Investigational SiteChicagoIllinoisUnited States60612
5GSK Investigational SiteChicagoIllinoisUnited States60637
6GSK Investigational SiteIndianapolisIndianaUnited States46202
7GSK Investigational SiteFairwayKansasUnited States66205
8GSK Investigational SiteNew OrleansLouisianaUnited States70121
9GSK Investigational SiteBaltimoreMarylandUnited States21201
10GSK Investigational SiteBostonMassachusettsUnited States02215
11GSK Investigational SiteRochesterMinnesotaUnited States55905
12GSK Investigational SiteNew YorkNew YorkUnited States10029
13GSK Investigational SiteNew YorkNew YorkUnited States10065
14GSK Investigational SiteCharlotteNorth CarolinaUnited States28204
15GSK Investigational SiteColumbusOhioUnited States43210
16GSK Investigational SitePhiladelphiaPennsylvaniaUnited States19104
17GSK Investigational SiteNashvilleTennesseeUnited States37232
18GSK Investigational SiteHoustonTexasUnited States77030
19GSK Investigational SiteSalt Lake CityUtahUnited States84112
20GSK Investigational SiteSeattleWashingtonUnited States98109
21GSK Investigational SiteMadisonWisconsinUnited States53792
22GSK Investigational SiteWoodvilleSouth AustraliaAustralia5011
23GSK Investigational SiteFitzroyVictoriaAustralia3065
24GSK Investigational SiteMelbourneVictoriaAustralia3004
25GSK Investigational SiteCalgaryAlbertaCanadaT2N 4N2
26GSK Investigational SiteWinnipegManitobaCanadaR3E 0V9
27GSK Investigational SiteTorontoOntarioCanadaM5G 2M9
28GSK Investigational SiteLille CedexFrance59037
29GSK Investigational SiteNantes cedex 1France44093
30GSK Investigational SiteParisFrance75010
31GSK Investigational SitePessacFrance33600
32GSK Investigational SitePierre-Bénite cedexFrance69495
33GSK Investigational SiteToulouse cedex 9France31059
34GSK Investigational SiteTuebingenBaden-WuerttembergGermany72076
35GSK Investigational SiteWuerzburgBayernGermany97080
36GSK Investigational SiteSchwerinMecklenburg-VorpommernGermany19049
37GSK Investigational SiteHannoverNiedersachsenGermany30625
38GSK Investigational SiteKoblenzRheinland-PfalzGermany56068
39GSK Investigational SiteDresdenSachsenGermany01307
40GSK Investigational SiteRionero In Vulture (Pz)BasilicataItaly85028
41GSK Investigational SiteParmaEmilia-RomagnaItaly43126
42GSK Investigational SiteAviano (PN)Friuli-Venezia-GiuliaItaly33081
43GSK Investigational SiteTorinoPiemonteItaly10126
44GSK Investigational SiteBadalonaSpain08916
45GSK Investigational SiteBarcelonaSpain08036
46GSK Investigational SiteGranadaSpain18014
47GSK Investigational SiteMadridSpain28041
48GSK Investigational SiteMurciaSpain30008
49GSK Investigational SitePamplonaSpain31008
50GSK Investigational SitePozuelo De Alarcón/MadridSpain28223
51GSK Investigational SiteSalamancaSpain37007
52GSK Investigational SiteValenciaSpain46017
53GSK Investigational SiteStoke-on-TrentStaffordshireUnited KingdomST4 6QG
54GSK Investigational SiteSuttonSurreyUnited KingdomSM2 5PT
55GSK Investigational SiteBirminghamUnited KingdomB9 5SS
56GSK Investigational SiteBournemouthUnited KingdomBH7 7DW
57GSK Investigational SiteHeadington, OxfordUnited KingdomOX3 7LE
58GSK Investigational SiteLondonUnited KingdomNW1 2BU
59GSK Investigational SiteNottinghamUnited KingdomNG5 1PB

Sponsors and Collaborators

  • GlaxoSmithKline

Investigators

  • Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

More Information

Publications

Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT03525678
Other Study ID Numbers:
  • 205678
  • 2017-004810-25
First Posted:
May 16, 2018
Last Update Posted:
Oct 4, 2021
Last Verified:
Sep 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by GlaxoSmithKline
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment DetailsThis was a Phase II, open-label, randomized, multicenter study to evaluate the efficacy and safety of belantamab mafodotin monotherapy at a dose of 2.5 milligram per kilogram (mg/kg) or 3.4 mg/kg, given intravenously (IV) in participants with relapsed/refractory multiple myeloma (RRMM).
Pre-assignment DetailA total of 293 participants were screened and 221 participants were enrolled and randomized in this study. The results presented are based on the interim analysis.
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Period Title: Overall Study
STARTED979925
Received Study Treatment959924
COMPLETED000
NOT COMPLETED979925

Baseline Characteristics

Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)Total
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.Total of all reporting groups
Overall Participants979925221
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
64.1
(10.01)
66.0
(9.09)
67.2
(10.78)
65.3
(10.01)
Sex: Female, Male (Count of Participants)
Female
46
47.4%
43
43.4%
11
44%
100
45.2%
Male
51
52.6%
56
56.6%
14
56%
121
54.8%
Race/Ethnicity, Customized (Count of Participants)
Black or African American
16
16.5%
11
11.1%
3
12%
30
13.6%
Asian - Central/South Asian Heritage
1
1%
0
0%
0
0%
1
0.5%
Asian - East Asian Heritage
1
1%
0
0%
0
0%
1
0.5%
Asian - South East Asian Heritage
0
0%
1
1%
1
4%
2
0.9%
White - Arabic/North African Heritage
4
4.1%
2
2%
0
0%
6
2.7%
White - White/Caucasian/European Heritage
72
74.2%
83
83.8%
21
84%
176
79.6%
Mixed Asian Race
0
0%
1
1%
0
0%
1
0.5%
Mixed White Race
0
0%
1
1%
0
0%
1
0.5%
Unknown
1
1%
0
0%
0
0%
1
0.5%
Missing
2
2.1%
0
0%
0
0%
2
0.9%

Outcome Measures

1. Primary Outcome
TitleOverall Response Rate (ORR) by Independent Review Committee (IRC) (Full Analysis Population)
DescriptionORR was determined according to the 2016 international myeloma working group (IMWG) response criteria by IRC. ORR was calculated as the percentage of participants with a confirmed partial response (PR) or better (that is [i.e.], PR, very good partial response [VGPR], complete response [CR] and stringent complete response [sCR]). Confidence intervals were based on the exact method.
Time FrameUp to 48 weeks

Outcome Measure Data

Analysis Population Description
Full Analysis Population comprised of all randomized participants (any participant who received a treatment randomization number was considered as randomized) whether or not randomized treatment was administered. This population was based on the treatment the participant was randomized to.
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants979925
Number (97.5% Confidence Interval) [Percentage of Participants]
31
32%
34
34.3%
48
192%
2. Primary Outcome
TitleOverall Response Rate by Independent Review Committee (Efficacy Population)
DescriptionORR was determined according to the 2016 IMWG response criteria by IRC. ORR was calculated as the percentage of participants with a confirmed PR or better (i.e., PR, VGPR, CR and sCR). Confidence intervals were based on the exact method. Efficacy Population comprised of first 130 intent-to-treat participants whether or not randomized treatment (frozen solution) was administered. Intent-to-treat Population comprised of all randomized participants whether or not randomized treatment was administered.
Time FrameUp to 48 weeks

Outcome Measure Data

Analysis Population Description
Efficacy Population. Data is not presented for 'GSK2857916 3.4 mg/kg (Lyophilized)' arm as it is not included in Efficacy Population.
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.
Measure Participants6466
Number (95% Confidence Interval) [Percentage of Participants]
30
30.9%
30
30.3%
3. Secondary Outcome
TitleOverall Response Rate by Investigator Assessment (IA) (Full Analysis Population)
DescriptionORR was determined by the investigator according to the 2016 IMWG response criteria. ORR was calculated as the percentage of participants with a confirmed PR or better (i.e., PR, VGPR, CR and sCR). Confidence intervals were based on the exact method.
Time FrameUp to 48 weeks

Outcome Measure Data

Analysis Population Description
Full Analysis Population
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants979925
Number (95% Confidence Interval) [Percentage of Participants]
30
30.9%
31
31.3%
52
208%
4. Secondary Outcome
TitleOverall Response Rate by Investigator Assessment (Efficacy Population)
DescriptionORR was determined by the investigator according to the 2016 IMWG response criteria. ORR was calculated as the percentage of participants with a confirmed PR or better (i.e., PR, VGPR, CR and sCR). Confidence intervals were based on the exact method.
Time FrameUp to 48 weeks

Outcome Measure Data

Analysis Population Description
Efficacy Population. Data is not presented for 'GSK2857916 3.4 mg/kg (Lyophilized)' arm as it is not included in Efficacy Population.
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.
Measure Participants6466
Number (95% Confidence Interval) [Percentage of Participants]
30
30.9%
26
26.3%
5. Secondary Outcome
TitleClinical Benefit Rate (CBR) by Investigator Assessment (Full Analysis Population)
DescriptionCBR was determined by the investigator according to the 2016 IMWG response criteria. CBR was calculated as the percentage of participants with a confirmed minimal response (MR) or better (i.e., MR, PR, VGPR, CR and sCR). Confidence intervals were based on the exact method.
Time FrameUp to 48 weeks

Outcome Measure Data

Analysis Population Description
Full Analysis Population
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants979925
Number (95% Confidence Interval) [Percentage of Participants]
34
35.1%
37
37.4%
56
224%
6. Secondary Outcome
TitleClinical Benefit Rate by Investigator Assessment (Efficacy Population)
DescriptionCBR was determined by the investigator according to the 2016 IMWG response criteria. CBR was calculated as the percentage of participants with a confirmed MR or better (i.e., MR, PR, VGPR, CR and sCR). Confidence intervals were based on the exact method.
Time FrameUp to 48 weeks

Outcome Measure Data

Analysis Population Description
Efficacy Population. Data is not presented for 'GSK2857916 3.4 mg/kg (Lyophilized)' arm as it is not included in Efficacy Population.
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.
Measure Participants6466
Number (95% Confidence Interval) [Percentage of Participants]
34
35.1%
33
33.3%
7. Secondary Outcome
TitleClinical Benefit Rate by Independent Review Committee (Full Analysis Population)
DescriptionCBR was determined according to the 2016 IMWG response criteria by IRC. CBR was calculated as the percentage of participants with a confirmed MR or better (i.e., MR, PR, VGPR, CR and sCR). Confidence intervals were based on the exact method.
Time FrameUp to 48 weeks

Outcome Measure Data

Analysis Population Description
Full Analysis Population
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants979925
Number (95% Confidence Interval) [Percentage of Participants]
34
35.1%
39
39.4%
52
208%
8. Secondary Outcome
TitleClinical Benefit Rate by Independent Review Committee (Efficacy Population)
DescriptionCBR was determined according to the 2016 IMWG response criteria by IRC. CBR was calculated as the percentage of participants with a confirmed MR or better (i.e., MR, PR, VGPR, CR and sCR). Confidence intervals were based on the exact method.
Time FrameUp to 48 weeks

Outcome Measure Data

Analysis Population Description
Efficacy Population. Data is not presented for 'GSK2857916 3.4 mg/kg (Lyophilized)' arm as it is not included in Efficacy Population.
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.
Measure Participants6466
Number (95% Confidence Interval) [Percentage of Participants]
33
34%
36
36.4%
9. Secondary Outcome
TitleDuration of Response (DoR) by Investigator Assessment (Full Analysis Population)
DescriptionDoR is defined as the time from first documented evidence of PR or better until the earliest date of documented disease progression (PD) per IMWG response criteria; or death due to PD among participants who achieved an overall response, i.e., confirmed PR or better. DOR based on responses assessed by investigator is presented. Median and inter-quartile range (first quartile and third quartile) of DOR are presented.
Time FrameUp to 48 weeks

Outcome Measure Data

Analysis Population Description
Full Analysis Population. Only those participants with data available at the specified data points were analyzed.
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants293113
Median (Inter-Quartile Range) [Months]
NA
NA
NA
10. Secondary Outcome
TitleDuration of Response by Investigator Assessment (Efficacy Population)
DescriptionDoR is defined as the time from first documented evidence of PR or better until the earliest date of documented PD per IMWG response criteria; or death due to PD among participants who achieved an overall response, i.e., confirmed PR or better. DOR based on responses assessed by investigator is presented. Median and inter-quartile range (first quartile and third quartile) of DOR are presented.
Time FrameUp to 48 weeks

Outcome Measure Data

Analysis Population Description
Efficacy Population. Data is not presented for 'GSK2857916 3.4 mg/kg (Lyophilized)' arm as it is not included in Efficacy Population. Only those participants with data available at the specified data points were analyzed.
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.
Measure Participants1917
Median (Inter-Quartile Range) [Months]
NA
NA
11. Secondary Outcome
TitleDuration of Response by Independent Review Committee (Full Analysis Population)
DescriptionDoR is defined as the time from first documented evidence of PR or better until the earliest date of documented PD per IMWG response criteria; or death due to PD among participants who achieved an overall response, i.e., confirmed PR or better. DOR based on responses assessed by IRC is presented. Median and inter-quartile range (first quartile and third quartile) of DOR are presented.
Time FrameUp to 48 weeks

Outcome Measure Data

Analysis Population Description
Full Analysis Population. Only those participants with data available at the specified data points were analyzed.
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants303412
Median (Inter-Quartile Range) [Months]
NA
NA
NA
12. Secondary Outcome
TitleDuration of Response by Independent Review Committee (Efficacy Population)
DescriptionDoR is defined as the time from first documented evidence of PR or better until the earliest date of documented PD per IMWG response criteria; or death due to PD among participants who achieved an overall response, i.e., confirmed PR or better. DOR based on responses assessed by IRC is presented. Median and inter-quartile range (first quartile and third quartile) of DOR are presented.
Time FrameUp to 48 weeks

Outcome Measure Data

Analysis Population Description
Efficacy Population. Data is not presented for 'GSK2857916 3.4 mg/kg (Lyophilized)' arm as it is not included in Efficacy Population. Only those participants with data available at the specified data points were analyzed.
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.
Measure Participants1920
Median (Inter-Quartile Range) [Months]
NA
NA
13. Secondary Outcome
TitleTime to Response by Investigator Assessment (Full Analysis Population)
DescriptionTime to response is defined as the time between the date of randomization and the first documented evidence of response (PR or better), among participants who achieve a response (i.e., confirmed PR or better). Time to response based on responses assessed by investigator is presented. Median and inter-quartile range (first quartile and third quartile) of time to response are presented.
Time FrameUp to 48 weeks

Outcome Measure Data

Analysis Population Description
Full Analysis Population. Only those participants with data available at the specified data points were analyzed.
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants293113
Median (Inter-Quartile Range) [Months]
1.4
1.5
0.9
14. Secondary Outcome
TitleTime to Response by Investigator Assessment (Efficacy Population)
DescriptionTime to response is defined as the time between the date of randomization and the first documented evidence of response (PR or better), among participants who achieve a response (i.e., confirmed PR or better). Time to response based on responses assessed by investigator is presented. Median and inter-quartile range (first quartile and third quartile) of time to response are presented.
Time FrameUp to 48 weeks

Outcome Measure Data

Analysis Population Description
Efficacy Population. Data is not presented for 'GSK2857916 3.4 mg/kg (Lyophilized)' arm as it is not included in Efficacy Population. Only those participants with data available at the specified data points were analyzed.
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.
Measure Participants1917
Median (Inter-Quartile Range) [Months]
1.4
1.5
15. Secondary Outcome
TitleTime to Response by Independent Review Committee (Full Analysis Population)
DescriptionTime to response is defined as the time between the date of randomization and the first documented evidence of response (PR or better), among participants who achieve a response (i.e., confirmed PR or better). Time to response based on responses assessed by IRC is presented. Median and inter-quartile range (first quartile and third quartile) of time to response are presented.
Time FrameUp to 48 weeks

Outcome Measure Data

Analysis Population Description
Full Analysis Population. Only those participants with data available at the specified data points were analyzed.
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants303412
Median (Inter-Quartile Range) [Months]
1.4
1.4
0.9
16. Secondary Outcome
TitleTime to Response by Independent Review Committee (Efficacy Population)
DescriptionTime to response is defined as the time between the date of randomization and the first documented evidence of response (PR or better), among participants who achieve a response (i.e., confirmed PR or better). Time to response based on responses assessed by IRC is presented. Median and inter-quartile range (first quartile and third quartile) of time to response are presented.
Time FrameUp to 48 weeks

Outcome Measure Data

Analysis Population Description
Efficacy Population. Data is not presented for 'GSK2857916 3.4 mg/kg (Lyophilized)' arm as it is not included in Efficacy Population. Only those participants with data available at the specified data points were analyzed.
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.
Measure Participants1920
Median (Inter-Quartile Range) [Months]
1.5
1.4
17. Secondary Outcome
TitleProgression Free Survival by Investigator Assessment
DescriptionProgression free survival is defined as the time from randomization until the earliest date of documented PD per IMWG, or death due to any cause. Progression free survival based on responses assessed by investigator is presented. Median and inter-quartile range (first quartile and third quartile) of progression free survival are presented.
Time FrameUp to 48 weeks

Outcome Measure Data

Analysis Population Description
Full Analysis Population
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants979925
Median (Inter-Quartile Range) [Months]
2.2
3.8
4.3
18. Secondary Outcome
TitleProgression Free Survival by Independent Review Committee
DescriptionProgression free survival is defined as the time from randomization until the earliest date of documented PD per IMWG, or death due to any cause. Progression free survival based on responses assessed by IRC is presented. Median and inter-quartile range (first quartile and third quartile) of progression free survival are presented.
Time FrameUp to 48 weeks

Outcome Measure Data

Analysis Population Description
Full Analysis Population
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants979925
Median (Inter-Quartile Range) [Months]
2.9
4.9
NA
19. Secondary Outcome
TitleTime to Progression by Investigator Assessment
DescriptionTime to progression is defined as the time from randomization until the earliest date of documented PD per IMWG, or death due to PD. Time to Progression based on responses assessed by investigator is presented. Median and inter-quartile range (first quartile and third quartile) of time to progression are presented.
Time FrameUp to 48 weeks

Outcome Measure Data

Analysis Population Description
Full Analysis Population
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants979925
Median (Inter-Quartile Range) [Months]
2.3
4.2
4.3
20. Secondary Outcome
TitleTime to Progression by Independent Review Committee
DescriptionTime to progression is defined as the time from randomization until the earliest date of documented PD per IMWG, or death due to PD. Time to Progression based on responses assessed by IRC is presented. Median and inter-quartile range (first quartile and third quartile) of time to progression are presented.
Time FrameUp to 48 weeks

Outcome Measure Data

Analysis Population Description
Full Analysis Population
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants979925
Median (Inter-Quartile Range) [Months]
3.0
5.8
NA
21. Secondary Outcome
TitleOverall Survival
DescriptionOverall survival is defined as the time from randomization until death due to any cause. Overall survival was analyzed using the Kaplan-Meier method by dose level. Median and inter-quartile range (first quartile and third quartile) of overall survival are presented.
Time FrameUp to 48 weeks

Outcome Measure Data

Analysis Population Description
Full Analysis Population
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants979925
Median (Inter-Quartile Range) [Months]
9.9
9.7
NA
22. Secondary Outcome
TitleNumber of Participants With Change From Baseline in Hematology Parameters With Respect to the Normal Range
DescriptionFollowing parameters were assessed:basophils(Baso),eosinophils(Eosino),hematocrit(Hct),mean corpuscular hemoglobin(MCH),MCH concentration(MCHC),MC volume(MCV),monocyte(Mono),erythrocytes(Erythro),reticulocytes(Reticu).Baseline is latest pre-dose assessment(Day1)with a non-missing value, including unscheduled visits.Data was categorized as decrease to low(value below lower limit of normal range[LNR]),increase to high(value above upper LNR),change to normal/no change(NC).If values were unchanged(eg.high to high) or whose value became normal,were recorded in change to normal/NC category.Participants were counted twice if participant had both decreased to low/increased to high during post-Baseline(PB).Data for worst case PB is presented.Full Safety Population(FSP) comprised of all participants who received at least 1dose of study drug(frozen liquid or lyophilized powder). 3 out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population.
Time FrameBaseline (Day 1) and Up to 48 weeks

Outcome Measure Data

Analysis Population Description
Full Safety Population. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants959924
Baso, decrease to low, n=94,96,23
2
2.1%
6
6.1%
0
0%
Baso, change to normal or NC, n=94,96,23
89
91.8%
86
86.9%
22
88%
Baso, increase to high, n=94,96,23
3
3.1%
4
4%
1
4%
Eosino, decrease to low, n=95,97,23
12
12.4%
11
11.1%
0
0%
Eosino, change to normal or NC, n=95,97,23
78
80.4%
82
82.8%
18
72%
Eosino, increase to high, n=95,97,23
5
5.2%
6
6.1%
5
20%
Hct, decrease to low, n=95,97,24
9
9.3%
3
3%
1
4%
Hct, change to normal or NC, n=95,97,24
86
88.7%
94
94.9%
23
92%
Hct, increase to high, n=95,97,24
1
1%
0
0%
0
0%
MCH, decrease to low, n=95,95,21
10
10.3%
16
16.2%
2
8%
MCH, change to normal or NC, n=95,95,21
83
85.6%
71
71.7%
18
72%
MCH, increase to high, n=95,95,21
2
2.1%
9
9.1%
1
4%
MCHC, decrease to low, n=94,96,21
19
19.6%
25
25.3%
4
16%
MCHC, change to normal or NC, n=94,96,21
73
75.3%
71
71.7%
17
68%
MCHC, increase to high, n=94,96,21
2
2.1%
0
0%
0
0%
MCV, decrease to low, n=95,97,24
9
9.3%
12
12.1%
1
4%
MCV, change to normal or NC, n=95,97,24
80
82.5%
77
77.8%
21
84%
MCV, increase to high, n=95,97,24
6
6.2%
8
8.1%
2
8%
Mono, decrease to low, n=95,97,24
6
6.2%
8
8.1%
0
0%
Mono, change to normal or NC, n=95,97,24
63
64.9%
53
53.5%
14
56%
Mono, increase to high, n=95,97,24
27
27.8%
42
42.4%
10
40%
Erythro, decrease to low, n=95,97,24
3
3.1%
1
1%
0
0%
Erythro, change to normal or NC, n=95,97,24
92
94.8%
95
96%
23
92%
Erythro, increase to high, n=95,97,24
1
1%
1
1%
1
4%
Reticu, decrease to low, n=68,62,18
7
7.2%
11
11.1%
5
20%
Reticu, change to normal or NC, n=68,62,18
50
51.5%
37
37.4%
6
24%
Reticu, increase to high, n=68,62,18
12
12.4%
17
17.2%
8
32%
23. Secondary Outcome
TitleNumber of Participants With Grade Change From Baseline in Hematology Parameters
DescriptionBlood samples were collected for the analysis of following hematology parameters: hemoglobin (Hb), lymphocyte count (Lymph), neutrophil count (Neutro), platelet count (PC), and leukocyte count (leuko). The laboratory parameters were graded according to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as latest pre-dose assessment (Day 1) 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. Only those participants with increase to grade 3 and increase to grade 4 have been presented.
Time FrameBaseline (Day 1) and Up to 48 weeks

Outcome Measure Data

Analysis Population Description
Full Safety Population. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population.
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants959924
Hb, Hb increased, increase to Grade 3
0
0%
0
0%
0
0%
Hb, Hb increased, increase to Grade 4
0
0%
0
0%
0
0%
Hb, Anemia, increase to Grade 3
17
17.5%
28
28.3%
4
16%
Hb, Anemia, increase to Grade 4
0
0%
0
0%
0
0%
Lymph, Lymph count increased, increase to Grade 3
0
0%
0
0%
0
0%
Lymph, Lymph count increased, increase to Grade 4
0
0%
0
0%
0
0%
Lymph, Lymph count decreased, increase to Grade 3
16
16.5%
24
24.2%
6
24%
Lymph, Lymph count decreased, increase to Grade 4
5
5.2%
5
5.1%
0
0%
Neutro, increase to Grade 3
4
4.1%
11
11.1%
2
8%
Neutro, increase to Grade 4
5
5.2%
2
2%
1
4%
PC, increase to Grade 3
8
8.2%
12
12.1%
1
4%
PC, increase to Grade 4
12
12.4%
23
23.2%
2
8%
Leuko, Leukocytosis, increase to Grade 3
0
0%
0
0%
0
0%
Leuko, Leukocytosis, increase to Grade 4
0
0%
0
0%
0
0%
Leuko, Leuko decreased, increase to Grade 3
5
5.2%
9
9.1%
1
4%
Leuko, Leuko decreased, increase to Grade 4
3
3.1%
2
2%
0
0%
24. Secondary Outcome
TitleNumber of Participants With Change From Baseline in Clinical Chemistry Parameters With Respect to the Normal Range
DescriptionBlood samples were collected for analysis of clinical chemistry parameters: bicarbonate, direct bilirubin(D.Bil), calcium, chloride, lactate dehydrogenase(LDH), total protein, urea or blood urea nitrogen(BUN),estimated glomerular filtration rate (eGFR).Baseline is latest pre-dose assessment(Day 1) with a non-missing value, including unscheduled visits. Number of participants with worst case clinical chemistry change from Baseline with respect to normal range are presented. Data was categorized as decrease to low (value below the lower LNR), increase to high (value above the upper LNR) and change to normal or NC. If values were unchanged (example: high to high), or whose value became normal, were recorded in the change to normal or NC category. Participants were counted twice if the participant had both decreased to low and increased to high during post Baseline. 3 out of 221participants did not receive any study treatment, were excluded from FSP.
Time FrameBaseline (Day 1) and Up to 48 weeks

Outcome Measure Data

Analysis Population Description
Full Safety Population. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants959924
Bicarbonate, decrease to low, n=90,93,24
8
8.2%
19
19.2%
3
12%
Bicarbonate, change to normal or NC, n=90,93,24
72
74.2%
63
63.6%
18
72%
Bicarbonate, increase to high, n=90,93,24
10
10.3%
14
14.1%
3
12%
D.Bil, decrease to low, n=69,70,21
0
0%
1
1%
0
0%
D.Bil, change to normal or NC, n=69,70,21
64
66%
63
63.6%
21
84%
D.Bil, increase to high, n=69,70,21
5
5.2%
6
6.1%
0
0%
Calcium, decrease to low, n=95,98,24
24
24.7%
26
26.3%
7
28%
Calcium, change to normal or NC, n=95,98,24
55
56.7%
52
52.5%
9
36%
Calcium, increase to high, n=95,98,24
25
25.8%
23
23.2%
8
32%
Chloride, decrease to low, n=94,97,24
15
15.5%
12
12.1%
2
8%
Chloride, change to normal or NC, n=94,97,24
66
68%
65
65.7%
20
80%
Chloride, increase to high, n=94,97,24
13
13.4%
23
23.2%
2
8%
LDH, decrease to low, n=92,98,23
1
1%
1
1%
0
0%
LDH, change to normal or NC, n=92,98,23
47
48.5%
54
54.5%
12
48%
LDH, increase to high, n=92,98,23
44
45.4%
44
44.4%
11
44%
Protein, decrease to low, n=94,98,24
29
29.9%
27
27.3%
8
32%
Protein, change to normal or NC, n=94,98,24
51
52.6%
64
64.6%
14
56%
Protein, increase to high, n=94,98,24
17
17.5%
7
7.1%
2
8%
BUN, decrease to low, n=90,93,24
10
10.3%
13
13.1%
0
0%
BUN, change to normal or NC, n=90,93,24
69
71.1%
60
60.6%
18
72%
BUN, increase to high, n=90,93,24
12
12.4%
22
22.2%
6
24%
eGFR, decrease to low, n=51,67,19
9
9.3%
10
10.1%
5
20%
eGFR, change to normal or NC, n=51,67,19
42
43.3%
56
56.6%
14
56%
eGFR, increase to high, n=51,67,19
0
0%
1
1%
1
4%
25. Secondary Outcome
TitleNumber of Participants With Grade Change From Baseline in Clinical Chemistry Parameters
DescriptionBlood samples were collected for analysis of clinical chemistry parameters: glucose(Gl), albumin, alkaline phosphatase (ALP), alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bilirubin(T.Bil), creatinine kinase (CK), creatinine, gamma glutamyl transferase (GGT), potassium (Pot), magnesium (Mg), sodium (Sod), phosphate (Ph) and urate. Values (Hyper and hypo) for Gl, Pot, Mg and Sod is presented. Laboratory parameters were graded according to NCI-CTCAE version 4.03. Grade1: mild; Grade2: moderate; Grade3: severe or medically significant; Grade4: life-threatening consequences. Baseline is latest pre-dose assessment(Day 1) 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 PB is presented. Only those participants with increase to grade3 and increase to grade4 have been presented. 3 out of 221participants did not receive any study treatment, were excluded from FSP.
Time FrameBaseline (Day 1) and Up to 48 weeks

Outcome Measure Data

Analysis Population Description
Full Safety Population. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants959924
Gl, Hyper, increase to Grade 3, n=94,95,24
3
3.1%
4
4%
0
0%
Gl, Hyper, increase to Grade 4, n=94,95,24
0
0%
0
0%
0
0%
Gl, Hypo, increase to Grade 3, n=94,95,24
0
0%
0
0%
0
0%
Gl, Hypo, increase to Grade 4, n=94,95,24
0
0%
0
0%
0
0%
Albumin, increase to Grade 3, n=94,98,24
4
4.1%
7
7.1%
1
4%
Albumin, increase to Grade 4, n=94,98,24
0
0%
0
0%
0
0%
ALP, increase to Grade 3, n=93,97,24
1
1%
0
0%
0
0%
ALP, increase to Grade 4, n=93,97,24
0
0%
0
0%
0
0%
ALT, increase to Grade 3, n=93,97,24
0
0%
0
0%
0
0%
ALT, increase to Grade 4, n=93,97,24
0
0%
0
0%
0
0%
AST, increase to Grade 3, n=93,96,24
2
2.1%
5
5.1%
0
0%
AST, increase to Grade 4, n=93,96,24
0
0%
0
0%
0
0%
T.Bil, increase to Grade 3, n=92,97,23
0
0%
0
0%
0
0%
T.Bil, increase to Grade 4, n=92,97,23
0
0%
0
0%
0
0%
CK, increase to Grade 3, n= 87,91,24
0
0%
0
0%
1
4%
CK, increase to Grade 4, n= 87,91,24
1
1%
0
0%
0
0%
Creatinine, increase to Grade 3, n= 95,97,24
4
4.1%
3
3%
0
0%
Creatinine, increase to Grade 4, n= 95,97,24
1
1%
0
0%
0
0%
GGT, increase to Grade 3, n= 91,95,24
5
5.2%
9
9.1%
0
0%
GGT, increase to Grade 4, n= 91,95,24
0
0%
1
1%
0
0%
Pot, Hyper,increase to Grade 3, n= 95,97,24
0
0%
1
1%
0
0%
Pot, Hyper,increase to Grade 4, n= 95,97,24
0
0%
0
0%
0
0%
Pot, Hypo, increase to Grade 3, n= 95,97,24
0
0%
2
2%
1
4%
Pot, Hypo, increase to Grade 4, n= 95,97,24
2
2.1%
0
0%
0
0%
Mg, Hyper, increase to Grade 3, n= 91,96,24
3
3.1%
0
0%
0
0%
Mg, Hyper, increase to Grade 4, n= 91,96,24
0
0%
0
0%
0
0%
Mg, Hypo, increase to Grade 3, n= 91,96,24
0
0%
0
0%
0
0%
Mg, Hypo, increase to Grade 4, n= 91,96,24
0
0%
0
0%
0
0%
Phosphate, increase to Grade 3, n= 90,93,24
4
4.1%
6
6.1%
1
4%
Phosphate, increase to Grade 4, n= 90,93,24
0
0%
0
0%
0
0%
Sod, Hyper, increase to Grade 3, n= 95,97,24
0
0%
0
0%
0
0%
Sod, Hyper, increase to Grade 4, n= 95,97,24
0
0%
0
0%
0
0%
Sod, Hypo, increase to Grade 3, n= 95,97,24
2
2.1%
6
6.1%
1
4%
Sod, Hypo, increase to Grade 4, n= 95,97,24
0
0%
0
0%
0
0%
Urate, increase to Grade 3, n= 93,96,24
0
0%
0
0%
0
0%
Urate, increase to Grade 4, n= 93,96,24
3
3.1%
4
4%
0
0%
26. Secondary Outcome
TitleNumber of Participants With Abnormal Findings During Physical Examination
DescriptionPhysical examination included assessment of the head, eyes, ears, nose, throat, skin, thyroid, lungs, cardiovascular, abdomen (liver and spleen), lymph nodes, and extremities. This analysis was planned, but data was not collected and captured in the database.
Time FrameUp to 48 weeks

Outcome Measure Data

Analysis Population Description
Full Safety Population. This analysis was planned, but data was not collected and captured in the database.
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants000
27. Secondary Outcome
TitleNumber of Participants With Change From Baseline in Pulse Rate
DescriptionBaseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. Number of participants with worst case change from Baseline in pulse rate is presented. Data is categorized as: pulse rate 'decrease to <60 beats per minute [bpm]', 'increase to >100 bpm' and 'change to normal or no change'. If values were unchanged (example: increase to >100 bpm to increase to >100 bpm), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to <60 bpm' and 'increased to >100 bpm' during post Baseline. Data for worst-case post Baseline is presented.
Time FrameBaseline (Day 1) and Up to 48 weeks

Outcome Measure Data

Analysis Population Description
Full Safety Population. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population.
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants959924
Decrease to <60
12
12.4%
15
15.2%
5
20%
Change to normal or no change
59
60.8%
58
58.6%
17
68%
Increase to >100
25
25.8%
27
27.3%
2
8%
28. Secondary Outcome
TitleNumber of Participants With Change From Baseline in Body Temperature
DescriptionBaseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. Number of participants with worst case change from Baseline in body temperature are presented. Data is categorized as: body temperature 'decrease to <=35 degrees celsius', 'increase to >=38 degrees celsius' and 'change to normal or no change'. If values were unchanged (example: increase to >=38 to increase to >=38 degrees celsius), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to <=35' and 'increased to >=38 degrees celsius' during post Baseline. Data for worst-case post Baseline is presented.
Time FrameBaseline (Day 1) and Up to 48 weeks

Outcome Measure Data

Analysis Population Description
Full Safety Population. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population.
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants959924
Decrease to <=35
1
1%
2
2%
0
0%
Change to normal or no change
86
88.7%
86
86.9%
21
84%
Increase to >=38
8
8.2%
10
10.1%
3
12%
29. Secondary Outcome
TitleNumber of Participants With Grade Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DescriptionSBP and DBP were graded using NCI CTCAE version 4.03. For SBP: Grade 0: <120 millimeter mercury (mmHg); Grade 1: 120-139 mmHg; Grade 2: 140-159 mmHg; Grade 3: >=160 mmHg. For DBP: Grade 0: <80 mmHg; Grade 1: 80-89 mmHg; Grade 2: 90-99 mmHg; Grade 3: >=100 mmHg. Baseline was defined as the latest pre-dose assessment (Day 1) 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. Only those participants with increase to grade 2 and increase to grade 3 have been presented.
Time FrameBaseline (Day 1) and Up to 48 weeks

Outcome Measure Data

Analysis Population Description
Full Safety Population. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population.
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants959924
SBP, increase to Grade 2
29
29.9%
42
42.4%
1
4%
SBP, increase to Grade 3
13
13.4%
19
19.2%
6
24%
DBP, increase to Grade 2
15
15.5%
14
14.1%
0
0%
DBP, increase to Grade 3
9
9.3%
7
7.1%
1
4%
30. Secondary Outcome
TitleNumber of Participants With Serious Adverse Events (SAEs), Common (>=5%) Non-serious Adverse Events and Adverse Events of Special Interest (AESI)
DescriptionAn adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that; results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician, is associated with liver injury and impaired liver function. Number of participants who had SAEs and common (>=5%) non-SAEs are presented. Number of participants with AESI (keratopathy, dry eye events, blurred vision, thrombocytopenia, infusion-related reactions, corneal events and neutropenia) are also presented.
Time FrameUp to 48 weeks

Outcome Measure Data

Analysis Population Description
Full Safety Population. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population.
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants959924
Common non-SAE
93
95.9%
96
97%
24
96%
SAE
38
39.2%
47
47.5%
15
60%
Keratopathy
67
69.1%
74
74.7%
22
88%
Dry eye events
13
13.4%
23
23.2%
6
24%
Blurred vision
21
21.6%
30
30.3%
7
28%
Thrombocytopenia
33
34%
58
58.6%
10
40%
Infusion-related reactions
20
20.6%
16
16.2%
3
12%
Corneal events
67
69.1%
76
76.8%
22
88%
Neutropenia
13
13.4%
27
27.3%
2
8%
31. Secondary Outcome
TitleNumber of Participants With Change From Baseline in Best Corrected Visual Acuity (BCVA) Test Scores
DescriptionBaseline was defined as latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. BCVA score was assessed individually for each eye. BCVA test scores were categorized as no change/improved vision, possible worsened vision and definite worsened vision. No change/improved vision was defined as a change from Baseline <0.12 Logarithm of the Minimum Angle of Resolution (logMAR) score; a possible worsened vision was defined as a change from Baseline >=0.12 to <0.3 logMAR score; a definite worsened vision was defined as a change from Baseline >=0.3 logMAR score. Data for worst-case change from Baseline is presented. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population.
Time FrameBaseline (Day 1) and Up to 48 weeks

Outcome Measure Data

Analysis Population Description
Full Safety Population. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants959924
Left eye, no change/improved vision, n=88,94,24
38
39.2%
46
46.5%
6
24%
Left eye, possible worsened vision, n=88,94,24
12
12.4%
16
16.2%
3
12%
Left eye, definite worsened vision, n=88,94,24
38
39.2%
32
32.3%
15
60%
Right eye, no change/improved vision, n=87,93,23
34
35.1%
39
39.4%
5
20%
Right eye, possible worsened vision, n=87,93,23
24
24.7%
18
18.2%
8
32%
Right eye, definite worsened vision, n=87,93,23
29
29.9%
36
36.4%
10
40%
32. Secondary Outcome
TitleNumber of Participants With Intraocular Pressure (IOP) >=22 mmHg Anytime Post-Baseline
DescriptionBaseline was defined as latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. IOP was assessed individually for each eye. Number of participants with IOP >=22 mmHg anytime post-Baseline are presented. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population.
Time FrameUp to 48 weeks

Outcome Measure Data

Analysis Population Description
Full Safety Population. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants959924
Right eye, n=88,93,23
14
14.4%
13
13.1%
8
32%
Left eye, n=88,92,24
12
12.4%
12
12.1%
7
28%
33. Secondary Outcome
TitleNumber of Participants With Shift in Pupillary Examination Findings From Normal (Baseline) to Abnormal (Worst Post-Baseline)
DescriptionBaseline was defined as latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. Number of participants with shift in pupillary examination findings from normal (Baseline) to abnormal (worst post-Baseline) are presented.
Time FrameBaseline and Up to 48 weeks

Outcome Measure Data

Analysis Population Description
Full Safety Population. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population. Only those participants with data available at the specified data points were analyzed.
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants919023
Count of Participants [Participants]
4
4.1%
9
9.1%
1
4%
34. Secondary Outcome
TitleNumber of Participants With Shift in Extraocular Muscle Movement From Yes (Baseline) to no (Worst Post-Baseline)
DescriptionBaseline was defined as latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. Extraocular muscle movement was assessed individually for each eye. Number of participants with shift in extraocular muscle movement from yes (Baseline) to no (worst post-Baseline) are presented. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population.
Time FrameBaseline and Up to 48 weeks

Outcome Measure Data

Analysis Population Description
Full Safety Population. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants959924
Right eye,n=95,93,23
0
0%
4
4%
0
0%
Left eye,n=93,92,22
0
0%
2
2%
0
0%
35. Secondary Outcome
TitleNumber of Participants With Shift in Corneal Epithelium Findings From Normal (Baseline) to Abnormal (Worst Post-Baseline) for Corneal Epithelium (CE) and Corneal Stroma (CS)
DescriptionBaseline was defined as latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. Corneal epithelium findings for CE and CS were assessed individually for each eye. Number of participants with shift in corneal epithelium findings from normal (Baseline) to abnormal (worst post-Baseline) for CE and CS are presented. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population.
Time FrameBaseline and Up to 48 weeks

Outcome Measure Data

Analysis Population Description
Full Safety Population. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants959924
CE, Right eye, n=53,54,17
39
40.2%
40
40.4%
15
60%
CE, Left eye,n=55,55,15
39
40.2%
44
44.4%
13
52%
CS, Right eye,n=92,94,24
5
5.2%
4
4%
1
4%
CS, Left eye,n=92,89,23
6
6.2%
3
3%
2
8%
36. Secondary Outcome
TitleNumber of Participants With Shift in Corneal Epithelium Findings From no (Baseline) to Yes (Worst Post-Baseline)
DescriptionBaseline was defined as latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. Corneal epithelium findings like active edema, active opacity, corneal neovascularization (CN), corneal ulcer, epithelial microcystic edema (EME) and subepithelial were performed using a slit lamp. Number of participants with shift in corneal epithelium findings from no (Baseline) to yes (worst post-Baseline) are presented. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population.
Time FrameBaseline and Up to 48 weeks

Outcome Measure Data

Analysis Population Description
Full Safety Population. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants959924
Active edema, Right eye, n=94,99,24
3
3.1%
3
3%
1
4%
Active edema, Left eye,n=95,99,24
4
4.1%
2
2%
1
4%
Active opacity, Right eye,n=93,97,24
2
2.1%
2
2%
1
4%
Active opacity, Left eye,n=94,95,24
3
3.1%
2
2%
1
4%
CN, Right eye,n=93,99,24
1
1%
2
2%
0
0%
CN, Left eye,n=93,99,23
0
0%
1
1%
0
0%
Corneal ulcer, Right eye,n=61,60,22
0
0%
0
0%
0
0%
Corneal ulcer, Left eye,n=63,61,20
0
0%
1
1%
0
0%
EME, Right eye,n=95,99,24
13
13.4%
19
19.2%
7
28%
EME, Left eye,n=95,99,23
15
15.5%
21
21.2%
7
28%
Subepithelial haze, Right eye,n=95,98,24
14
14.4%
26
26.3%
5
20%
Subepithelial haze, Left eye,n=95,97,23
14
14.4%
25
25.3%
5
20%
37. Secondary Outcome
TitleNumber of Participants With Shift in Tear Break-up Time From >10 Seconds (Baseline) to <=5 Seconds (Worst Post-Baseline)
DescriptionBaseline was defined as latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. Number of participants with shift in tear break-up time from >10 seconds (Baseline) to <=5 seconds (worst post-Baseline) are presented. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population.
Time FrameBaseline and Up to 48 weeks

Outcome Measure Data

Analysis Population Description
Full Safety Population. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants959924
Left eye,n=34,30,2
12
12.4%
8
8.1%
0
0%
Right eye,n=30,31,2
11
11.3%
10
10.1%
0
0%
38. Secondary Outcome
TitleArea Under the Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC[0-infinity]) of GSK2857916 Following IV Dose in Participants With RRMM
DescriptionBlood samples were collected at designated timepoints. Pharmacokinetic (PK) parameters of GSK2857916 were calculated using non-compartmental methods. Full Pharmacokinetic (PK) Population comprised of all participants in the Full Safety Population who had atleast 1 non-missing PK assessment.
Time FrameCycle 1 and Cycle 3: Pre-dose, end of infusion (EOI), 2 hours and 24 hours post start of infusion (SOI) on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)

Outcome Measure Data

Analysis Population Description
Full PK Population. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants959924
Cycle 1,n=26,18,18
5644
(39.6)
6495
(54.3)
6962
(51.4)
Cycle 3, n=19,21,9
7848
(42.7)
9199
(45.1)
9694
(49.9)
39. Secondary Outcome
TitleArea Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK2857916 Following IV Dose in Participants With RRMM
DescriptionBlood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods.
Time FrameCycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)

Outcome Measure Data

Analysis Population Description
Full PK Population. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants959924
Cycle 1, n=30,20,22
4666
(45.7)
5678
(40.1)
5946
(37.2)
Cycle 3, n=26,24,11
6399
(31.6)
6941
(34.2)
7593
(34.5)
40. Secondary Outcome
TitleArea Under the Concentration-time Curve From Zero to Time of Last Quantifiable Concentration (AUC[0-tlast]) of GSK2857916 Following IV Dose in Participants With RRMM
DescriptionBlood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods.
Time FrameCycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)

Outcome Measure Data

Analysis Population Description
Full PK Population. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants959924
Cycle 1, n=32,21,22
4607
(54.4)
5567
(51.0)
6293
(45.7)
Cycle 3, n=28,28,11
6033
(44.7)
6084
(73.8)
8388
(46.1)
41. Secondary Outcome
TitleMaximum Observed Concentration (Cmax) of GSK2857916 Following IV Dose in Participants With RRMM
DescriptionBlood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods.
Time FrameCycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)

Outcome Measure Data

Analysis Population Description
Full PK Population. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants959924
Cycle 1, n=32,21,22
42.51
(26.3)
52.03
(19.8)
51.32
(18.3)
Cycle 3, n=29,28,11
42.35
(25.6)
45.5
(25.3)
48.06
(17.1)
42. Secondary Outcome
TitleTime to Reach Maximum Observed Concentration (Tmax) of GSK2857916 Following IV Dose in Participants With RRMM
DescriptionBlood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods.
Time FrameCycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)

Outcome Measure Data

Analysis Population Description
Full PK Population. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants959924
Cycle 1, n=32,21,22
0.780
0.700
0.750
Cycle 3, n=29,28,11
0.580
0.715
0.870
43. Secondary Outcome
TitleTerminal Half-life (t1/2) of GSK2857916 Following IV Dose in Participants With RRMM
DescriptionBlood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods.
Time FrameCycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)

Outcome Measure Data

Analysis Population Description
Full PK Population. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants959924
Cycle 1, n=29,19,22
164.4
(46.2)
165.8
(55.0)
196.2
(40.9)
Cycle 3, n=26,23,11
193.7
(48.4)
214.4
(45.9)
279.5
(40.3)
44. Secondary Outcome
TitleAUC(0-infinity) of GSK2857916 Total Antibody Following IV Dose in Participants With RRMM
DescriptionBlood samples were collected at designated timepoints. PK parameters of GSK2857916 total antibody were calculated using non-compartmental methods.
Time FrameCycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)

Outcome Measure Data

Analysis Population Description
Full PK Population. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants959924
Cycle 1, n=16,10,9
10268
(65.8)
10209
(64.9)
10170
(75.0)
Cycle 3, n=10,11,3
20526
(45.1)
18637
(69.4)
22782
(161.1)
45. Secondary Outcome
TitleAUC(0-tau) of GSK2857916 Total Antibody Following IV Dose in Participants With RRMM
DescriptionBlood samples were collected at designated timepoints. PK parameters of GSK2857916 total antibody were calculated using non-compartmental methods.
Time FrameCycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)

Outcome Measure Data

Analysis Population Description
Full PK Population. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants959924
Cycle 1, n=29,18,19
7305
(41.9)
9566
(42.2)
9029
(40.2)
Cycle 3, n=23,24,11
11243
(34.6)
11646
(38.0)
15311
(43.9)
46. Secondary Outcome
TitleAUC(0-tlast) of GSK2857916 Total Antibody Following IV Dose in Participants With RRMM
DescriptionBlood samples were collected at designated timepoints. PK parameters of GSK2857916 total antibody were calculated using non-compartmental methods.
Time FrameCycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)

Outcome Measure Data

Analysis Population Description
Full PK Population. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants959924
Cycle 1, n=30,19,20
7417
(58.5)
9628
(52.8)
9017
(55.4)
Cycle 3, n=27,26,11
10725
(59.4)
11295
(80.0)
17715
(61.0)
47. Secondary Outcome
TitleCmax of GSK2857916 Total Antibody Following IV Dose in Participants With RRMM
DescriptionBlood samples were collected at designated timepoints. PK parameters of GSK2857916 total antibody were calculated using non-compartmental methods.
Time FrameCycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)

Outcome Measure Data

Analysis Population Description
Full PK Population. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants959924
Cycle 1, n=30,19,20
48.94
(30.0)
61.06
(26.9)
60.08
(18.3)
Cycle 3, n=29,28,11
49.34
(32.9)
55.60
(26.5)
65.07
(17.4)
48. Secondary Outcome
TitleTmax of GSK2857916 Total Antibody Following IV Dose in Participants With RRMM
DescriptionBlood samples were collected at designated timepoints. PK parameters of GSK2857916 total antibody were calculated using non-compartmental methods.
Time FrameCycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)

Outcome Measure Data

Analysis Population Description
Full PK Population. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants959924
Cycle 1, n=30,19,20
1.750
1.870
0.650
Cycle 3, n=29,28,11
0.830
1.150
1.750
49. Secondary Outcome
Titlet1/2 of GSK2857916 Total Antibody Following IV Dose in Participants With RRMM
DescriptionBlood samples were collected at designated timepoints. PK parameters of GSK2857916 total antibody were calculated using non-compartmental methods.
Time FrameCycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)

Outcome Measure Data

Analysis Population Description
Full PK Population. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants959924
Cycle 1, n=29,17,19
241.8
(49.3)
250.8
(70.3)
299.8
(61.0)
Cycle 3, n=23,23,11
352.4
(52.6)
372.0
(49.6)
557.3
(91.7)
50. Secondary Outcome
TitleAUC(0-infinity) of Cysteine-maleimidocaproyl Monomethyl Auristatin F (Cys-mcMMAF) Following IV Dose of GSK2857916 in Participants With RRMM
DescriptionBlood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods.
Time FrameCycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)

Outcome Measure Data

Analysis Population Description
Full PK Population. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants959924
Cycle 1, n=27,20,19
NA
(NA)
NA
(NA)
NA
(NA)
Cycle 3, n=26,29,11
NA
(NA)
NA
(NA)
NA
(NA)
51. Secondary Outcome
TitleAUC(0-tau) of Cys-mcMMAF Following IV Dose of GSK2857916 in Participants With RRMM
DescriptionBlood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods.
Time FrameCycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)

Outcome Measure Data

Analysis Population Description
Full PK Population. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants959924
Cycle 1, n=27,20,19
NA
(NA)
NA
(NA)
NA
(NA)
Cycle 3, n=26,29,11
NA
(NA)
NA
(NA)
NA
(NA)
52. Secondary Outcome
TitleAUC(0-tlast) of Cysteine-maleimidocaproyl Monomethyl Auristatin F (Cys-mcMMAF) Following IV Dose of GSK2857916 in Participants With RRMM
DescriptionBlood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods.
Time FrameCycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)

Outcome Measure Data

Analysis Population Description
Full PK Population. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants959924
Cycle 1, n=27,20,19
79.26
(61.0)
113.57
(58.3)
100.35
(51.8)
Cycle 3, n=26,29,11
70.84
(46.9)
74.04
(73.0)
69.83
(36.6)
53. Secondary Outcome
TitleCmax of Cys-mcMMAF Following IV Dose of GSK2857916 in Participants With RRMM
DescriptionBlood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods.
Time FrameCycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)

Outcome Measure Data

Analysis Population Description
Full PK Population. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants959924
Cycle 1, n=27,20,19
0.903
(63.9)
1.148
(64.7)
1.017
(61.4)
Cycle 3, n=26,29,11
0.660
(52.3)
0.749
(66.2)
0.656
(47.6)
54. Secondary Outcome
TitleTmax of Cys-mcMMAF Following IV Dose of GSK2857916 in Participants With RRMM
DescriptionBlood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods.
Time FrameCycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)

Outcome Measure Data

Analysis Population Description
Full PK Population. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants959924
Cycle 1, n=27,20,19
22.830
23.835
24.080
Cycle 3, n=26,29,11
23.235
22.570
22.780
55. Secondary Outcome
Titlet1/2 of Cys-mcMMAF Following IV Dose of GSK2857916 in Participants With RRMM
DescriptionBlood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods.
Time FrameCycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)

Outcome Measure Data

Analysis Population Description
Full PK Population. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants959924
Cycle 1, n=27,20,19
NA
(NA)
NA
(NA)
NA
(NA)
Cycle 3, n=26,29,11
NA
(NA)
NA
(NA)
NA
(NA)
56. Secondary Outcome
TitleNumber of Participants With at Least One Confirmed Positive Post-Baseline Anti-drug Antibody (ADA) Result
DescriptionSerum 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 tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for the specificity using the confirmation assay. Samples that confirmed positive in the confirmation assay were reported as 'positive'. Confirmed positive ADA samples were further characterized in the titration assay to quasi-quantitate the amount of ADA in the sample. Additionally, confirmed positive ADA samples were also tested in a validated neutralizing antibody assay to determine the potential neutralizing activity of the ADA.
Time FrameUp to 48 weeks

Outcome Measure Data

Analysis Population Description
Full Safety Population. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population. Only those participants with data available at the specified data points were analyzed.
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants899222
Count of Participants [Participants]
2
2.1%
0
0%
0
0%
57. Secondary Outcome
TitleTiters of Anti-drug Antibodies Against GSK2857916
DescriptionSerum 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. Titers of anti-drug antibodies against GSK2857916 is presented. No participant was found with positive results for ADA test in arms; GSK2857916 3.4 mg/kg (Frozen liquid) and GSK2857916 3.4 mg/kg (Lyophilized). Hence, titer values are not presented for both these arms.
Time FrameUp to 48 weeks

Outcome Measure Data

Analysis Population Description
Full Safety Population. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population. Only those participants with data available at the specified data points were analyzed.
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants200
Mean (Standard Deviation) [Titers]
100
(0)
58. Secondary Outcome
TitleNumber of Participants With Symptomatic AEs Measured by Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
DescriptionThe PRO-CTCAE is a patient-reported outcome measure developed to evaluate symptomatic toxicity in participants on cancer clinical trials. It included symptomatic toxicities drawn from the CTCAE like blurred vision (BV), chills, constipation, decreased appetite (DA), fatigue, general pain (GP), heart palpitations (HP), mouth/throat (M/T) sores, nausea, nosebleed, shortness of breath (SB), vomiting and watery eyes (WE). Items were scored individually on a 0 to 4 scale for severity, frequency and interference. Number of participants with symptomatic AEs (those who had a maximum post-Baseline rating greater than 0, example; 1, 2, 3, or 4) measured by PRO-CTCAE are presented.
Time FrameUp to 48 weeks

Outcome Measure Data

Analysis Population Description
Full Safety Population. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population.
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants959924
BV
58
59.8%
63
63.6%
18
72%
Chills
38
39.2%
33
33.3%
11
44%
Constipation
39
40.2%
43
43.4%
15
60%
DA
59
60.8%
61
61.6%
16
64%
Fatigue
80
82.5%
85
85.9%
21
84%
GP
76
78.4%
77
77.8%
19
76%
HP
31
32%
28
28.3%
12
48%
M/T sores
24
24.7%
21
21.2%
7
28%
Nausea
42
43.3%
45
45.5%
11
44%
Nosebleed
16
16.5%
32
32.3%
4
16%
SB
57
58.8%
52
52.5%
16
64%
Vomiting
15
15.5%
23
23.2%
4
16%
WE
48
49.5%
53
53.5%
18
72%
59. Secondary Outcome
TitleWorst Change From Baseline in National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) Overall Composite Score
DescriptionThe NEI-VFQ-25 consisted of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question to assess the impact of ocular toxicity on visual function. Items were coded to a 0 to 100 scale and averaged to calculate domains. Domain scores ranged from 0 to 100; higher scores are better. Therefore, increase in score means improvement. Baseline was defined as latest pre-dose assessment (Day 1) 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 worst-case post Baseline is presented.
Time FrameBaseline (Day 1) and up to Week 48

Outcome Measure Data

Analysis Population Description
Full Safety Population. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population. Only those participants with data available at the specified data points were analyzed.
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants829022
Mean (Standard Deviation) [Scores on a scale]
-18.8
(22.00)
-17.6
(21.13)
-21.4
(23.71)
60. Secondary Outcome
TitleWorst Change From Baseline in Ocular Surface Disease Index (OSDI) Total Score
DescriptionThe OSDI is a 12-item questionnaire designed to assess both the frequency of dry eye symptoms and their impact on vision-related functioning. The total OSDI score was calculated as (sum of scores for all questions answered*100) divided by (total number of questions answered*4). Domain scores ranged from 0 to 100; lower scores are better. Therefore, decrease in score from Baseline means improvement. Baseline was defined as latest pre-dose assessment (Day 1) 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 worst-case post Baseline is presented.
Time FrameBaseline (Day 1) and up to Week 48

Outcome Measure Data

Analysis Population Description
Full Safety Population. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population. Only those participants with data available at the specified data points were analyzed.
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants829122
Mean (Standard Deviation) [Scores on a scale]
25.4
(28.99)
25.1
(28.10)
34.3
(29.57)
61. Secondary Outcome
TitleChange From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core Module (EORTC QLQ-C30) Score
DescriptionThe EORTC QLQ-C30 includes 30-items with single and multi-item scales. These included five functional scales (physical functioning [PF], role functioning [RF], cognitive functioning [CF], emotional functioning [EF] and social functioning [SF]), three symptom scales (fatigue, pain and nausea/vomiting [N/V]), a global health status (GHS)/ Quality-of-Life (QoL) scale, and six single items (constipation, diarrhea, insomnia, dyspnea, appetite loss [AL] and financial difficulties [FD]). Response options are 1 to 4. Scores were averaged and transformed to 0 to 100, a high score for functional scales/ GHS/QoL represent better functioning ability or health-related quality-of-life (HRQoL), whereas a high score for symptom scales/ single items represent significant symptomatology. Baseline was defined as latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time FrameBaseline (Day 1) and Week 07, Week 13, Week 19, Week 25, Week 31, Week 37 and Week 43

Outcome Measure Data

Analysis Population Description
Full Analysis Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants464617
GHS/QoL,Week 07,n=46,46,17
0.4
(20.18)
-4.7
(18.23)
1.5
(23.80)
GHS/QoL,Week 13,n=29,28,16
-3.2
(18.42)
5.7
(16.36)
1.0
(14.23)
GHS/QoL,Week 19,n=19,26,10
-2.2
(13.84)
1.9
(18.30)
-0.0
(12.42)
GHS/QoL,Week 25,n=19,23,4
-4.4
(16.52)
-2.5
(20.94)
8.3
(11.79)
GHS/QoL,Week 31,n=12,14,0
-2.1
(12.37)
8.9
(17.13)
GHS/QoL,Week 37,n=4,3,0
-2.1
(4.17)
11.1
(12.73)
GHS/QoL,Week 43,n=0,2,0
25.0
(0.00)
PF,Week 07,n=46,46,17
5.1
(15.34)
-1.6
(21.78)
-5.5
(24.18)
PF,Week 13,n=29,28,16
0.7
(14.62)
6.4
(15.02)
-12.5
(23.84)
PF,Week 19,n=19,26,10
0.4
(13.78)
4.9
(24.77)
-4.0
(14.81)
PF,Week 25,n=19,23,4
1.8
(12.34)
5.5
(25.08)
3.3
(12.77)
PF,Week 31,n=12,14,0
-1.1
(8.45)
9.0
(18.42)
PF,Week 37,n=4,3,0
6.7
(9.43)
22.2
(34.21)
PF,Week 43,n=0,2,0
43.3
(23.57)
RF,Week 07,n=46,46,17
0.7
(33.88)
-8.3
(32.35)
-7.8
(25.08)
RF,Week 13,n=29,28,16
2.3
(33.55)
-0.6
(33.48)
-6.3
(30.96)
RF,Week 19,n=19,26,10
-4.4
(31.35)
-3.2
(30.56)
-5.0
(23.64)
RF,Week 25,n=19,23,4
2.6
(33.45)
0.0
(32.57)
0.0
(36.00)
RF,Week 31,n=12,14,0
13.9
(22.29)
1.2
(32.99)
RF,Week 37,n=4,3,0
4.2
(8.33)
27.8
(34.69)
RF,Week 43,n=0,2,0
33.3
(47.14)
EF,Week 07,n=46,46,17
1.8
(19.08)
1.1
(27.31)
-4.4
(21.27)
EF,Week 13,n=29,28,16
-2.0
(23.00)
2.4
(28.41)
-9.4
(23.35)
EF,Week 19,n=19,26,10
0.4
(19.93)
1.9
(20.59)
-1.7
(21.08)
EF,Week 25,n=19,23,4
-4.8
(21.75)
4.0
(20.39)
0.0
(18.00)
EF,Week 31,n=12,14,0
2.1
(21.94)
4.2
(26.70)
EF,Week 37,n=4,3,0
4.2
(8.33)
25.0
(36.32)
EF,Week 43,n=0,2,0
45.8
(41.25)
CF,Week 07,n=46,46,17
4.7
(20.98)
-2.2
(21.26)
-1.0
(20.81)
CF,Week 13,n=29,28,16
2.3
(23.45)
-0.6
(16.03)
-15.6
(27.53)
CF,Week 19,n=19,26,10
-1.8
(26.58)
-0.6
(23.32)
-6.7
(21.08)
CF,Week 25,n=19,23,4
-1.8
(28.27)
1.4
(21.27)
-4.2
(20.97)
CF,Week 31,n=12,14,0
9.7
(25.08)
-0.0
(18.49)
CF,Week 37,n=4,3,0
8.3
(28.87)
11.1
(19.25)
CF,Week 43,n=0,2,0
16.7
(23.57)
SF,Week 07,n=46,46,17
4.7
(29.12)
0.7
(32.76)
-1.0
(33.58)
SF,Week 13,n=29,28,16
-4.0
(28.75)
3.6
(31.54)
-7.3
(31.01)
SF,Week 19,n=19,26,10
-6.1
(28.44)
4.5
(28.50)
-6.7
(28.54)
SF,Week 25,n=19,23,4
-7.9
(26.86)
13.8
(22.84)
-0.0
(36.00)
SF,Week 31,n=12,14,0
2.8
(13.91)
21.4
(30.26)
SF,Week 37,n=4,3,0
-4.2
(15.96)
38.9
(25.46)
SF,Week 43,n=0,2,0
66.7
(47.14)
Fatigue,Week 07,n=46,46,17
-4.3
(22.03)
0.5
(23.07)
-5.2
(20.83)
Fatigue,Week 13,n=29,28,16
-7.7
(23.78)
-9.1
(22.44)
-1.4
(24.97)
Fatigue,Week 19,n=19,26,10
-0.6
(22.67)
0.9
(18.03)
-11.1
(15.71)
Fatigue,Week 25,n=19,23,4
4.7
(23.52)
-2.4
(21.70)
-2.8
(10.64)
Fatigue,Week 31,n=12,14,0
-0.0
(21.71)
-12.7
(19.90)
Fatigue,Week 37,n=4,3,0
0.0
(9.07)
-25.9
(35.72)
Fatigue,Week 43,n=0,2,0
-44.4
(62.85)
N/V,Week 07,n=46,46,17
2.2
(14.32)
5.1
(17.17)
2.0
(14.29)
N/V,Week 13,n=29,28,16
2.3
(13.16)
2.4
(8.74)
7.3
(25.80)
N/V,Week 19,n=19,26,10
-1.8
(15.61)
1.3
(12.40)
1.7
(5.27)
N/V,Week 25,n=19,23,4
5.3
(12.49)
-0.7
(12.79)
0.0
(0.00)
N/V,Week 31,n=12,14,0
-4.2
(7.54)
2.4
(6.05)
N/V,Week 37,n=4,3,0
0.0
(0.00)
0.0
(0.00)
N/V,Week 43,n=0,2,0
0.0
(0.00)
Pain,Week 07,n=46,46,17
-4.7
(27.37)
0.7
(25.81)
8.8
(28.33)
Pain,Week 13,n=29,28,16
-4.0
(26.97)
-4.2
(26.30)
5.2
(27.02)
Pain,Week 19,n=19,26,10
4.4
(19.12)
-3.8
(27.61)
1.7
(30.88)
Pain,Week 25,n=19,23,4
3.5
(18.07)
-1.4
(24.57)
-12.5
(20.97)
Pain,Week 31,n=12,14,0
5.6
(17.88)
-3.6
(18.70)
Pain,Week 37,n=4,3,0
12.5
(15.96)
-11.1
(19.25)
Pain,Week 43,n=0,2,0
-16.7
(47.14)
Dyspnoea,Week 07,n=46,46,17
-2.2
(21.55)
1.4
(13.98)
-7.8
(18.74)
Dyspnoea,Week 13,n=29,28,16
-1.1
(18.86)
-0.0
(18.14)
2.1
(30.96)
Dyspnoea,Week 19,n=19,26,10
-5.3
(20.07)
6.4
(21.12)
-16.7
(28.33)
Dyspnoea,Week 25,n=19,23,4
-1.8
(20.71)
4.3
(18.27)
8.3
(31.91)
Dyspnoea,Week 31,n=12,14,0
-11.1
(16.41)
0.0
(18.49)
Dyspnoea,Week 37,n=4,3,0
-16.7
(19.25)
11.1
(19.25)
Dyspnoea,Week 43,n=0,2,0
0.0
(0.00)
Insomnia,Week 07,n=46,46,17
-6.5
(30.32)
-1.4
(25.29)
-0.0
(23.57)
Insomnia,Week 13,n=29,28,16
0.0
(26.73)
-2.4
(25.55)
-0.0
(34.43)
Insomnia,Week 19,n=19,26,10
-8.8
(24.45)
-1.3
(27.46)
-13.3
(35.83)
Insomnia,Week 25,n=19,23,4
-5.3
(33.82)
-7.2
(22.38)
-8.3
(31.91)
Insomnia,Week 31,n=12,14,0
-22.2
(29.59)
-9.5
(35.63)
Insomnia,Week 37,n=4,3,0
-16.7
(19.25)
-11.1
(19.25)
Insomnia,Week 43,n=0,2,0
-16.7
(23.57)
AL,Week 07,n=46,46,17
5.1
(25.31)
3.6
(27.42)
2.0
(27.56)
AL,Week 13,n=29,28,16
8.0
(29.08)
-1.2
(26.42)
12.5
(26.87)
AL,Week 19,n=19,26,10
0.0
(24.85)
3.8
(33.10)
-3.3
(10.54)
AL,Week 25,n=19,23,4
7.0
(32.54)
-5.8
(21.68)
-8.3
(16.67)
AL,Week 31,n=12,14,0
-5.6
(12.97)
2.4
(20.52)
AL,Week 37,n=4,3,0
-8.3
(16.67)
11.1
(19.25)
AL,Week 43,n=0,2,0
0.0
(0.00)
Constipation,Week 07,n=46,46,17
-0.0
(21.08)
-2.2
(17.78)
-7.8
(25.08)
Constipation,Week 13,n=29,28,16
0.0
(25.20)
-4.8
(19.70)
8.3
(31.03)
Constipation,Week 19,n=19,26,10
-7.0
(21.02)
-1.3
(22.07)
-3.3
(18.92)
Constipation,Week 25,n=19,23,4
-3.5
(15.29)
-1.4
(18.74)
0.0
(27.22)
Constipation,Week 31,n=12,14,0
-5.6
(12.97)
0.0
(13.07)
Constipation,Week 37,n=4,3,0
0.0
(0.00)
0.0
(0.00)
Constipation,Week 43,n=0,2,0
0.0
(0.00)
Diarrhoea,Week 07,n=46,46,17
-2.9
(27.06)
-1.4
(27.18)
-2.0
(24.92)
Diarrhoea,Week 13,n=29,28,16
0.0
(25.20)
-6.0
(20.39)
4.2
(31.91)
Diarrhoea,Week 19,n=19,26,10
1.8
(26.00)
-2.6
(24.81)
-3.3
(18.92)
Diarrhoea,Week 25,n=19,23,4
1.8
(28.27)
-7.2
(33.27)
-8.3
(16.67)
Diarrhoea,Week 31,n=12,14,0
-5.6
(23.92)
-11.9
(30.96)
Diarrhoea,Week 37,n=4,3,0
8.3
(16.67)
0.0
(0.00)
Diarrhoea,Week 43,n=0,2,0
33.3
(0.00)
FD,Week 07,n=46,46,17
-5.1
(26.26)
2.9
(25.17)
0.0
(16.67)
FD,Week 13,n=29,28,16
-4.6
(23.10)
4.8
(19.70)
10.4
(20.07)
FD,Week 19,n=19,26,10
-7.0
(21.02)
3.8
(27.21)
10.0
(22.50)
FD,Week 25,n=19,23,4
-3.5
(26.98)
-1.4
(15.82)
8.3
(16.67)
FD,Week 31,n=12,14,0
-8.3
(25.13)
-2.4
(20.52)
FD,Week 37,n=4,3,0
0.0
(0.00)
-11.1
(19.25)
FD,Week 43,n=0,2,0
0.0
(47.14)
62. Secondary Outcome
TitleChange From Baseline in EORTC QLQ 20-item Multiple Myeloma Module (MY20) Score
DescriptionThe EORTC QLQ-MY20 is a supplement to the QLQ-C30 instrument used in participants with multiple myeloma. The module comprised of 20 questions that addressed four myeloma-specific HRQoL domains: disease symptoms (DS), side effects of treatment (SET), future perspective (FP) and body image (BI). Responses are 1 to 4. Scores were averaged and scales were transformed to 0 to 100 scale. A high score for disease symptoms and side effects of treatment represented a high level of symptomatology or problems, whereas a high score for future perspective and body image represented better outcomes. Baseline was defined as latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time FrameBaseline (Day 1) and Week 07, Week 13, Week 19, Week 25, Week 31, Week 37 and Week 43

Outcome Measure Data

Analysis Population Description
Full Analysis Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
Measure Participants454416
FP,Week 07,n=45,44,16
3.0
(25.67)
3.3
(29.70)
8.3
(24.51)
FP,Week 13,n=28,27,15
-2.0
(24.39)
8.6
(24.13)
-2.2
(27.28)
FP,Week 19,n=18,23,10
3.7
(22.87)
9.2
(21.10)
3.3
(27.24)
FP,Week 25,n=18,23,4
0.6
(26.81)
13.5
(29.39)
13.9
(40.95)
FP,Week 31,n=11,14,0
8.1
(17.98)
21.4
(27.38)
FP,Week 37,n=3,3,0
14.8
(23.13)
51.9
(12.83)
FP,Week 43,n=0,2,0
55.6
(15.71)
BI,Week 07,n=45,44,16
3.7
(22.72)
8.3
(27.02)
4.2
(43.67)
BI,Week 13,n=28,27,15
6.0
(25.75)
6.2
(35.85)
-4.4
(37.52)
BI,Week 19,n=18,23,10
5.6
(23.57)
5.8
(23.89)
-3.3
(42.89)
BI,Week 25,n=18,23,4
7.4
(24.40)
15.9
(31.57)
16.7
(57.74)
BI,Week 31,n=11,14,0
6.1
(20.10)
16.7
(33.97)
BI,Week 37,n=3,3,0
0.0
(0.00)
22.2
(19.25)
BI,Week 43,n=0,2,0
16.7
(23.57)
DS,Week 07,n=45,44,16
-2.3
(19.84)
-1.1
(17.96)
-2.8
(12.17)
DS,Week 13,n=28,27,15
-1.0
(16.22)
-6.2
(24.18)
1.1
(25.65)
DS,Week 19,n=18,23,10
0.9
(14.91)
-6.5
(14.67)
-1.7
(20.63)
DS,Week 25,n=18,23,4
0.9
(16.20)
-3.6
(17.78)
-0.0
(28.33)
DS,Week 31,n=11,14,0
-3.0
(11.75)
-10.7
(21.29)
DS,Week 37,n=3,3,0
-1.9
(8.49)
-24.1
(27.40)
DS,Week 43,n=0,2,0
-44.4
(39.28)
SET,Week 07,n=45,44,16
1.5
(9.41)
0.4
(13.49)
0.2
(15.49)
SET,Week 13,n=28,27,15
2.0
(10.44)
-3.0
(14.17)
6.8
(23.69)
SET,Week 19,n=18,23,10
0.0
(10.40)
-0.3
(10.69)
0.9
(9.04)
SET,Week 25,n=18,23,4
3.7
(8.48)
0.1
(13.10)
0.9
(6.33)
SET,Week 31,n=11,14,0
1.9
(6.44)
-2.1
(14.59)
SET,Week 37,n=3,3,0
0.0
(3.70)
-21.6
(24.45)
SET,Week 43,n=0,2,0
-28.3
(34.83)

Adverse Events

Time FrameSerious adverse events (SAEs) and common (>=5%) non-serious AEs were collected from the start of study treatment until maximum of 48 weeks
Adverse Event Reporting Description SAEs and common non-serious AEs were reported for the Full Safety Population which comprised of all participants who received atleast 1 dose of study treatment(frozen liquid or lyophilized powder). 3 out of 221 participants did not receive any study treatment and thus, were excluded from reporting of SAEs and common non-serious AEs. All-cause mortality is reported for Full Analysis Population(221)which comprised of all randomized participants whether or not randomized treatment was administered.
Arm/Group TitleGSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Arm/Group DescriptionParticipants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 11 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of 10 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of 8 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
All Cause Mortality
GSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total32/97 (33%) 31/99 (31.3%) 4/25 (16%)
Serious Adverse Events
GSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total38/95 (40%) 47/99 (47.5%) 15/24 (62.5%)
Blood and lymphatic system disorders
Thrombocytopenia1/95 (1.1%) 22/99 (2%) 23/24 (12.5%) 3
Febrile neutropenia0/95 (0%) 03/99 (3%) 30/24 (0%) 0
Hyperviscosity syndrome0/95 (0%) 02/99 (2%) 20/24 (0%) 0
Anaemia1/95 (1.1%) 10/99 (0%) 00/24 (0%) 0
Pancytopenia0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Cardiac disorders
Cardiac arrest1/95 (1.1%) 11/99 (1%) 10/24 (0%) 0
Atrial fibrillation0/95 (0%) 00/99 (0%) 01/24 (4.2%) 1
Mitral valve disease1/95 (1.1%) 10/99 (0%) 00/24 (0%) 0
Pericardial effusion0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Pericarditis0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Tachycardia1/95 (1.1%) 10/99 (0%) 00/24 (0%) 0
Eye disorders
Keratopathy0/95 (0%) 00/99 (0%) 01/24 (4.2%) 1
Gastrointestinal disorders
Gastrointestinal haemorrhage1/95 (1.1%) 11/99 (1%) 10/24 (0%) 0
Vomiting1/95 (1.1%) 11/99 (1%) 10/24 (0%) 0
Ascites1/95 (1.1%) 10/99 (0%) 00/24 (0%) 0
Colitis0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Constipation1/95 (1.1%) 10/99 (0%) 00/24 (0%) 0
Diarrhoea1/95 (1.1%) 10/99 (0%) 00/24 (0%) 0
Gastric fibrosis1/95 (1.1%) 10/99 (0%) 00/24 (0%) 0
Haematochezia0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Large intestinal haemorrhage0/95 (0%) 00/99 (0%) 01/24 (4.2%) 1
Large intestinal obstruction0/95 (0%) 00/99 (0%) 01/24 (4.2%) 1
Pancreatitis0/95 (0%) 00/99 (0%) 01/24 (4.2%) 1
General disorders
Pyrexia6/95 (6.3%) 75/99 (5.1%) 60/24 (0%) 0
General physical health deterioration0/95 (0%) 02/99 (2%) 20/24 (0%) 0
Non-cardiac chest pain1/95 (1.1%) 10/99 (0%) 01/24 (4.2%) 1
Chest pain0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Fatigue0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Influenza like illness0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Immune system disorders
Haemophagocytic lymphohistiocytosis0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Infections and infestations
Pneumonia4/95 (4.2%) 412/99 (12.1%) 131/24 (4.2%) 1
Lung infection3/95 (3.2%) 32/99 (2%) 30/24 (0%) 0
Sepsis2/95 (2.1%) 22/99 (2%) 20/24 (0%) 0
Cellulitis1/95 (1.1%) 11/99 (1%) 10/24 (0%) 0
Escherichia urinary tract infection0/95 (0%) 02/99 (2%) 20/24 (0%) 0
Influenza0/95 (0%) 02/99 (2%) 20/24 (0%) 0
Pneumonia influenzal0/95 (0%) 01/99 (1%) 11/24 (4.2%) 1
Staphylococcal sepsis2/95 (2.1%) 20/99 (0%) 00/24 (0%) 0
Upper respiratory tract infection0/95 (0%) 02/99 (2%) 20/24 (0%) 0
Vascular device infection2/95 (2.1%) 20/99 (0%) 00/24 (0%) 0
Brain abscess0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Device related infection1/95 (1.1%) 10/99 (0%) 00/24 (0%) 0
Enterocolitis infectious1/95 (1.1%) 10/99 (0%) 00/24 (0%) 0
Escherichia bacteraemia0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Escherichia sepsis0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Herpes simplex pneumonia1/95 (1.1%) 10/99 (0%) 00/24 (0%) 0
Lower respiratory tract infection0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Nocardiosis0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Otitis media0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Pneumonia legionella0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Pneumonia respiratory syncytial viral0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Sinusitis0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Staphylococcal bacteraemia0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Staphylococcal infection0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Viral infection0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Injury, poisoning and procedural complications
Infusion related reaction3/95 (3.2%) 42/99 (2%) 20/24 (0%) 0
Spinal compression fracture1/95 (1.1%) 11/99 (1%) 10/24 (0%) 0
Clavicle fracture0/95 (0%) 00/99 (0%) 01/24 (4.2%) 1
Fall1/95 (1.1%) 10/99 (0%) 00/24 (0%) 0
Fracture1/95 (1.1%) 10/99 (0%) 00/24 (0%) 0
Humerus fracture1/95 (1.1%) 10/99 (0%) 00/24 (0%) 0
Subdural haematoma0/95 (0%) 00/99 (0%) 01/24 (4.2%) 1
Tibia fracture1/95 (1.1%) 10/99 (0%) 00/24 (0%) 0
Upper limb fracture0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Investigations
Alanine aminotransferase increased0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Aspartate aminotransferase increased0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Blood lactate dehydrogenase increased0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Electrocardiogram T wave inversion1/95 (1.1%) 10/99 (0%) 00/24 (0%) 0
Metabolism and nutrition disorders
Hypercalcaemia4/95 (4.2%) 40/99 (0%) 01/24 (4.2%) 1
Dehydration0/95 (0%) 00/99 (0%) 02/24 (8.3%) 2
Hypokalaemia2/95 (2.1%) 20/99 (0%) 00/24 (0%) 0
Hyponatraemia1/95 (1.1%) 10/99 (0%) 01/24 (4.2%) 1
Hyperglycaemia0/95 (0%) 00/99 (0%) 01/24 (4.2%) 1
Hypocalcaemia1/95 (1.1%) 10/99 (0%) 00/24 (0%) 0
Hypomagnesaemia1/95 (1.1%) 10/99 (0%) 00/24 (0%) 0
Hypophosphataemia1/95 (1.1%) 10/99 (0%) 00/24 (0%) 0
Musculoskeletal and connective tissue disorders
Back pain1/95 (1.1%) 11/99 (1%) 10/24 (0%) 0
Muscular weakness1/95 (1.1%) 10/99 (0%) 01/24 (4.2%) 1
Osteolysis0/95 (0%) 02/99 (2%) 20/24 (0%) 0
Pathological fracture0/95 (0%) 02/99 (2%) 20/24 (0%) 0
Arthritis0/95 (0%) 00/99 (0%) 01/24 (4.2%) 1
Bone pain1/95 (1.1%) 10/99 (0%) 00/24 (0%) 0
Haematoma muscle0/95 (0%) 00/99 (0%) 01/24 (4.2%) 1
Lumbar spinal stenosis0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Osteonecrosis of jaw0/95 (0%) 00/99 (0%) 01/24 (4.2%) 1
Pain in extremity0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Spinal osteoarthritis0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Basal cell carcinoma0/95 (0%) 00/99 (0%) 01/24 (4.2%) 1
Nervous system disorders
Cerebral haemorrhage0/95 (0%) 02/99 (2%) 20/24 (0%) 0
Cognitive disorder0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Headache0/95 (0%) 00/99 (0%) 01/24 (4.2%) 1
Lethargy1/95 (1.1%) 10/99 (0%) 00/24 (0%) 0
Posterior reversible encephalopathy syndrome1/95 (1.1%) 10/99 (0%) 00/24 (0%) 0
Seizure1/95 (1.1%) 10/99 (0%) 00/24 (0%) 0
Spinal cord compression0/95 (0%) 00/99 (0%) 01/24 (4.2%) 1
Product Issues
Device dislocation0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Psychiatric disorders
Confusional state1/95 (1.1%) 10/99 (0%) 00/24 (0%) 0
Delirium1/95 (1.1%) 10/99 (0%) 00/24 (0%) 0
Renal and urinary disorders
Acute kidney injury2/95 (2.1%) 21/99 (1%) 10/24 (0%) 0
Renal failure1/95 (1.1%) 10/99 (0%) 00/24 (0%) 0
Renal impairment1/95 (1.1%) 10/99 (0%) 00/24 (0%) 0
Urinary retention0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Respiratory, thoracic and mediastinal disorders
Pleural effusion2/95 (2.1%) 21/99 (1%) 11/24 (4.2%) 1
Epistaxis1/95 (1.1%) 12/99 (2%) 20/24 (0%) 0
Cough0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Dyspnoea1/95 (1.1%) 10/99 (0%) 00/24 (0%) 0
Respiratory failure1/95 (1.1%) 10/99 (0%) 00/24 (0%) 0
Vascular disorders
Haematoma0/95 (0%) 01/99 (1%) 11/24 (4.2%) 1
Aortic stenosis0/95 (0%) 01/99 (1%) 10/24 (0%) 0
Hypertension1/95 (1.1%) 10/99 (0%) 00/24 (0%) 0
Other (Not Including Serious) Adverse Events
GSK2857916 2.5 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Frozen Liquid)GSK2857916 3.4 mg/kg (Lyophilized)
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total93/95 (97.9%) 96/99 (97%) 24/24 (100%)
Blood and lymphatic system disorders
Thrombocytopenia19/95 (20%) 2643/99 (43.4%) 598/24 (33.3%) 11
Anaemia22/95 (23.2%) 2537/99 (37.4%) 496/24 (25%) 12
Neutropenia6/95 (6.3%) 1119/99 (19.2%) 271/24 (4.2%) 2
Leukopenia9/95 (9.5%) 97/99 (7.1%) 80/24 (0%) 0
Lymphopenia6/95 (6.3%) 65/99 (5.1%) 51/24 (4.2%) 1
Eye disorders
Keratopathy67/95 (70.5%) 16274/99 (74.7%) 19722/24 (91.7%) 51
Vision blurred17/95 (17.9%) 2125/99 (25.3%) 337/24 (29.2%) 10
Dry eye11/95 (11.6%) 1118/99 (18.2%) 185/24 (20.8%) 8
Photophobia3/95 (3.2%) 35/99 (5.1%) 53/24 (12.5%) 3
Diplopia2/95 (2.1%) 34/99 (4%) 52/24 (8.3%) 2
Gastrointestinal disorders
Nausea23/95 (24.2%) 2532/99 (32.3%) 381/24 (4.2%) 1
Diarrhoea11/95 (11.6%) 1415/99 (15.2%) 152/24 (8.3%) 2
Vomiting6/95 (6.3%) 819/99 (19.2%) 190/24 (0%) 0
Constipation11/95 (11.6%) 129/99 (9.1%) 93/24 (12.5%) 4
General disorders
Fatigue15/95 (15.8%) 1626/99 (26.3%) 288/24 (33.3%) 9
Pyrexia18/95 (18.9%) 2122/99 (22.2%) 284/24 (16.7%) 5
Asthenia4/95 (4.2%) 410/99 (10.1%) 102/24 (8.3%) 2
Chills7/95 (7.4%) 74/99 (4%) 41/24 (4.2%) 1
Pain5/95 (5.3%) 55/99 (5.1%) 50/24 (0%) 0
Oedema peripheral3/95 (3.2%) 33/99 (3%) 33/24 (12.5%) 4
Infections and infestations
Upper respiratory tract infection7/95 (7.4%) 815/99 (15.2%) 193/24 (12.5%) 3
Urinary tract infection6/95 (6.3%) 75/99 (5.1%) 91/24 (4.2%) 1
Bronchitis5/95 (5.3%) 52/99 (2%) 20/24 (0%) 0
Nasopharyngitis1/95 (1.1%) 15/99 (5.1%) 60/24 (0%) 0
Injury, poisoning and procedural complications
Infusion related reaction14/95 (14.7%) 158/99 (8.1%) 91/24 (4.2%) 1
Rib fracture0/95 (0%) 01/99 (1%) 12/24 (8.3%) 2
Investigations
Aspartate aminotransferase increased19/95 (20%) 2024/99 (24.2%) 314/24 (16.7%) 4
Platelet count decreased15/95 (15.8%) 1814/99 (14.1%) 262/24 (8.3%) 2
Lymphocyte count decreased13/95 (13.7%) 1512/99 (12.1%) 132/24 (8.3%) 3
Blood creatinine increased10/95 (10.5%) 1111/99 (11.1%) 142/24 (8.3%) 2
Gamma-glutamyltransferase increased8/95 (8.4%) 813/99 (13.1%) 132/24 (8.3%) 2
Blood alkaline phosphatase increased8/95 (8.4%) 812/99 (12.1%) 120/24 (0%) 0
Neutrophil count decreased7/95 (7.4%) 89/99 (9.1%) 92/24 (8.3%) 2
White blood cell count decreased7/95 (7.4%) 810/99 (10.1%) 110/24 (0%) 0
Intraocular pressure increased6/95 (6.3%) 85/99 (5.1%) 55/24 (20.8%) 5
Blood lactate dehydrogenase increased4/95 (4.2%) 47/99 (7.1%) 84/24 (16.7%) 4
Alanine aminotransferase increased5/95 (5.3%) 55/99 (5.1%) 60/24 (0%) 0
Weight decreased8/95 (8.4%) 81/99 (1%) 11/24 (4.2%) 1
Blood creatine phosphokinase increased5/95 (5.3%) 73/99 (3%) 30/24 (0%) 0
C-reactive protein increased2/95 (2.1%) 25/99 (5.1%) 51/24 (4.2%) 1
Urine albumin/creatinine ratio increased2/95 (2.1%) 26/99 (6.1%) 60/24 (0%) 0
Bacterial test positive0/95 (0%) 00/99 (0%) 02/24 (8.3%) 2
Metabolism and nutrition disorders
Decreased appetite11/95 (11.6%) 1318/99 (18.2%) 204/24 (16.7%) 4
Hypercalcaemia9/95 (9.5%) 1016/99 (16.2%) 184/24 (16.7%) 5
Hypokalaemia6/95 (6.3%) 613/99 (13.1%) 133/24 (12.5%) 5
Hyponatraemia4/95 (4.2%) 411/99 (11.1%) 124/24 (16.7%) 4
Hyperuricaemia9/95 (9.5%) 148/99 (8.1%) 90/24 (0%) 0
Hypoalbuminaemia5/95 (5.3%) 510/99 (10.1%) 121/24 (4.2%) 1
Hypophosphataemia7/95 (7.4%) 107/99 (7.1%) 102/24 (8.3%) 2
Hypomagnesaemia5/95 (5.3%) 76/99 (6.1%) 61/24 (4.2%) 1
Hyperglycaemia3/95 (3.2%) 46/99 (6.1%) 72/24 (8.3%) 2
Hypocalcaemia4/95 (4.2%) 43/99 (3%) 32/24 (8.3%) 2
Musculoskeletal and connective tissue disorders
Back pain9/95 (9.5%) 1010/99 (10.1%) 105/24 (20.8%) 5
Arthralgia11/95 (11.6%) 117/99 (7.1%) 71/24 (4.2%) 1
Pain in extremity5/95 (5.3%) 511/99 (11.1%) 150/24 (0%) 0
Bone pain4/95 (4.2%) 59/99 (9.1%) 100/24 (0%) 0
Musculoskeletal pain5/95 (5.3%) 57/99 (7.1%) 81/24 (4.2%) 1
Musculoskeletal chest pain5/95 (5.3%) 56/99 (6.1%) 70/24 (0%) 0
Myalgia2/95 (2.1%) 23/99 (3%) 32/24 (8.3%) 2
Nervous system disorders
Headache9/95 (9.5%) 1014/99 (14.1%) 184/24 (16.7%) 4
Dizziness0/95 (0%) 06/99 (6.1%) 61/24 (4.2%) 1
Psychiatric disorders
Insomnia5/95 (5.3%) 51/99 (1%) 12/24 (8.3%) 2
Respiratory, thoracic and mediastinal disorders
Cough7/95 (7.4%) 718/99 (18.2%) 192/24 (8.3%) 2
Epistaxis7/95 (7.4%) 817/99 (17.2%) 200/24 (0%) 0
Dyspnoea5/95 (5.3%) 55/99 (5.1%) 51/24 (4.2%) 1
Skin and subcutaneous tissue disorders
Hyperhidrosis2/95 (2.1%) 21/99 (1%) 12/24 (8.3%) 2
Vascular disorders
Hypertension6/95 (6.3%) 79/99 (9.1%) 101/24 (4.2%) 1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Results Point of Contact

Name/TitleGSK Response Center
OrganizationGlaxoSmithKline
Phone866-435-7343
EmailGSKClinicalSupportHD@gsk.com
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT03525678
Other Study ID Numbers:
  • 205678
  • 2017-004810-25
First Posted:
May 16, 2018
Last Update Posted:
Oct 4, 2021
Last Verified:
Sep 1, 2021