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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03525678
Recruitment Status : Active, not recruiting
First Posted : May 16, 2018
Results First Posted : April 28, 2020
Last Update Posted : November 23, 2020
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

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 disease Intervention/treatment Phase
Multiple Myeloma Drug: Belantamab mafodotin frozen liquid Drug: Belantamab mafodotin lyophilized powder Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
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 : June 18, 2018
Actual Primary Completion Date : June 21, 2019
Estimated Study Completion Date : March 31, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/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.




Primary Outcome Measures :
  1. Overall Response Rate (ORR) by Independent Review Committee (IRC) (Full Analysis Population) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.



Information from the National Library of Medicine

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


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 10^9/L; Hemoglobin >=8.0 g/dL; Platelets>= 50 X 10^9/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.

Information from the National Library of Medicine

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

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03525678


Locations
Show Show 59 study locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
  Study Documents (Full-Text)

Documents provided by GlaxoSmithKline:
Study Protocol  [PDF] December 17, 2018
Statistical Analysis Plan  [PDF] July 16, 2019

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03525678    
Other Study ID Numbers: 205678
2017-004810-25 ( EudraCT Number )
First Posted: May 16, 2018    Key Record Dates
Results First Posted: April 28, 2020
Last Update Posted: November 23, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
Relapsed Refractory multiple myeloma
Antibody-drug conjugate
Patient-Reported Outcome Version of the Common Term Criteria for Adverse Events
Quality of Life Questionnaire 20-item Multiple Myeloma module
Multiple Myeloma
Quality of Life Questionnaire 30-item Core module
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases