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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03544281




Registration number
NCT03544281
Ethics application status
Date submitted
30/04/2018
Date registered
1/06/2018
Date last updated
29/07/2019

Titles & IDs
Public title
To Evaluate Safety, Tolerability, and Clinical Activity of the Antibody-drug Conjugate, GSK2857916 Administered in Combination With Lenalidomide Plus Dexamethasone (Arm A), or in Combination With Bortezomib Plus Dexamethasone (Arm B) in Participants With Relapsed/Refractory Multiple Myeloma (RRMM)
Scientific title
A Phase I/II, Open-label, Dose Escalation and Expansion Study to Evaluate Safety, Tolerability, and Clinical Activity of the Antibody-Drug Conjugate GSK2857916 Administered in Combination With Lenalidomide Plus Dexamethasone (Arm A), or Bortezomib Plus Dexamethasone (Arm B) in Participants With Relapsed / Refractory Multiple Myeloma - DREAMM-6
Secondary ID [1] 0 0
2017-004689-93
Secondary ID [2] 0 0
207497
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GSK2857916
Treatment: Drugs - Lenalidomide
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Bortezomib
Treatment: Drugs - GSK2857916

Experimental: Arm A, Part 1, GSK2857916 plus lenalidomide plus dexamethasone - Modified Toxicity Probability Interval (mTPI) design will be used to guide Part 1 dose escalation. Up to 3 dose levels of GSK2857916 (1.9 milligram/kilogram (mg/kg), 2.5 mg/kg; 3.4 mg/kg) and 2 alternate dosing schedules will be evaluated in combination with a fixed dose of Len/Dex. Based on data from Arm A, first dose investigated in Amendment 2 will be 1.9 mg/kg. Cohorts will be recruited in blocks of 3 participants and will enroll with at least 1 day between each participant's first dose of GSK2857916 to reduce risk of exceeding the maximum tolerated dose (MTD). For a move to the next dose level, dose-limiting toxicities (DLTs)- from 3 evaluable participants will be reviewed. Participants in Arm A will receive Len, 25 mg or 10 mg orally daily, on Days 1-21 of each 28-day cycle with Dex, 40 mgs weekly per oral (PO) on Days 1, 8, 15, and 22 of each cycle. Participants may continue treatment until PD, intolerable AEs, consent withdrawal, or death.

Experimental: Arm B, Part 1, GSK2857916 plus bortezomib plus dexamethasone - A mTPI design will guide Part 1 dose escalation. Up to 3 dose levels of GSK2857916 (2.5 mg/kg; 3.4 mg/kg; 1.9 mg/kg), and 2 alternate dosing schedules will be evaluated with a fixed dose of Bor/Dex. Cohorts will be recruited in blocks of 3 participants with up to 6 per dose level. Participants will enroll with at least 1 day between each participant's first dose of GSK2857916 to reduce the risk of exceeding MTD. To move to next dose level, at least 3 DLT evaluable participants will be reviewed. Participants in Arm B receive bortezomib, at a dose of 1.3 mg/m^2 (mg/square meters), approximately 1-hour post GSK2857916, on Days 1, 4, 8, and 11 of every 21-day cycle, for 8 cycles and dexamethasone at 20 mg PO, or intravenous (IV) on Days 1, 2, 4, 5, 8, 9, 11, and 12 of every 21-day cycle. Participants also receive an antiviral for up to 8-cycles. After 8 cycles of combination therapy participants will receive GSK2857916 monotherapy until PD, intolerable AEs, consent withdrawal, or death.

Experimental: Arm A, Part 2, GSK2857916, Expansion - Part 2 of Arm A will further evaluate the safety and preliminary clinical activity of GSK2857916 with Len/Dex to identify the optimal dose(s) and schedules for combination treatment of GSK2857916 when administered with Len/Dex. The participants in Arm A will receive GSK2857916 , on Day 1 of each 28-Day cycle. Participants in Arm A will receive lenalidomide, at dose of 25 mg or 10 mg orally daily, on Days 1-21 of each 28-day cycle; with dexamethasone at a dose of 40 mg or 20 mg once weekly, orally on Days 1, 8, 15, and 22 of each cycle.

Experimental: Arm B, Part 2, GSK2857916, Expansion - Part 2 of Arm B will further evaluate the safety and preliminary clinical activity of GSK2857916 with Bor/Dex to identify the optimal dose(s) and schedules for each arm of combination treatment of GSK2857916 when administered with Bor/Dex. The participants in Arm B will receive GSK2857916 , on Day 1 of each 21-Day cycle. Participants in Arm B will receive bortezomib, at a dose of 1.3 mg/m^2, subcutaneously (SC) or IV, given approximately 1 hour post GSK2857916, assuring participants stability, on Days 1, 4, 8, and 11 of every 21-day cycle, for 8 cycles; with dexamethasone at a dose of 20 mg orally, or IV on Days 1, 2, 4, 5, 8, 9, 11, and 12 of every 21-day cycle. Participants will also receive Acyclovir or other antiviral, for up to 8-cycles.


Treatment: Drugs: GSK2857916
Selected doses and schedules of GSK2857916, will be administered as infusion during Part 1 and Part 2, in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone respectively.

Treatment: Drugs: Lenalidomide
Lenalidomide will be administered as 25 or 10 mg, orally, with GSK2857916 and dexamethasone, during Part 1 and Part 2.

Treatment: Drugs: Dexamethasone
Dexamethasone will be administered as 20 or 40 mg, orally with GSK2857916, and lenalidomide or bortezomib, during Part 1 and Part 2 respectively.

Treatment: Drugs: Bortezomib
Bortezomib will be administered as 1.3 mg/m^2, as SC or IV, with GSK2857916 and dexamethasone, during Part 1 and Part 2 respectively.

Treatment: Drugs: GSK2857916
Selected dose levels and schedules of GSK2857916, will be administered in Part 2, as an infusion. It will be given with lenalidomide and dexamethasone, or with bortezomib and dexamethasone, during Part 2.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number (percentage[%]) of particpant's with DLTs, Part 1 - The number (%) of participant's with DLT's will be reported.
Timepoint [1] 0 0
Up to 4.5 years
Primary outcome [2] 0 0
Number (%) of participants with AE's and serious adverse events (SAEs), Part 1 - An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth defect and other situations which involve medical or scientific judgment, and is associated with liver injury and impaired liver function The number (%) of participant experiencing SAE and AEs during Part 1 of the study will be reported.
Timepoint [2] 0 0
Up to 4.5 years
Primary outcome [3] 0 0
Number (%) of participants with electrocardiogram (ECG) parameters of potential clinical importance (PCI), Part 1 - Twelve-lead ECGs, will be performed, with the participant at designated time points, using an ECG machine, after 5 minutes of rest. The number (%) of participants with PCI values, will be reported.
Timepoint [3] 0 0
Up to 4.5 years
Primary outcome [4] 0 0
Number (%) of participants with abnormal hematology parameters, Part 1 - Blood samples will be collected to measure platelets, white blood cell (WBC count), red blood cell (RBC) count, reticulocyte count, hemoglobin, hematocrit, RBC indices, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), basophils, eosinophils, lymphocytes, monocytes and neutrophils. The number (%) of participants with abnormal hematology parameters will be reported.
Timepoint [4] 0 0
Up to 4.5 years
Primary outcome [5] 0 0
Number (%) of participants with abnormal clinical chemistry parameters, Part 1 - Blood samples will be collected to measure blood urea nitrogen (BUN), creatinine, glucose, sodium, magnesium, potassium, chloride, Total carbon dioxide (CO2), phosphorous, calcium, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase, creatinine kinase (CK), total and direct bilirubin, uric acid, albumin, total protein, lactate dehydrogenase (LDH). The number (%) of participants with abnormal clinical chemistry parameters will be reported.
Timepoint [5] 0 0
Up to 4.5 years
Primary outcome [6] 0 0
Number (%) of participants with abnormal urinalysis parameters, Part 1 - Urine samples will be collected to measure specific gravity, potential of hydrogen (pH), glucose, protein, blood and ketones by dipstick method at specified time points. The number (%) of participants with abnormal urinalysis parameters will be reported.
Timepoint [6] 0 0
Up to 4.5 years
Primary outcome [7] 0 0
Number (%) of participants with vital signs of PCI, Part 1 - The number (%) of participants with vital signs of PCI, for systolic blood pressure (SBP), diastolic blood pressure (DBP), temperature and heart rate will be reported. Vitals will be measured after specific time points after at least 5 minutes of rest.
Timepoint [7] 0 0
Up to 4.5 years
Primary outcome [8] 0 0
Number (%) of participants with AEs and SAEs as a measure of safety in Part 2 - An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth defect and other situations which involve medical or scientific judgment, and is associated with liver injury and impaired liver function. The number (%) of participants experiencing SAE and AEs during Part 2 of the study will be reported.
Timepoint [8] 0 0
Up to 4.5 years
Primary outcome [9] 0 0
Summary of Overall Response Rate (ORR) as defined by the International Myeloma Working Group (IMWG) Uniform Response Criteria for multiple myeloma (MM), Part 2 - ORR defined as percentage (%) of participants achieving >=Partial Response (PR) as defined by the IMWG Uniform Response Criteria for MM.
Timepoint [9] 0 0
Up to 4.5 years
Secondary outcome [1] 0 0
Maximum plasma concentration (Cmax) for GSK2857916, Part 1, Treatment A - Serial blood samples will be collected for pharmacokinetic (PK) analysis.
Timepoint [1] 0 0
Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6 and pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 28 days)
Secondary outcome [2] 0 0
Area under the curve (AUC) for GSK2857916, Part 1, Treatment A - Serial blood samples will be collected for PK analysis.
Timepoint [2] 0 0
Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6; pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 28 days)
Secondary outcome [3] 0 0
Time to maximum plasma concentration (Tmax) for GSK2857916, Part 1, Treatment A - Serial blood samples will be collected for PK analysis.
Timepoint [3] 0 0
Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6 and pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 28 days)
Secondary outcome [4] 0 0
Serum half-life (t1/2) for GSK2857916, Part 1, Treatment A - Serial blood samples will be collected for PK analysis.
Timepoint [4] 0 0
Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6 and pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 28 days)
Secondary outcome [5] 0 0
Cmax for GSK2857916, Part 1, Treatment B - Serial blood samples will be collected for PK analysis.
Timepoint [5] 0 0
Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; Cycle 1 Day 8; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6; pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 21 days)
Secondary outcome [6] 0 0
AUC for GSK2857916, Part 1, Treatment B - Serial blood samples, will be collected for PK analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
Timepoint [6] 0 0
Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; Cycle 1 Day 8; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6; pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 21 days)
Secondary outcome [7] 0 0
Tmax for GSK2857916, Part 1, Treatment B - Serial blood samples, will be collected for PK analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
Timepoint [7] 0 0
Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; Cycle 1 Day 8; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6; pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 21 days)
Secondary outcome [8] 0 0
t1/2 for GSK2857916, Part 1, Treatment B - Serial blood samples, will be collected for PK analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
Timepoint [8] 0 0
Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; Cycle 1 Day 8; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6; pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 21 days)
Secondary outcome [9] 0 0
Cmax for GSK2857916, Part 2, Treatment A - Serial blood samples will be collected for PK analysis.
Timepoint [9] 0 0
Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6 and pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 28 days)
Secondary outcome [10] 0 0
AUC for GSK2857916, Part 2, Treatment A - Serial blood samples will be collected for PK analysis.
Timepoint [10] 0 0
Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6 and pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 28 days)
Secondary outcome [11] 0 0
Tmax for GSK2857916, Part 2, Treatment A - Serial blood samples will be collected for PK analysis.
Timepoint [11] 0 0
Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6 and pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 28 days)
Secondary outcome [12] 0 0
t1/2 for GSK2857916, Part 2, Treatment A - Serial blood samples will be collected for PK analysis.
Timepoint [12] 0 0
Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6 and pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 28 days)
Secondary outcome [13] 0 0
Cmax for GSK2857916, Part 2, Treatment B - Serial blood samples, will be collected for PK analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
Timepoint [13] 0 0
Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; Cycle 1 Day 8; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6; pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 21 days)
Secondary outcome [14] 0 0
AUC for GSK2857916, Part 2, Treatment B - Serial blood samples, will be collected for PK analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
Timepoint [14] 0 0
Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; Cycle 1 Day 8; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6; pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 21 days)
Secondary outcome [15] 0 0
Tmax for GSK2857916, Part 2, Treatment B - Serial blood samples, will be collected for PK analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
Timepoint [15] 0 0
Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; Cycle 1 Day 8; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6; pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 21 days)
Secondary outcome [16] 0 0
t1/2 for GSK2857916, Part 2, Treatment B - Serial blood samples, will be collected for PK analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
Timepoint [16] 0 0
Pre-dose and at 2 hour post-infusion on Day 1 Cycle 1; Cycle 1 Day 8; pre-dose and post-dose on Day 1 of Cycle 2, Cycle 3, Cycle 6; pre-dose on Day 1 of Cycle 9 and Cycle 12 (Each cycle is of 21 days)
Secondary outcome [17] 0 0
Cmax for Lenalidomide, Part 1, Treatment A - Serial blood samples will be collected for PK analysis.
Timepoint [17] 0 0
At pre-dose, and 0.5, 1, 2, and 4 hour post dose on Day 1 of Cycle 1 (each cycle is 28 days)
Secondary outcome [18] 0 0
AUC for Lenalidomide, Part 1, Treatment A - Serial blood samples will be collected for PK analysis.
Timepoint [18] 0 0
At pre-dose, and 0.5, 1, 2, and 4 hour post dose on Day 1 of Cycle 1 (each cycle is 28 days)
Secondary outcome [19] 0 0
Tmax for Lenalidomide, Part 1, Treatment A - Serial blood samples will be collected for PK analysis.
Timepoint [19] 0 0
At pre-dose, and 0.5, 1, 2, and 4 hour post dose on Day 1 of Cycle 1 (each cycle is 28 days)
Secondary outcome [20] 0 0
t1/2 for Lenalidomide, Part 1, Treatment A - Serial blood samples will be collected for PK analysis.
Timepoint [20] 0 0
At pre-dose, and 0.5, 1, 2, and 4 hour post dose on Day 1 of Cycle 1 (each cycle is 28 days)
Secondary outcome [21] 0 0
Cmax for Bortezomib, Part 1, Treatment B - Serial blood samples, will be collected for PK analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
Timepoint [21] 0 0
Pre-dose and 5, 15, 30 minutes and 1, 2, 4, 6, 10, 24, 48, 72 hours post-dose on Day 1 of Cycle 1 (Each cycle is of 21 days)
Secondary outcome [22] 0 0
AUC for Bortezomib, Part 1, Treatment B - Serial blood samples, will be collected for PK analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
Timepoint [22] 0 0
Pre-dose and 5, 15, 30 minutes and 1, 2, 4, 6, 10, 24, 48, 72 hours post-dose on Day 1 of Cycle 1 (Each cycle is of 21 days)
Secondary outcome [23] 0 0
Tmax for Bortezomib, Part 1, Treatment B - Serial blood samples, will be collected for PK analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
Timepoint [23] 0 0
Pre-dose and 5, 15, 30 minutes and 1, 2, 4, 6, 10, 24, 48, 72 hours post-dose on Day 1 of Cycle 1 (Each cycle is of 21 days)
Secondary outcome [24] 0 0
t1/2 for Bortezomib, Part 1, Treatment B - Serial blood samples, will be collected for PK analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
Timepoint [24] 0 0
Pre-dose and 5, 15, 30 minutes and 1, 2, 4, 6, 10, 24, 48, 72 hours post-dose on Day 1 of Cycle 1 (Each cycle is of 21 days)
Secondary outcome [25] 0 0
Cmax for Lenalidomide, Part 2, Treatment A - Serial blood samples will be collected for PK analysis.
Timepoint [25] 0 0
At pre-dose, and 0.5 hour, 1, 2, and 4 hour post dose on Day 1 of Cycle 1 (each cycle is 28 days)
Secondary outcome [26] 0 0
AUC for Lenalidomide, Part 2, Treatment A - Serial blood samples will be collected for PK analysis.
Timepoint [26] 0 0
At pre-dose, and 0.5 hour, 1, 2, and 4 hour post dose on Day 1 of Cycle 1 (each cycle is 28 days)
Secondary outcome [27] 0 0
Tmax for Lenalidomide, Part 2, Treatment A - Serial blood samples will be collected for PK analysis.
Timepoint [27] 0 0
At pre-dose, and 0.5 hour, 1, 2, and 4 hour post dose on Day 1 of Cycle 1 (each cycle is 28 days)
Secondary outcome [28] 0 0
t1/2 for Lenalidomide, Part 2, Treatment A - Serial blood samples will be collected for PK analysis.
Timepoint [28] 0 0
At pre-dose, and 0.5 hour, 1, 2, and 4 hour post dose on Day 1 of Cycle 1 (each cycle is 28 days)
Secondary outcome [29] 0 0
Cmax for Lenalidomide, Part 2, Treatment B - Serial blood samples will be collected for PK analysis.
Timepoint [29] 0 0
Pre-dose and 5, 15, 30 minutes and 1, 2, 4, 6, 10, 24, 48, 72 hours post-dose on Day 1 of Cycle 1 (Each cycle is of 21 days)
Secondary outcome [30] 0 0
AUC for Lenalidomide, Part 2, Treatment B - Serial blood samples will be collected for PK analysis.
Timepoint [30] 0 0
Pre-dose and 5, 15, 30 minutes and 1, 2, 4, 6, 10, 24, 48, 72 hours post-dose on Day 1 of Cycle 1 (Each cycle is of 21 days)
Secondary outcome [31] 0 0
Tmax for Lenalidomide, Part 2, Treatment B - Serial blood samples will be collected for PK analysis.
Timepoint [31] 0 0
Pre-dose and 5, 15, 30 minutes and 1, 2, 4, 6, 10, 24, 48, 72 hours post-dose on Day 1 of Cycle 1 (Each cycle is of 21 days)
Secondary outcome [32] 0 0
t1/2 for Lenalidomide, Part 2, Treatment B - Serial blood samples will be collected for PK analysis.
Timepoint [32] 0 0
Pre-dose and 5, 15, 30 minutes and 1, 2, 4, 6, 10, 24, 48, 72 hours post-dose on Day 1 of Cycle 1 (Each cycle is of 21 days)
Secondary outcome [33] 0 0
Number of participants with anti-drug antibodies (ADAs) against GSK2857916, Part 1, Treatment A - The number of participants with ADAs will be reported. All ADA samples will be collected prior to each infusion (at Cycle 1, 2, 3, 6, 9, 12) on the dosing days in Part 1, at the same time as the pre-dose GSK2857916, PK samples.
Timepoint [33] 0 0
Pre-dose on Day 1 of Cycle 1, 2, 3, 6, 9, 12 (Each cycle is of 28 days)
Secondary outcome [34] 0 0
Number of participants with ADAs, against GSK2857916, Part 1 treatment B - The number of participants with ADAs will be reported. All ADA samples will be collected prior to each infusion (at Cycle 1, 2, 3, 6, 9, 12) on the dosing days in Part 1, at the same time as the pre-dose GSK2857916, PK samples.
Timepoint [34] 0 0
Pre-dose on Day 1 of Cycle 1, 2, 3, 6, 9, 12 (Each cycle is of 21 days)
Secondary outcome [35] 0 0
Number of participants with ADAs, against GSK2857916, Part 2 Treatment A - The number of participants with ADAs will be reported. All ADA samples will be collected prior to each infusion (at Cycle 1, 2, 3, 6, 9, and Cycle 12) on the dosing days in Part 2 at the same time as the pre-dose GSK2857916 PK samples.
Timepoint [35] 0 0
Pre-dose on Day 1 of Cycle 1, 2, 3, 6, 9, 12 (Each cycle is of 28 days)
Secondary outcome [36] 0 0
Number of participants with ADAs, against GSK2857916, Part 2, Treatment B - The number of participants with ADAs will be reported. All ADA samples will be collected prior to each infusion (at Cycle 1, 2, 3, 6, 9, and Cycle 12) on the dosing days in Part 2 at the same time as the pre-dose GSK2857916 PK samples.
Timepoint [36] 0 0
Pre-dose on Day 1 of Cycle 1, 2, 3, 6, 9, 12 (Each cycle is of 21 days)
Secondary outcome [37] 0 0
Change from Baseline in symptoms and impacts as measured by Ocular Surface Disease Index (OSDI), Part 1 - 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 OSDI has demonstrated good reliability, validity, sensitivity, and specificity, and can be used as a complement to other clinical and subjective measures of dry eye disease by providing a quantifiable assessment of dry eye symptom frequency and the impact of these symptoms on vision-related functioning. The OSDI will be measured at every 4-weeks, for Treatment A and every 3-weeks, for Treatment B.
Timepoint [37] 0 0
Baseline and up to 4.5 years
Secondary outcome [38] 0 0
Change from Baseline in symptoms and impacts as measured by the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25), Part 1 - The NEI-VFQ-25, consists of a base set of 25 vision-targeted questions representing, 11 vision-related constructs, plus an additional single-item, general health rating question. These include, a global vision rating (1 item); difficulty with near vision activities (3 items); difficulty with distance vision activities (3 items); limitations in social functioning due to vision (2 items); role limitations due to vision (2 items); dependency on others due to vision (3 items); mental health symptoms due to vision (4 items); driving difficulties (3 items); limitations with peripheral vision (1 item), limitations with color vision (1 item); and Ocular pain (2 items). Scores will be measured, every 4-weeks, for Treatment and every 3-weeks, for Treatment B.
Timepoint [38] 0 0
Baseline and up to 4.5 years
Secondary outcome [39] 0 0
Change from Baseline in symptoms and impacts as measured by Patient-Reported Outcome Version of the Common Term Criteria for Adverse Events (PRO-CTCAE), Part 1 - The PRO-CTCAE is a participant-reported outcome measure developed to evaluate symptomatic toxicity in participants on cancer clinical trials. The PRO-CTCAE includes an item library of 124 items representing 80 symptomatic toxicities drawn from the CTCAE.
Timepoint [39] 0 0
Baseline and up to 4.5 years
Secondary outcome [40] 0 0
Change from Baseline in symptoms and impacts as measured by OSDI, Part 2 - The ocular surface disease index (OSDI), is a 12-item questionnaire designed to assess both the frequency of dry eye symptoms and their impact on vision-related functioning. The OSDI has demonstrated good reliability, validity, sensitivity, and specificity, and can be used as a complement to other clinical and subjective measures of dry eye disease by providing a quantifiable assessment of dry eye symptom frequency and the impact of these symptoms on vision-related functioning. The OSDI will be measured at every 4-weeks, for Treatment A and every 3-weeks, for Treatment B.
Timepoint [40] 0 0
Baseline and up to 4.5 years
Secondary outcome [41] 0 0
Change from Baseline in symptoms and impacts as measured by NEI-VFQ-25, Part 2 - The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) consists of a base set of 25 vision-targeted questions representing, 11 vision-related constructs, plus an additional single-item, general health rating question. These include, a global vision rating (1 item); difficulty with near vision activities (3 items); difficulty with distance vision activities (3 items); limitations in social functioning due to vision (2 items); role limitations due to vision (2 items); dependency on others due to vision (3 items); mental health symptoms due to vision (4 items); driving difficulties (3 items); limitations with peripheral vision (1 item), limitations with color vision (1 item); and Ocular pain (2 items).
The NEI-VFQ-25 will be measured at every 4-weeks, for Treatment A and every 3-weeks, for Treatment B.
Timepoint [41] 0 0
Baseline and up to 4.5 years
Secondary outcome [42] 0 0
Change from Baseline in symptoms and impacts as measured by PRO-CTCAE, Part 2 - The Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events is a participant-reported outcome measure developed to evaluate symptomatic toxicity in participants on cancer clinical trials. The PRO-CTCAE includes an item library of 124 items representing 80 symptomatic toxicities drawn from the CTCAE.
Timepoint [42] 0 0
Baseline and up to 4.5 years
Secondary outcome [43] 0 0
Number of participants with AE's and SAE's, Part 2 - An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth defect and other situations which involve medical or scientific judgment, and is associated with liver injury and impaired liver function The number of participants experiencing SAE and AEs during, Part 2 of the study will be reported.
Timepoint [43] 0 0
Up to 4.5 years
Secondary outcome [44] 0 0
Number of participants with AE's of special interest (AESI), Part 1 - The AE's of special interest, for GSK2857916 are corneal events, thrombocytopenia and infusion related reactions. The severity of other AESI will be graded utilizing the National Cancer Institute- Common Toxicity Criteria for Adverse Events.
Timepoint [44] 0 0
Up to 4.5 years
Secondary outcome [45] 0 0
Number of participants with AE's of special interest (AESI), Part 2 - The AE's of special interest, for GSK2857916 are corneal events, thrombocytopenia and infusion related reactions. The severity of other AESI will be graded utilizing the National Cancer Institute- Common Toxicity Criteria for Adverse Events.
Timepoint [45] 0 0
Up to 4.5 years
Secondary outcome [46] 0 0
Number of participants with ophthalmic findings on ophthalmic exam, Part 1 - The ophthalmic examinations will be done, by an ophthalmologist (or optometrist), to assess participants who develop corneal events, during the study.
Timepoint [46] 0 0
Up to 4.5 years
Secondary outcome [47] 0 0
Number of participants with ophthalmic findings on ophthalmic exam, Part 2 - The ophthalmic examinations will be done, by an ophthalmologist (or optometrist), to assess participants who develop corneal events, during the study.
Timepoint [47] 0 0
Up to 4.5 years
Secondary outcome [48] 0 0
Change from Baseline in health related quality of life (HRQoL) as measured by European Organization for Research and Treatment of Cancer Quality of life Questionnaire 30-item core module (EORTC QLQ-C30), Part 1 - EORTC QLQ-C30, is a 30-item questionnaire containing both single- and multi-item measures. These include five functional scales (Physical, Role, Cognitive, Emotional, and Social Functioning), three symptom scales (Fatigue, Pain, and Nausea/Vomiting), a Global Health Status/QoL scale, and six single items (Constipation, Diarrhea, Insomnia, Dyspnea, Appetite Loss, and Financial Difficulties). Scores for each scale and single-item measure. A high score for functional scales and for Global Health Status/QoL, represent better functioning ability or HRQoL, whereas a high score for symptom scales and single items represents significant symptomatology.
Timepoint [48] 0 0
Baseline and Up to 4.5 years
Secondary outcome [49] 0 0
Change from Baseline in HRQoL as measured by EORTC, 20-Item Multiple Myeloma Module (QLQ-MY20), Part 1 - QLQ-MY20, module comprises 20 questions that address four myeloma-specific HRQoL domains: Disease Symptoms, Side Effects of Treatment (DSSE), Future Perspective, and Body Image (FPBI). Three of four QLQ-MY20 domains, are multi-item scales: Disease Symptoms (bone aches or pain, back pain, hip pain, arm or shoulder pain, chest pain, and pain increasing with activity); Side effects of treatment (drowsiness, thirst, feeling ill, dry mouth, hair loss, upset by hair loss, tingling hands or feet, restlessness/agitation, acid indigestion/heartburn, and burning or sore eyes); and Future perspective (worry about death and health in future, and thinking about illness). The Body Image scale is single-item scale that addresses physical attractiveness. A high score for DSSE, represents a high level of symptomatology or problems, whereas high score for FPBI, represents better outcomes.
Timepoint [49] 0 0
Baseline and Up to 4.5 years
Secondary outcome [50] 0 0
Change from Baseline in HRQoL as measured by EORTC QLQ-C30, Part 2 - EORTC QLQ-C30, is a 30-item questionnaire containing both single- and multi-item measures. These include five functional scales (Physical, Role, Cognitive, Emotional, and Social Functioning), three symptom scales (Fatigue, Pain, and Nausea/Vomiting), a Global Health Status/QoL scale, and six single items (Constipation, Diarrhea, Insomnia, Dyspnea, Appetite Loss, and Financial Difficulties). A high score for functional scales and for Global Health Status/QoL, represent better functioning ability or HRQoL, whereas a high score for symptom scales and single items represents significant symptomatology.
Timepoint [50] 0 0
Baseline and Up to 4.5 years
Secondary outcome [51] 0 0
Change from Baseline in HRQoL as measured by EORTC, 20-Item MM Module (QLQ-MY20), Part 2 - QLQ-MY20, module comprises 20 questions that address four myeloma-specific HRQoL domains: DSSE, FPBI. Three of four QLQ-MY20 domains, are multi-item scales: Disease Symptoms (bone aches or pain, back pain, hip pain, arm or shoulder pain, chest pain, and pain increasing with activity); Side effects of treatment (drowsiness, thirst, feeling ill, dry mouth, hair loss, upset by hair loss, tingling hands or feet, restlessness/agitation, acid indigestion/heartburn, and burning or sore eyes); and Future perspective (worry about death and health in future, and thinking about illness). The Body Image scale is single-item scale that addresses physical attractiveness. A high score for DSSE, represents a high level of symptomatology or problems, whereas high score for FPBI, represents better outcomes.
Timepoint [51] 0 0
Baseline and Up to 4.5 years

Eligibility
Key inclusion criteria
- Capable of giving signed informed consent.

- Male or female, 18 years or older (at the time consent is obtained).

- Have confirmed diagnosis of Multiple Myeloma (MM) as defined by the IMWG.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 for Arm A and 0
to 2 for Arm B.

- Have undergone stem cell transplant (SCT), or are considered transplant ineligible.

- Have been previously treated with at least 1 prior line of MM therapy, and must have
documented disease progression during or after their most recent therapy according to
the IMWG criteria.

- Must have at least ONE aspect of measurable disease, defined as one the following:
Urine M-protein excretion >=200 milligram (mg)/24 hours, or; Serum M-protein
concentration >=0.5 gram (g)/deciliter (dL) (>=5.0 g/Liter), or; Serum free light
chain (FLC) assay: involved FLC level >=10 mg/dL (>=100 mg/L) and an abnormal serum
FLC ratio (<0.26 or >1.65).

- Participants with a history of autologous SCT, are eligible for study participation
provided the following eligibility criteria are met: Autologous SCT was >100 days
prior to study enrollment; No active bacterial, viral, or fungal infection(s) present;
Participant meets the remainder of the eligibility criteria.

- All prior treatment-related toxicities (defined by National Cancer Institute Common
Toxicity Criteria for Adverse Events [NCI-CTCAE], Version 4.03, 2010) must be <= Grade
1 at the time of enrollment, except for alopecia. Participants with Grade 2 neuropathy
can be enrolled into Len/Dex treatment arm, but not into Bor/Dex treatment arm.

- Adequate organ system functions as defined by the laboratory assessments.

- The contraception's used by female participant's be consistent with local regulations,
regarding methods of contraception for those participating in clinical studies. A
female participant is eligible to participate if she is not pregnant or breastfeeding,
and at least one of the following conditions applies: is not a woman of child bearing
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 120 days after the last dose of study
intervention and agrees not to donate eggs (ova, oocytes) for the purpose of
reproduction during this period. WOCBP must have 2 negative highly sensitive serum
pregnancy tests, as required by local regulations (first within 14 days of Cycle 1 Day
1 and the second one within 24 hours of dosing on Cycle1 Day1) and agree to use
effective contraception during the study and for 120 days after the last dose of study
medication; Additional requirements for pregnancy testing during and after study
intervention (i.e., REMS program for WOCBP taking lenalidomide).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 participant's using contraception should be consistent with local regulations
regarding the methods of contraception for those participating in clinical studies.

- Male participants must agree to refrain from donating sperm and either be abstinent
from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a
long term and persistent basis) and agree to remain abstinent from the time of first
dose of study until 140 days after the last dose of study treatment to allow for
clearance of any altered sperm: 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 when having sexual intercourse with a WOCBP who is not currently pregnant. If the
female partner of the male participant is pregnant at the time of enrollment, or
becomes pregnant during the trial, the male participant must agree to remain abstinent
(if it is consistent with their preferred and usual lifestyle) or use a male condom.
Additional criteria WOCBP participants in Arm A: Due to lenalidomide being a
thalidomide analogue with risk for embryofetal toxicity and prescribed under a
restricted distribution program called the REVLIMID (Lenalidomide) REMS program, WOCBP
participants will be eligible if they commit either to abstain continuously from
heterosexual sexual intercourse or to use two methods of reliable birth control,
beginning 4 weeks prior to initiating treatment with lenalidomide, during therapy,
during dose interruptions and continuing for 120 days following discontinuation of
treatment.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Systemic anti-myeloma therapy (including systemic steroids) within 14 days, or
plasmapheresis within 7 days prior to the first dose of study drug.

- Use of an investigational drug within 14 days or five half-lives (whichever is longer)
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 allogenic stem cell transplant. Note: participants who have undergone syngeneic
transplant will be allowed only if they have no history and no currently active, graft
versus host disease (GvHD) - 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, provided they fulfill criteria.

- 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 active liver or biliary disease (with the exception of Gilbert's syndrome or
asymptomatic gallstones, or otherwise stable chronic liver disease per investigator's
assessment).

- Participants with invasive malignancies other than multiple myeloma are excluded,
unless the second malignancy has been considered medically stable for at least 2
years. The participant must not be receiving active therapy, other than hormonal
therapy for this disease.Note: Participants with curatively treated non-melanoma skin
cancer are allowed without a 2-year restriction.

- Evidence of cardiovascular risk including any of the following: a. Corrected QT (QTc)
interval >=480 millisecond (msec); Evidence of current clinically significant
uncontrolled arrhythmias, including clinically significant ECG abnormalities including
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 3 months of Screening; Class III or
IV heart failure as defined by the New York Heart Association functional
classification system; Uncontrolled hypertension.

- Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to
drugs chemically related to GSK2857916, or any of the components of the study
treatment.

- Pregnant or lactating female.

- Active infection requiring treatment.

- Known 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).

- Current corneal disease except for mild punctuate keratopathy.

- Positive hepatitis C antibody test result or positive hepatitis C RNA test result at
Screening or within 3 months prior to first dose of study treatment. NOTE:
Participants with positive Hepatitis C antibody due to prior resolved disease can be
enrolled, only if a confirmatory negative Hepatitis C ribonucleic acid (RNA) test is
obtained.

- Current corneal disease except for mild punctuate keratopathy.

- Additional Exclusion Criteria for participants Assigned to Treatment A: Participants
unable to tolerate antithrombotic prophylaxis must be excluded; Discontinuation of
prior treatment with lenalidomide due to intolerable AEs.

- Additional Exclusion Criteria for Participants Assigned to Treatment B: Unacceptable
AEs from previous bortezomib treatment; Ongoing Grade 2 or higher peripheral
neuropathy or neuropathic pain from previous bortezomib treatment; Intolerance or
contraindications to anti-viral prophylaxis.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC,WA
Recruitment hospital [1] 0 0
GSK Investigational Site - Fitzroy
Recruitment hospital [2] 0 0
GSK Investigational Site - Melbourne
Recruitment hospital [3] 0 0
GSK Investigational Site - Nedlands
Recruitment postcode(s) [1] 0 0
3065 - Fitzroy
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Indiana
Country [3] 0 0
United States of America
State/province [3] 0 0
Missouri

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Iqvia Pty Ltd
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This study will evaluate the safety and tolerability profile of GSK2857916 when administered
in combination with approved regimens of either Lenalidomide Plus Dexamethasone [Len/Dex (Arm
A)] or Bortezomib Plus Dexamethasone [Bor/Dex (Arm B)] in participants with RRMM, i.e., those
who have relapsed or who are refractory to at least 1 line of approved therapy. Part 1 of the
study is a dose escalation phase to evaluate the safety and tolerability of up to 3 dose
levels and up to 2 dosing schedules of GSK2857916 in combination with the two standard of
care (SoC) regimens. Part 2 will further evaluate the safety and preliminary clinical
activity of GSK2857916 at selected dose levels and dosing schedules in combination with
Len/Dex or Bor/Dex.

Up to a total of 123 evaluable participants will be enrolled in the study with up to 33 Part
1 and up to 90 in Part 2. Participants receiving treatment Arm A, may continue combination
treatment until the occurrence of progressive disease (PD), intolerable adverse events (AEs
), consent withdrawal, or death. The participants receiving treatment Arm B, may continue
combination treatment for a total of up to 8 cycles. After 8 cycles of combination therapy,
the participants will continue treatment with GSK2857916, as a monotherapy until the
occurrence of PD, intolerable AEs, consent withdrawal, or death.
Trial website
https://clinicaltrials.gov/show/NCT03544281
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
US GSK Clinical Trials Call Center
Address 0 0
Country 0 0
Phone 0 0
877-379-3718
Fax 0 0
Email 0 0
GSKClinicalSupportHD@gsk.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03544281