Clinical Trials /

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)

NCT03544281

Description:

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.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief 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)
  • Official 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

Clinical Trial IDs

  • ORG STUDY ID: 207497
  • SECONDARY ID: 2017-004689-93
  • NCT ID: NCT03544281

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
GSK2857916Arm A, Part 1, GSK2857916 plus lenalidomide plus dexamethasone
LenalidomideArm A, Part 1, GSK2857916 plus lenalidomide plus dexamethasone
DexamethasoneArm A, Part 1, GSK2857916 plus lenalidomide plus dexamethasone
BortezomibArm B, Part 1, GSK2857916 plus bortezomib plus dexamethasone
GSK2857916Arm A, Part 2, GSK2857916, Expansion

Purpose

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 Arms

NameTypeDescriptionInterventions
Arm A, Part 1, GSK2857916 plus lenalidomide plus dexamethasoneExperimentalModified 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.
  • GSK2857916
  • Lenalidomide
  • Dexamethasone
Arm B, Part 1, GSK2857916 plus bortezomib plus dexamethasoneExperimentalA 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.
  • GSK2857916
  • Dexamethasone
  • Bortezomib
Arm A, Part 2, GSK2857916, ExpansionExperimentalPart 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.
  • Lenalidomide
  • Dexamethasone
  • GSK2857916
Arm B, Part 2, GSK2857916, ExpansionExperimentalPart 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.
  • Dexamethasone
  • Bortezomib
  • GSK2857916

Eligibility Criteria

        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.

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number (percentage[%]) of particpant's with DLTs, Part 1
Time Frame:Up to 4.5 years
Safety Issue:
Description:The number (%) of participant's with DLT's will be reported.

Secondary Outcome Measures

Measure:Maximum plasma concentration (Cmax) for GSK2857916, Part 1, Treatment A
Time Frame: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)
Safety Issue:
Description:Serial blood samples will be collected for pharmacokinetic (PK) analysis.
Measure:Area under the curve (AUC) for GSK2857916, Part 1, Treatment A
Time Frame: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)
Safety Issue:
Description:Serial blood samples will be collected for PK analysis.
Measure:Time to maximum plasma concentration (Tmax) for GSK2857916, Part 1, Treatment A
Time Frame: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)
Safety Issue:
Description:Serial blood samples will be collected for PK analysis.
Measure:Serum half-life (t1/2) for GSK2857916, Part 1, Treatment A
Time Frame: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)
Safety Issue:
Description:Serial blood samples will be collected for PK analysis.
Measure:Cmax for GSK2857916, Part 1, Treatment B
Time Frame: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)
Safety Issue:
Description:Serial blood samples will be collected for PK analysis.
Measure:AUC for GSK2857916, Part 1, Treatment B
Time Frame: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)
Safety Issue:
Description:Serial blood samples, will be collected for PK analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
Measure:Tmax for GSK2857916, Part 1, Treatment B
Time Frame: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)
Safety Issue:
Description:Serial blood samples, will be collected for PK analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
Measure:t1/2 for GSK2857916, Part 1, Treatment B
Time Frame: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)
Safety Issue:
Description:Serial blood samples, will be collected for PK analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
Measure:Cmax for GSK2857916, Part 2, Treatment A
Time Frame: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)
Safety Issue:
Description:Serial blood samples will be collected for PK analysis.
Measure:AUC for GSK2857916, Part 2, Treatment A
Time Frame: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)
Safety Issue:
Description:Serial blood samples will be collected for PK analysis.
Measure:Tmax for GSK2857916, Part 2, Treatment A
Time Frame: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)
Safety Issue:
Description:Serial blood samples will be collected for PK analysis.
Measure:t1/2 for GSK2857916, Part 2, Treatment A
Time Frame: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)
Safety Issue:
Description:Serial blood samples will be collected for PK analysis.
Measure:Cmax for GSK2857916, Part 2, Treatment B
Time Frame: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)
Safety Issue:
Description:Serial blood samples, will be collected for PK analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
Measure:AUC for GSK2857916, Part 2, Treatment B
Time Frame: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)
Safety Issue:
Description:Serial blood samples, will be collected for PK analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
Measure:Tmax for GSK2857916, Part 2, Treatment B
Time Frame: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)
Safety Issue:
Description:Serial blood samples, will be collected for PK analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
Measure:t1/2 for GSK2857916, Part 2, Treatment B
Time Frame: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)
Safety Issue:
Description:Serial blood samples, will be collected for PK analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
Measure:Cmax for Lenalidomide, Part 1, Treatment A
Time Frame:At pre-dose, and 0.5, 1, 2, and 4 hour post dose on Day 1 of Cycle 1 (each cycle is 28 days)
Safety Issue:
Description:Serial blood samples will be collected for PK analysis.
Measure:AUC for Lenalidomide, Part 1, Treatment A
Time Frame:At pre-dose, and 0.5, 1, 2, and 4 hour post dose on Day 1 of Cycle 1 (each cycle is 28 days)
Safety Issue:
Description:Serial blood samples will be collected for PK analysis.
Measure:Tmax for Lenalidomide, Part 1, Treatment A
Time Frame:At pre-dose, and 0.5, 1, 2, and 4 hour post dose on Day 1 of Cycle 1 (each cycle is 28 days)
Safety Issue:
Description:Serial blood samples will be collected for PK analysis.
Measure:t1/2 for Lenalidomide, Part 1, Treatment A
Time Frame:At pre-dose, and 0.5, 1, 2, and 4 hour post dose on Day 1 of Cycle 1 (each cycle is 28 days)
Safety Issue:
Description:Serial blood samples will be collected for PK analysis.
Measure:Cmax for Bortezomib, Part 1, Treatment B
Time Frame: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)
Safety Issue:
Description:Serial blood samples, will be collected for PK analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
Measure:AUC for Bortezomib, Part 1, Treatment B
Time Frame: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)
Safety Issue:
Description:Serial blood samples, will be collected for PK analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
Measure:Tmax for Bortezomib, Part 1, Treatment B
Time Frame: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)
Safety Issue:
Description:Serial blood samples, will be collected for PK analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
Measure:t1/2 for Bortezomib, Part 1, Treatment B
Time Frame: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)
Safety Issue:
Description:Serial blood samples, will be collected for PK analysis. The sampling beyond Cycle 12, was conducted at pre-dose every 6th Cycle.
Measure:Cmax for Lenalidomide, Part 2, Treatment A
Time Frame: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)
Safety Issue:
Description:Serial blood samples will be collected for PK analysis.
Measure:AUC for Lenalidomide, Part 2, Treatment A
Time Frame: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)
Safety Issue:
Description:Serial blood samples will be collected for PK analysis.
Measure:Tmax for Lenalidomide, Part 2, Treatment A
Time Frame: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)
Safety Issue:
Description:Serial blood samples will be collected for PK analysis.
Measure:t1/2 for Lenalidomide, Part 2, Treatment A
Time Frame: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)
Safety Issue:
Description:Serial blood samples will be collected for PK analysis.
Measure:Cmax for Lenalidomide, Part 2, Treatment B
Time Frame: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)
Safety Issue:
Description:Serial blood samples will be collected for PK analysis.
Measure:AUC for Lenalidomide, Part 2, Treatment B
Time Frame: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)
Safety Issue:
Description:Serial blood samples will be collected for PK analysis.
Measure:Tmax for Lenalidomide, Part 2, Treatment B
Time Frame: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)
Safety Issue:
Description:Serial blood samples will be collected for PK analysis.
Measure:t1/2 for Lenalidomide, Part 2, Treatment B
Time Frame: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)
Safety Issue:
Description:Serial blood samples will be collected for PK analysis.
Measure:Number of participants with anti-drug antibodies (ADAs) against GSK2857916, Part 1, Treatment A
Time Frame:Pre-dose on Day 1 of Cycle 1, 2, 3, 6, 9, 12 (Each cycle is of 28 days)
Safety Issue:
Description: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.
Measure:Number of participants with ADAs, against GSK2857916, Part 1 treatment B
Time Frame:Pre-dose on Day 1 of Cycle 1, 2, 3, 6, 9, 12 (Each cycle is of 21 days)
Safety Issue:
Description: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.
Measure:Number of participants with ADAs, against GSK2857916, Part 2 Treatment A
Time Frame:Pre-dose on Day 1 of Cycle 1, 2, 3, 6, 9, 12 (Each cycle is of 28 days)
Safety Issue:
Description: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.
Measure:Number of participants with ADAs, against GSK2857916, Part 2, Treatment B
Time Frame:Pre-dose on Day 1 of Cycle 1, 2, 3, 6, 9, 12 (Each cycle is of 21 days)
Safety Issue:
Description: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.
Measure:Change from Baseline in symptoms and impacts as measured by Ocular Surface Disease Index (OSDI), Part 1
Time Frame:Baseline and up to 4.5 years
Safety Issue:
Description: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.
Measure:Change from Baseline in symptoms and impacts as measured by the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25), Part 1
Time Frame:Baseline and up to 4.5 years
Safety Issue:
Description: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.
Measure: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
Time Frame:Baseline and up to 4.5 years
Safety Issue:
Description: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.
Measure:Change from Baseline in symptoms and impacts as measured by OSDI, Part 2
Time Frame:Baseline and up to 4.5 years
Safety Issue:
Description: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.
Measure:Change from Baseline in symptoms and impacts as measured by NEI-VFQ-25, Part 2
Time Frame:Baseline and up to 4.5 years
Safety Issue:
Description: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.
Measure:Change from Baseline in symptoms and impacts as measured by PRO-CTCAE, Part 2
Time Frame:Baseline and up to 4.5 years
Safety Issue:
Description: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.
Measure:Number of participants with AE's and SAE's, Part 2
Time Frame:Up to 4.5 years
Safety Issue:
Description: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.
Measure:Number of participants with AE's of special interest (AESI), Part 1
Time Frame:Up to 4.5 years
Safety Issue:
Description: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.
Measure:Number of participants with AE's of special interest (AESI), Part 2
Time Frame:Up to 4.5 years
Safety Issue:
Description: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.
Measure:Number of participants with ophthalmic findings on ophthalmic exam, Part 1
Time Frame:Up to 4.5 years
Safety Issue:
Description:The ophthalmic examinations will be done, by an ophthalmologist (or optometrist), to assess participants who develop corneal events, during the study.
Measure:Number of participants with ophthalmic findings on ophthalmic exam, Part 2
Time Frame:Up to 4.5 years
Safety Issue:
Description:The ophthalmic examinations will be done, by an ophthalmologist (or optometrist), to assess participants who develop corneal events, during the study.
Measure: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
Time Frame:Baseline and Up to 4.5 years
Safety Issue:
Description: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.
Measure:Change from Baseline in HRQoL as measured by EORTC, 20-Item Multiple Myeloma Module (QLQ-MY20), Part 1
Time Frame:Baseline and Up to 4.5 years
Safety Issue:
Description: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.
Measure:Change from Baseline in HRQoL as measured by EORTC QLQ-C30, Part 2
Time Frame:Baseline and Up to 4.5 years
Safety Issue:
Description: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.
Measure:Change from Baseline in HRQoL as measured by EORTC, 20-Item MM Module (QLQ-MY20), Part 2
Time Frame:Baseline and Up to 4.5 years
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:GlaxoSmithKline

Trial Keywords

  • Relapsed / Refractory Multiple Myeloma
  • Dose escalation
  • Antibody-Drug Conjugate
  • Dose expansion

Last Updated

September 10, 2019