Clinical Trials /

A Study of Belantamab Mafodotin (GSK2857916) in Multiple Myeloma Participants With Normal and Varying Degree of Impaired Renal Function

NCT04398745

Description:

Belantamab mafodotin (GSK2857916) is an antibody-drug conjugate (ADC) containing humanized anti- B-cell maturation antigen (BCMA) monoclonal antibody (mAb). Renal impairment is a major complication of multiple myeloma (MM) and majority of MM participants are either at risk or already have renal dysfunction at initial diagnosis. The purpose of this study is to assess the pharmacokinetics (PK), safety, and tolerability of belantamab mafodotin monotherapy in participants with RRMM, who have had at least 3 lines of prior treatment and have either normal or impaired renal functions. The study will consist of two parts: part 1 will include participants with normal/mildly impaired renal function and severe renal impairment and part 2 will include participants with end-stage renal disease (ESRD), where participants are either not undergoing or require hemodialysis. Participants will be administered GSK2857916 at a dose of 2.5 milligram per kilogram (mg/kg) intravenously once in three weeks (Q3W) dosing in Part 1. Based on the Part 1 Safety/Pharmacokinetic (PK) data, Part 2 participants will be administered the dose of either 2.5 mg/kg or 1.9 mg/kg (or other adjusted dose). Participants will be treated with GSK2857916 monotherapy until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, or end of study, whichever occurs first. This study will include a screening phase, treatment phase, and follow- up phase. The total duration of the study is approximately up to 48 months.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of Belantamab Mafodotin (GSK2857916) in Multiple Myeloma Participants With Normal and Varying Degree of Impaired Renal Function
  • Official Title: A Phase I Study to Evaluate the Pharmacokinetics and Safety of Belantamab Mafodotin Monotherapy in Participants With Relapsed and/or Refractory Multiple Myeloma (RRMM) Who Have Normal and Varying Degrees of Impaired Renal Function (DREAMM 12)

Clinical Trial IDs

  • ORG STUDY ID: 209626
  • NCT ID: NCT04398745

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
Belantamab mafodotinPart 1: Participants with normal/mild impaired renal function

Purpose

Belantamab mafodotin (GSK2857916) is an antibody-drug conjugate (ADC) containing humanized anti- B-cell maturation antigen (BCMA) monoclonal antibody (mAb). Renal impairment is a major complication of multiple myeloma (MM) and majority of MM participants are either at risk or already have renal dysfunction at initial diagnosis. The purpose of this study is to assess the pharmacokinetics (PK), safety, and tolerability of belantamab mafodotin monotherapy in participants with RRMM, who have had at least 3 lines of prior treatment and have either normal or impaired renal functions. The study will consist of two parts: part 1 will include participants with normal/mildly impaired renal function and severe renal impairment and part 2 will include participants with end-stage renal disease (ESRD), where participants are either not undergoing or require hemodialysis. Participants will be administered GSK2857916 at a dose of 2.5 milligram per kilogram (mg/kg) intravenously once in three weeks (Q3W) dosing in Part 1. Based on the Part 1 Safety/Pharmacokinetic (PK) data, Part 2 participants will be administered the dose of either 2.5 mg/kg or 1.9 mg/kg (or other adjusted dose). Participants will be treated with GSK2857916 monotherapy until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, or end of study, whichever occurs first. This study will include a screening phase, treatment phase, and follow- up phase. The total duration of the study is approximately up to 48 months.

Trial Arms

NameTypeDescriptionInterventions
Part 1: Participants with normal/mild impaired renal functionExperimentalParticipants with normal or mildly impaired renal function (Normal: estimated glomerular filtration rate [eGFR]: >=90 milliliter per minute per 1.73 meter square [mL/min/1.73 m^2]; Mild impairment: eGFR: 60-89 mL/min/1.73 m^2) will be administered with belantamab mafodotin 2.5 mg/kg as an intravenous infusion over 30 minutes Q3W on Day 1 of every 21- day cycle until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, or end of study, whichever occurs first.
  • Belantamab mafodotin
Part 1: Participants with severe renal impairmentExperimentalParticipants with severely impaired renal function (eGFR: 15-29 mL/min/1.73 m^2) will be administered with belantamab mafodotin 2.5 mg/kg as an intravenous infusion over 30 minutes Q3W on Day 1 of every 21- day cycle until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, or end of study, whichever occurs first.
  • Belantamab mafodotin
Part 2: Participants with ESRD (not on dialysis)ExperimentalParticipants with ESRD (eGFR: <15 mL/min/1.73 m^2) not on dialysis will be administered with belantamab mafodotin either 2.5 mg/kg or 1.9 mg/kg (or other adjusted dose) as an intravenous infusion over 30 minutes Q3W on Day 1 of every 21- day cycle until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, or end of study, whichever occurs first. In Part 2, dose will be decided after evaluation of pharmacokinetic and safety data of Part 1.
  • Belantamab mafodotin
Part 2: Participants with ESRD (on hemodialysis)ExperimentalParticipants with ESRD (eGFR: <15 mL/min/1.73 m^2) on hemodialysis will be administered with belantamab mafodotin either 2.5 mg/kg or 1.9 mg/kg (or other adjusted dose) as an intravenous infusion over 30 minutes Q3W on Day 1 of every 21-day cycle until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, or end of study, whichever occurs first. In Part 2, dose will be decided after evaluation of pharmacokinetic and safety data of Part 1.
  • Belantamab mafodotin

Eligibility Criteria

        Inclusion Criteria:

          -  Participants are capable of giving signed informed consent which includes compliance
             with the requirements and restrictions listed in the Informed Consent Form.

          -  Male and/or female participants must be 18 years of age or older, at the time of
             signing the informed consent.

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

          -  Participants with histologically or cytologically confirmed diagnosis of MM, as
             defined in International Myeloma Working Group criteria: 1. Has undergone autologous
             stem cell transplant (SCT) or is considered transplant-ineligible; 2. Has failed at
             least 2 prior lines of anti-myeloma treatments, including an immunomodulatory drugs
             (example [e.g.], lenalidomide or pomalidomide) and a proteasome inhibitor (e.g.,
             bortezomib, ixazomib or carfilzomib).

          -  Participants 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 milligrams (mg) per 24 hours (mg/24 h); and Serum free light chain
             (FLC) assay: Involved FLC level >=10 milligrams per deciliter (mg/dL) (>=100
             milligrams per liter [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: 1. Transplant was >100 days prior
             to study enrollment, 2. No active infection(s), and 3. Participant meets the remainder
             of the eligibility criteria outlined in this protocol.

          -  Participants with adequate organ system functions as defined follows: Absolute
             neutrophil count >=1.0 x 10^9 per liter (/L); Hemoglobin >=7.0 g/dL or 4.9 millimoles
             per liter (mmol/L); Platelets >= 50 x 10^9/L; Total bilirubin <=1.5 x Upper limit of
             normal (ULN) (Isolated bilirubin >=1.5 x ULN is acceptable if bilirubin is
             fractionated and direct bilirubin <35 percent [%]); Alanine aminotransferase <=2.5 x
             ULN; eGFR, Group 1: normal/ mild impairment >=60milliliter per minute per 1.73 meter
             square (mL/min/1.73m^2); Group 2: severe 15-29 mL/min/1.73 m^2; Group 3: ESRD (not on
             dialysis) <15 mL/min/1.73 m^2; Group 4: ESRD (on dialysis) <15 mL/min/1.73 m^2; and
             left ventricular ejection fraction by echocardiograms >=40%.

          -  Main additional inclusion criteria in Group 1 (matched control participants): Matched
             to at least one severely renal impaired participant by Baseline body weight (+/-20%)
             and Baseline albumin levels (+/-10%).

          -  Female participants: Contraceptive use by 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 at least one of the following conditions applies: Is 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 4 months 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
             within 72 hours of dosing on Cycle 1 Day 1 and agree to use highly effective
             contraception during the study and for 4 months after the last dose of study
             medication. 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 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
             from the time of first dose of study until 6 months after the last dose of study
             treatment to allow for clearance of any altered sperm: 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; OR must agree to use a male condom even if they have undergone a successful
             vasectomy 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 (including pregnant females).

        Exclusion Criteria:

          -  Participants with active plasma cell leukemia at the time of screening. Symptomatic
             amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy,
             myeloma protein and skin changes), Waldenstroem Macroglobulinemia

          -  Participants had a prior allogeneic stem cell transplant.

          -  Participant has received an investigational drug within 14 days or 5 half-lives
             whichever is shorter, preceding the first dose of study drug. This includes prior
             treatment with a monoclonal antibody. The only exception is emergency use of a short
             course of systemic corticosteroids (equivalent to, or less than: dexamethasone 40
             milligrams per day [mg/day] for a maximum of 4 days) before treatment.

          -  Prior belantamab mafodotin therapy.

          -  Participant has received a strong Organic-anion transporting polypeptide inhibitor
             within 14 days or 5 half-lives, whichever is shorter, preceding the first dose of
             study drug.

          -  Systemic active infection requiring treatment.

          -  Any unresolved toxicity >=Grade 2 from previous treatment except for alopecia, or
             peripheral neuropathy up to Grade 2.

          -  Plasmapheresis within 7 days prior to the first dose of study drug. Screening
             laboratory values must be performed after last plasmapheresis.

          -  Any major surgery within the last 4 weeks prior to Day 1 of Screening.

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

          -  Evidence of active mucosal or internal bleeding.

          -  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.

          -  Participants with previous or concurrent malignancies other than MM are excluded,
             unless the prior 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.

          -  Evidence of cardiovascular risk including any of the following: Evidence of current
             clinically significant untreated arrhythmias, including clinically significant
             electrocardiogram abnormalities such as second degree (Mobitz Type II) or third degree
             atrioventricular block; History of myocardial infarction (within prior 18 months),
             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 belantamab mafodotin, or any of the components of the
             study treatment.

          -  Known human immunodeficiency virus infection.

          -  Presence of hepatitis B surface antigen (HbsAg) or hepatitis B core antibody
             (anti-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
             test result at Screening or within 3 months prior to first dose of study treatment.

          -  Participants with renal impairment due to hepatic disease (hepatorenal syndrome).

          -  Current corneal epithelial disease except for mild punctuate keratopathy.

          -  Participant is a woman who is pregnant or breastfeeding.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part 1: Maximum observed plasma concentration (Cmax) of GSK2857916
Time Frame:Cycle1:predose,end infusion (EOI), 2, 4, 8, 24 hours(h) postdose on Days(D) 4,8,15 & 22(Cycle2 Day1 predose); Cycle2:predose, EOI & 24 h postdose; Cycle3:predose, EOI, 2, 4, 8, 24 h postdose on D 4, 8, 15 & 22(Cycle4 Day1 predose) (each cycle is 21 days)
Safety Issue:
Description:Blood samples will be collected at indicated time points for pharmacokinetic analysis.

Secondary Outcome Measures

Measure:Part 1 and Part 2: Change from Baseline in Vital Signs- Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) (millimeter of mercury [mmHg])
Time Frame:Baseline and up to 4 years
Safety Issue:
Description:Vital signs will be measured after resting for at least 5 minutes.
Measure:Part 1 and Part 2: Change from Baseline in Vital Sign- Heart rate (beats per minute)
Time Frame:Baseline and up to 4 years
Safety Issue:
Description:Vital signs will be measured after resting for at least 5 minutes.
Measure:Part 1 and Part 2: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
Time Frame:Up to 4 years
Safety Issue:
Description:AEs and SAEs will be collected at specified time points.
Measure:Part 1 and Part 2: Number of participants with toxicity grading for hematology and clinical chemistry parameters
Time Frame:Up to 4 years
Safety Issue:
Description:Blood samples will be collected from participants for the analysis of toxicity grading for hematology, and clinical chemistry parameters
Measure:Part 1 and Part 2: Number of participants with toxicity grading for urinalysis parameters
Time Frame:Up to 4 years
Safety Issue:
Description:Urine samples will be collected from participants for the analysis of toxicity grading for urinalysis parameters.
Measure:Part 1 and Part 2: Number of participants with abnormal physical examination parameters
Time Frame:Up to 4 years
Safety Issue:
Description:Physical examination parameters will include assessments of the head, eyes, ears, nose, throat, skin, thyroid, lungs, cardiovascular, abdomen (liver and spleen), lymph nodes, and extremities.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:GlaxoSmithKline

Trial Keywords

  • DREAMM 12
  • End-stage renal disease
  • Normal renal function
  • Renal impairment
  • Relapsed and/or refractory multiple myeloma
  • Belantamab mafodotin

Last Updated

October 20, 2020