Clinical Trials /

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

NCT04398680

Description:

Belantamab mafodotin (GSK2857916) is an antibody-drug conjugate (ADC) containing humanized anti- B-cell maturation antigen (BCMA) monoclonal antibody (mAb). Impaired hepatic function may alter the pharmacokinetics (PK) and pharmacodynamics (PD) of belantamab mafodotin, a drug that is primarily hepatically eliminated and hence may require adjustments in dosing regimens as compared to patients who have normal hepatic function. The purpose of this study is assess the PK, safety, and tolerability of belantamab mafodotin monotherapy in Relapsed/Refractory Multiple Myeloma (RRMM) participants with impaired hepatic function and in matched RRMM participants with normal hepatic function. The study will consist of two parts: Part 1 will include participants with normal hepatic function and moderate hepatic impairment and Part 2 will include participants with severe hepatic impairment. Participants will be administered GSK2857916 at a dose of 2.5 milligram per kilogram (mg/kg) intravenously in Part 1 and in Part 2, dose will depend on the evaluation of pharmacokinetic and safety data of Part 1. However, dose in Part 2 will not exceed 2.5 mg/kg. 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:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of Belantamab Mafodotin (GSK2857916) in Multiple Myeloma Participants With Normal and Impaired Hepatic Function
  • Official Title: A Phase I Study to Evaluate the Pharmacokinetics and Safety of Belantamab Mafodotin Monotherapy in Participants With Relapsed or Refractory Multiple Myeloma Who Have Normal and Varying Degrees of Impaired Hepatic Function (DREAMM 13)

Clinical Trial IDs

  • ORG STUDY ID: 209627
  • NCT ID: NCT04398680

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
Belantamab mafodotinPart 1: Participants with moderate hepatic impairment

Purpose

Belantamab mafodotin (GSK2857916) is an antibody-drug conjugate (ADC) containing humanized anti- B-cell maturation antigen (BCMA) monoclonal antibody (mAb). Impaired hepatic function may alter the pharmacokinetics (PK) and pharmacodynamics (PD) of belantamab mafodotin, a drug that is primarily hepatically eliminated and hence may require adjustments in dosing regimens as compared to patients who have normal hepatic function. The purpose of this study is assess the PK, safety, and tolerability of belantamab mafodotin monotherapy in Relapsed/Refractory Multiple Myeloma (RRMM) participants with impaired hepatic function and in matched RRMM participants with normal hepatic function. The study will consist of two parts: Part 1 will include participants with normal hepatic function and moderate hepatic impairment and Part 2 will include participants with severe hepatic impairment. Participants will be administered GSK2857916 at a dose of 2.5 milligram per kilogram (mg/kg) intravenously in Part 1 and in Part 2, dose will depend on the evaluation of pharmacokinetic and safety data of Part 1. However, dose in Part 2 will not exceed 2.5 mg/kg. 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 hepatic functionExperimentalParticipants with normal hepatic function (Serum bilirubin and Aspartate aminotransferase [AST] <= Upper limit of normal [ULN]) will be administered with Belantamab mafodotin 2.5 mg/kg intravenous infusion over 30 minutes 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 moderate hepatic impairmentExperimentalParticipants with moderate hepatic impairment (Serum bilirubin >1.5 - 3 × ULN and any AST) will be administered with Belantamab mafodotin 2.5 mg/kg intravenous infusion over 30 minutes 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 severe hepatic impairmentExperimentalParticipants with severe hepatic impairment (Serum bilirubin >3 × ULN and any AST) will be administered with Belantamab mafodotin either 2.5 mg/kg or 1.9 mg/kg (or other lower adjusted dose) intravenous infusion over 30 minutes 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 must be 18 years of age or older, at the time of signing the
             informed consent.

          -  Eastern Cooperative Oncology Group performance status 0-2.

          -  Participants with histologically or cytologically confirmed diagnosis of multiple
             myeloma, 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 milligram per 24 hours (mg/24 hr); and Serum free light chain assay:
             Involved free light chain level >=10 milligrams per deciliter (mg/dL) (>=100
             milligrams per liter [mg/L]) and an abnormal serum free light chain 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/liter (L); Hemoglobin >=8.0 g/dL (or 4.9 millimoles per
             liter); Platelets >= 75 x 10^9/L; Serum bilirubin and aspartate aminotransferase:
             Group 1 (normal) serum bilirubin and aspartate aminotransferase <=upper limit of
             normal (ULN); Group 2 (moderate) serum bilirubin >1.5-3 x ULN and any aspartate
             aminotransferase; alanine aminotransferase <=5 x ULN; Estimated glomerular filtration
             rate >=30 milliliter per minute per 1.73 meter square (mL/min/m^2); and left
             ventricular ejection fraction by echocardiograms >=45%.

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

          -  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 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 9 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 effective
             contraception during the study and for 9 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, Plus, any of the following: 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).

          -  Participants with a history of Hepatitis B virus and/or Hepatitis C virus exposure are
             eligible under specific conditions.

        Exclusion Criteria:

          -  Active plasma cell leukemia at the time of screening. Symptomatic amyloidosis, active
             polyneuropathy, organomegaly, endocrinopathy, myeloma protein and skin changes,
             Waldenstroem Macroglobulinemia.

          -  Participants had a prior allogeneic SCT.

          -  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 or prior belantamab mafodotin. The only exception
             is emergency use of a short course of systemic corticosteroids (equivalent of
             dexamethasone 40 milligrams per day [mg/day] for a maximum of 4 days) before
             treatment.

          -  Participant has received a strong Organic-anion transporting polypeptide (OATP)
             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.

          -  Any serious and/or unstable pre-existing medical, psychiatric disorder or other
             conditions (including lab abnormalities except hepatic 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
             sudden onset of, or clinically relevant changes in: ascites, encephalopathy,
             coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, in
             the last 14 days prior to the first dose. Participants with cirrhosis are excluded.
             Participants with focal lesions due to other causes than underlying multiple myeloma
             are excluded.

          -  Participants with acute hepatitis B virus infection are excluded. Participants with
             chronic hepatitis B infection (active or core antibody positive) are only allowed if
             the criteria from Organ System Function are fulfilled and if appropriate antiviral
             treatment per local guidance (e.g. tenofovir or entecavir) is started before starting
             belantamab mafodotin, continues through to completion of belantamab mafodotin therapy
             and is not to be stopped unless advised by local hepatology or virology.

          -  Participants with evidence of hepatitis C virus infection, defined as positive
             hepatitis C virus - ribonucleic acid test result at screening or within 3 months prior
             to first dose of study treatment, are excluded unless successfully treated prior to
             enrollment with a curative 8-12 week antiviral treatment course and the hepatitis C
             virus - ribonucleic acid negative status has been confirmed after at least 4 weeks
             washout of the antiviral treatment.

          -  Participants with Gilbert's syndrome.

          -  Participants with previous or concurrent malignancies other than multiple myeloma,
             except: The disease must be considered medically stable for at least 2 years; or 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 including second degree (Mobitz Type II) or third
             degree atrioventricular 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; History of severe
             non-ischemic cardiomyopathy; and 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.

          -  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: Change from Baseline in Vital Signs- Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) (millimeters 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: 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: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
Time Frame:Up to 4 years
Safety Issue:
Description:An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment.
Measure:Part 1: Number of participants with toxicity grading for hematology parameters
Time Frame:Up to 4 years
Safety Issue:
Description:Blood samples will be collected from participants for the analysis of hematology parameters: platelet count, red blood cell count, white blood cell count, reticulocyte count, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, neutrophils, lymphocytes, monocytes, eosinophils and basophils.
Measure:Part 1: Number of participants with toxicity grading for clinical chemistry parameters
Time Frame:Up to 4 years
Safety Issue:
Description:Blood samples will be collected from participants for the analysis of clinical chemistry parameters: blood urea nitrogen, potassium, aspartate aminotransferase, total and direct bilirubin, creatinine, chloride, alanine aminotransferase, uric acid, glucose (non-fasting), total bicarbonate, gamma glutamyl transferase, albumin, sodium, calcium, alkaline phosphatase, total protein, magnesium, phosphorous, creatine kinase, lactate dehydrogenase, estimated glomerular filtration rate and international normalization ratio and prothrombin time.
Measure:Part 1: Number of participants with toxicity grading for urine parameters
Time Frame:Up to 4 years
Safety Issue:
Description:Urine samples will be collected from participants for the analysis of urinalysis parameters: urine protein and albumin/creatinine ratio.
Measure:Part 1: Number of participants with abnormal electrocardiogram findings
Time Frame:Up to 4 years
Safety Issue:
Description:Twelve lead electrocardiograms will be obtained using an automated electrocardiogram machine that calculates heart rate and measures PR, QRS, QT and corrected QT intervals according to Fridericia's formula.
Measure:Part 1: 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.
Measure:Part 2: Change from Baseline in Vital Signs- DBP and SBP (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 2: Change from Baseline in Vital Signs- 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 2: Number of participants with AEs and SAEs
Time Frame:Up to 4 years
Safety Issue:
Description:An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment.
Measure:Part 2: Number of participants with toxicity grading for hematology parameters
Time Frame:Up to 4 years
Safety Issue:
Description:Blood samples will be collected from participants for the analysis of hematology parameters: platelet count, red blood cell count, white blood cell count, reticulocyte count, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, neutrophils, lymphocytes, monocytes, eosinophils, and basophils.
Measure:Part 2: Number of participants with toxicity grading for clinical chemistry parameters
Time Frame:Up to 4 years
Safety Issue:
Description:Blood samples will be collected from participants for the analysis of clinical chemistry parameters: blood urea nitrogen, potassium, aspartate aminotransferase, total and direct bilirubin, creatinine, chloride, alanine aminotransferase, uric acid, glucose (non-fasting), total bicarbonate, gamma glutamyl transferase, albumin, sodium, calcium, alkaline phosphatase, total protein, magnesium, phosphorous, creatine kinase, lactate dehydrogenase and estimated glomerular filtration rate, international normalization ratio and prothrombin time.
Measure:Part 2: Number of participants with toxicity grading for urine parameters
Time Frame:Up to 4 years
Safety Issue:
Description:Urine samples will be collected from participants for the analysis of urinalysis parameters: urine protein and albumin/creatinine ratio.
Measure:Part 2: Number of participants with abnormal electrocardiogram findings
Time Frame:Up to 4 years
Safety Issue:
Description:Twelve lead electrocardiograms will be obtained using an automated electrocardiogram machine that calculates heart rate and measures PR, QRS, QT and corrected QT intervals according to Fridericia's formula.
Measure: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:Not yet recruiting
Lead Sponsor:GlaxoSmithKline

Trial Keywords

  • DREAMM 13
  • Belantamab mafodotin monotherapy
  • Hepatic impairment
  • Normal hepatic function
  • Relapsed or refractory multiple myeloma

Last Updated

October 6, 2020