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

Study 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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion 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.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04398745
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

GlaxoSmithKline
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

GSK Clinical Trials
Principal Investigator Affiliation GlaxoSmithKline
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Multiple Myeloma
Arms & Interventions

Arms

Experimental: Part 1: Participants with normal/mild impaired renal function

Participants 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.

Experimental: Part 1: Participants with severe renal impairment

Participants 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.

Experimental: Part 2: Participants with ESRD (not on dialysis)

Participants 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.

Experimental: Part 2: Participants with ESRD (on hemodialysis)

Participants 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.

Interventions

Drug: - Belantamab mafodotin

Belantamab mafodotin will be provided as lyophilized powder which will be available as 100 milligrams per vial (mg/vial) in single-use vial for reconstitution. Lyophilized belantamab mafodotin will reconstituted using water for injection, dilute with normal 0.9 % saline before use.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

GSK Investigational Site, Tucson, Arizona

Status

Recruiting

Address

GSK Investigational Site

Tucson, Arizona, 85724

Site Contact

US GSK Clinical Trials Call Center

GSKClinicalSupportHD@gsk.com

877-379-3718

GSK Investigational Site, Beverly Hills, California

Status

Recruiting

Address

GSK Investigational Site

Beverly Hills, California, 90211

Site Contact

US GSK Clinical Trials Call Center

GSKClinicalSupportHD@gsk.com

877-379-3718

GSK Investigational Site, Jacksonville, Florida

Status

Recruiting

Address

GSK Investigational Site

Jacksonville, Florida, 32224-3899

Site Contact

US GSK Clinical Trials Call Center

GSKClinicalSupportHD@gsk.com

877-379-3718

GSK Investigational Site, Plantation, Florida

Status

Recruiting

Address

GSK Investigational Site

Plantation, Florida, 33322

Site Contact

US GSK Clinical Trials Call Center

GSKClinicalSupportHD@gsk.com

877-379-3718

GSK Investigational Site, Westwood, Kansas

Status

Recruiting

Address

GSK Investigational Site

Westwood, Kansas, 66205

Site Contact

US GSK Clinical Trials Call Center

GSKClinicalSupportHD@gsk.com

877-379-3718

GSK Investigational Site, Stony Brook, New York

Status

Recruiting

Address

GSK Investigational Site

Stony Brook, New York, 11794

Site Contact

US GSK Clinical Trials Call Center

GSKClinicalSupportHD@gsk.com

877-379-3718

GSK Investigational Site, Chapel Hill, North Carolina

Status

Recruiting

Address

GSK Investigational Site

Chapel Hill, North Carolina, 27514

Site Contact

US GSK Clinical Trials Call Center

GSKClinicalSupportHD@gsk.com

877-379-3718

GSK Investigational Site, Monroeville, Pennsylvania

Status

Recruiting

Address

GSK Investigational Site

Monroeville, Pennsylvania, 15146

Site Contact

US GSK Clinical Trials Call Center

GSKClinicalSupportHD@gsk.com

877-379-3718

GSK Investigational Site, The Woodlands, Texas

Status

Recruiting

Address

GSK Investigational Site

The Woodlands, Texas, 77380

Site Contact

US GSK Clinical Trials Call Center

GSKClinicalSupportHD@gsk.com

877-379-3718