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

Study 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.

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 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.

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.

NCT04398680
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 hepatic function

Participants 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.

Experimental: Part 1: Participants with moderate hepatic impairment

Participants 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.

Experimental: Part 2: Participants with severe hepatic impairment

Participants 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.

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 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, Chicago, Illinois

Status

Recruiting

Address

GSK Investigational Site

Chicago, Illinois, 60611

Site Contact

US GSK Clinical Trials Call Center

GSKClinicalSupportHD@gsk.com

877-379-3718

GSK Investigational Site, Wichita, Kansas

Status

Recruiting

Address

GSK Investigational Site

Wichita, Kansas, 67214

Site Contact

US GSK Clinical Trials Call Center

GSKClinicalSupportHD@gsk.com

877-379-3718

GSK Investigational Site, Baltimore, Maryland

Status

Recruiting

Address

GSK Investigational Site

Baltimore, Maryland, 21201-1595

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, Milwaukee, Wisconsin

Status

Recruiting

Address

GSK Investigational Site

Milwaukee, Wisconsin, 53233

Site Contact

US GSK Clinical Trials Call Center

GSKClinicalSupportHD@gsk.com

877-379-3718