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

• Status: Recruiting
• Trial end date: 2024-05-06
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to assess the pharmacokinetics (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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: GlaxoSmithKline

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 greater than or equal to (>=)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 times 10^9/liter (L); Hemoglobin >=8.0 g/dL (or 4.9 millimoles per liter); Platelets >= 75 times 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 times ULN and any aspartate aminotransferase; alanine aminotransferase <=5 ULN; Estimated glomerular filtration rate >=60 milliliter per minute per 1.73 meter square (mL/min/m^2); Urine dipstick for protein or Albumin/creatinine ratio (from spot urine) negative/trace (if >=1+ only eligible if confirmed <=500 mg/g (56 mg/mmol) by albumin/creatinine ratio (spot urine from first void; and left ventricular ejection fraction by echocardiograms >=45 percent (%).

• 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).

• 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.

• 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.

• Prior belantamab mafodotin therapy

• Systemic active infection requiring treatment

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

• 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.

• 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.

• 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 human immunodeficiency virus infection.

• Current corneal epithelial disease except for mild punctuate keratopathy.

• Participant is a woman who is pregnant or breastfeeding.