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

Overview

About this study

The purpose of this study is to assess the pharmacokinetics (PK), safety, and tolerability of belantamab mafodotin monotherapy in participants with Relapsed/Refractory Multiple Myeloma (RRMM) who have had at least 3 lines of prior treatment and have either normal or impaired renal functions.

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 either are at risk or already have renal dysfunction at initial diagnosis.

 

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and in the study protocol.
  • Male and/or female 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. 
  • Histologically or cytologically confirmed diagnosis of MM, as defined in International Myeloma Working Group (IMWG) criteria [Kumar, 2016] and:
    • has undergone autologous stem cell transplant (SCT); or
    • is considered transplant ineligible; and
    • has failed at least 2 prior lines of anti-myeloma treatments, including an IMiD (e.g., lenalidomide or pomalidomide) and a proteasome inhibitor (e.g., bortezomib, ixazomib or carfilzomib).
  • Has measurable disease with at least one of the following:
    • Serum M-protein ≥ 0.5 g/dL (≥ 5 g/L);
    • Urine M-protein ≥ 200 mg/24 h;
    • Serum FLC assay: Involved FLC level ≥ 10 mg/dL (≥ 100 mg/L) and an abnormal;
    • Serum free light chain ratio (< 0.26 or >1.65).
  • Participants with a history of autologous stem cell transplant are eligible for study participation provided the following eligibility criteria are met:
    • Transplant was > 100 days prior to study enrollment;
    • No active infection(s);
    • Participant meets the remainder of the eligibility criteria outlined in this protocol.
  • Adequate organ system functions as defined by the laboratory assessments listed (please reference protocol)
  • 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%).
  • 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 1 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 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.
    • WOCBP must have a negative highly sensitive serum pregnancy test within 72 hours of dosing on C1D1 and agree to use highly 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.
  • 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 contraception/barrier as detailed below:
        • 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 when having sexual intercourse with a WOCBP (including pregnant females).

Exclusion Criteria:

  • Active plasma cell leukemia at the time of screening. Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes).
  • Participants had a prior allogeneic SCT.
    • NOTE: Participants who have undergone a syngeneic bone marrow transplant will be allowed only if there is no history of, or no currently active graft-versus-host-diseases (GvHD).
  • Prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study drug, or treatment with an investigational agent or approved systemic antimyeloma therapy (including systemic steroids):
    • 14 days or 5 half-lives of receiving the first dose of study drugs, whichever is shorter. The only exception is emergency use of a short course of systemic corticosteroids (equivalent of dexamethasone 40 mg/day for a maximum of 4 days) before treatment.
  • Prior belantamab mafodotin therapy.
  • Participant has received a strong OATP inhibitor within 14 days or 5 half-lives, whichever is shorter, preceding the first dose of study drug (see SRM for more details).
  • 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.
    • NOTE: Stable chronic liver disease (including Gilbert’s syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if participant otherwise meets entry criteria.
  • Participants with previous or concurrent malignancies other than multiple myeloma 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. NOTE: Participants with curatively treated nonmelanoma skin cancer are allowed without a 2-year restriction.
  • Evidence of cardiovascular risk, including any of the following:
    • Evidence of current clinically significant untreated arrhythmias, including clinically significant ECG abnormalities including 2nd degree (Mobitz Type II) or 3rd degree atrioventricular (AV) 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 [NYHA, 1994].
    • 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 (HIV) 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 RNA test result at Screening or within 3 months prior to first dose of study treatment.
    • NOTE: Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled only if a confirmatory negative Hepatitis C RNA test is obtained. Hepatitis RNA testing is required.
  • 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.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

Sikander Ailawadhi, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available
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CLS-20505898

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