A Study of Belantamab Mafodotin (GSK2857916) in Multiple Myeloma Participants
a study on Multiple Myeloma
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.
A Phase I Study to Evaluate the Pharmacokinetics and Safety of Belantamab Mafodotin Monotherapy in Participants With Relapsed and/or Refractory Multiple Myeloma (RRMM) Who Have Normal and Varying Degrees of Impaired Renal Function (DREAMM 12)
Multiple Myeloma DREAMM 12 End-stage renal disease Normal renal function Renal impairment Relapsed and/or refractory multiple myeloma Belantamab mafodotin Neoplasms, Plasma Cell Renal Insufficiency
You can join if…
Open to people ages 18 years and up
- 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 109 per liter (/L); Hemoglobin >=7.0 g/dL or 4.9 millimoles per liter (mmol/L); Platelets >= 50 x 109/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/1.73m2); Group 2: severe 15-29 mL/min/1.73 m2; Group 3: ESRD (not on dialysis) <15 mL/min/1.73 m2; Group 4: ESRD (on dialysis) <15 mL/min/1.73 m2; 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).
You CAN'T join if...
- 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.
- GSK Investigational Site
accepting new patients
Beverly Hills California 90211 United States
- GSK Investigational Site
accepting new patients
Tucson Arizona 85724 United States
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