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.
In Republic of Korea, participants must be 19 years of
age or older at the time of signing 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 drug
(example [e.g.], lenalidomide or pomalidomide) and a proteasome inhibitor (e.g.,
bortezomib, ixazomib or carfilzomib). In Republic of Korea, participants should also
have relapsed or refractory disease after treatment with an anti-CD38 antibody, if
accessible to patients, or other suitable local standard of care.
- - Participants have 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; iGFR, Group 1: normal/ mildly impaired >=60milliliter per minute (mL/min); Group
2: severe 15-29 mL/min; Group 3: ESRD (not on dialysis) <15 mL/min; Group 4: ESRD (on
dialysis) <15 mL/min; 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.
. 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).
- - 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.
(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 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. (Participants with curatively treated non-melanoma 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
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
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, unless the participant can meet all of
the following criteria: Established anti-retroviral therapy (ART) for at least 4 weeks
and HIV viral load <400 copies/mL prior to first dose; CD4+ T-cell (CD4+) counts ≥350
cells/ L and no history of AIDS-defining opportunistic infections within the last 12
months.
- - Participants with Hepatitis B will be excluded unless the following criteria can be
met: If the participant is hepatitis B core antibody (HbcAb) positive or hepatitis B
surface antigen (HbsAg) negative, then hepatitis B virus (HBV) deoxyribonucleic acid
(DNA) should be undectectable at the time of screening; If HbsAg+ at screening or <=3
months prior to first dose of study treatment, then HBV DNA should be undetectable,
highly effective antiviral treatment should be started ≥4 weeks prior to first dose of
study treatment.
Participants with cirrhosis are excluded.
- - 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
unless the participant can meet the following criteria: RNA test negative and
Successful anti-viral treatment (usually 8 weeks duration) is required, followed by a
negative HCV RNA test after a washout period of at least 4 weeks prior to first dose.
- - 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.
