Inclusion Criteria:
- - Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, 2.
- - Histologically or cytologically confirmed diagnosis of multiple myeloma (MM), as
defined in International Myeloma Working Group (IMWG) criteria, and:
- Has undergone autologous stem cell transplant (SCT) or is considered transplant
ineligible.
If underwent SCT, day 0 of SCT must be > 100 days to be eligible for
the study.
- - Has had disease progression after >= 3 prior lines of anti-myeloma treatments
including one proteasome inhibitor (eg.
bortezomib, carfilzomib or ixazomib), one
immunomodulatory agent (eg.thalidomide, lenalidomide or pomalidomide) and one
anti-CD38 monoclonal antibody (eg.daratumumab or isatuximab)
- - Prior non-belantamab mafodotin anti-BCMA agent exposure is allowed; patients with
prior treatment with an anti-BCMA chimeric antigen receptor (CAR)-T or bispecific
antibody will be allowed to participate in the study.
- - 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 free light chain (FLC) assay: Involved FLC level >= 10 mg/dL (>= 100 mg/L)
and an abnormal serum free light chain ratio (< 0.26 or > 1.65)
- Note: Patients with non-secretory disease will be allowed to participate.
- - Absolute neutrophil count >= 1.0 x 10^9/L (=< 28 days prior to registration)
- Without growth factor support, blood transfusion, or platelet stimulating agents
for the past 14 days, excluding erythropoietin.
- - Hemoglobin >= 8.0 g/dL (=< 28 days prior to registration)
- Without growth factor support, blood transfusion, or platelet stimulating agents
for the past 14 days, excluding erythropoietin.
- - Platelets >= 50 x 10^9/L (=< 28 days prior to registration)
- Without growth factor support, blood transfusion, or platelet stimulating agents
for the past 14 days, excluding erythropoietin.
- - Total bilirubin =< 1.5 x upper limit of normal (ULN) (=< 28 days prior to
registration); (Isolated bilirubin >= 1.5 x ULN is acceptable if bilirubin is
fractionated and direct bilirubin is < 35%)
- Alanine aminotransferase =< 2.5 x ULN (=< 28 days prior to registration)
- Aspartate transaminase =< 2.5 x ULN (=< 28 days prior to registration)
- Estimated glomerular filtration rate (eGFR) >= 30 mL/min/1.73 m^2 (=< 28 days prior to
registration)
- As calculated by Modification of Diet in Renal Disease (MDRD) formula.
- - Spot urine (albumin/creatinine ratios [spot urine]) =< 500 mg/g (56 mg/mmol) OR urine
dipstick negative/trace (if >1+ only eligible if confirmed =< 500 mg/g [56 mg/mmol] by
albumin/creatinine ratio [spot urine from first void]) (=< 28 days prior to
registration)
- Negative pregnancy test done =< 7 days prior to registration, for persons of
childbearing potential only.
Both females and males must agree to follow the
instructions.
- - NOTE: If the urine test is positive or cannot be confirmed as negative, a serum
pregnancy test will be required.
- - Provide written informed consent which includes compliance with the requirements and
restrictions listed in the informed consent form (ICF) and in the study protocol.
- - Willingness to provide mandatory blood specimens for correlative research.
- - Willing to return to enrolling institution for follow-up (during the Active Monitoring
Phase of the study)
Exclusion Criteria:
- Active plasma cell leukemia at the time of screening.
Symptomatic amyloidosis, active
POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal
plasmaproliferative disorder, myeloma protein, and skin changes), Waldenstrom
Macroglobulinemia.
- - Participant has received an investigational drug or approved systemic anti-myeloma
therapy (including systemic steroids) =< 14 days or 5 half-lives, whichever is
shorter, prior to registration.
This includes prior treatment with a monoclonal
antibody =< 30 days of receiving the first dose of study drugs. The only exception is
emergency use of a short course of systemic corticosteroids (equivalent to, or less
than: dexamethasone 40 mg/day for a maximum of 4 days) before treatment.
- - Prior belantamab mafodotin therapy.
However, patients with prior exposure to another
non-belantamab mafodotin anti-BCMA agent such as an anti-BCMA CAR-T or anti-BCMA
bispecific antibody will be allowed to participate in the study.
- - Systemic active infection requiring treatment.
- - Any unresolved toxicity >= grade 2 from previous treatment except for alopecia, or
peripheral neuropathy up to grade 2.
- - Any major surgery =< 4 weeks prior to registration.
- - 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 > 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 electrocardiogram (ECG) abnormalities including 2nd degree
(Mobitz type II) or 3rd degree atrioventricular (AV) block.
- - History of myocardial infarction (=< 6 months), acute coronary syndromes
(including unstable angina), coronary angioplasty, or stenting or bypass grafting
within 12 weeks 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, unless the participant can meet
all of the following criteria:
- Established anti-retroviral therapy (ART) for at >=4 weeks and HIV viral load <
400 copies/mL.
- - CD4+ T-cell (CD4+) counts >= 350 cells/uL.
- - No history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic
infections < 12 months prior.
- - Note: consideration must be given to ART and prophylactic antimicrobials that may
have a drug-drug interaction and/or overlapping toxicities with belantamab
mafodotin or other combination products as relevant.
- - Patients with hepatitis B will be excluded unless the following criteria can be met:
- If patient's serology shows hepatitis B virus core antibody (HbcAb)+ and
hepatitis B surface antigen (HbsAg)-, they must have undetectable hepatitis B
virus (HBV) deoxyribonucleic acid (DNA) at screening.
Patients will be monitored
per protocol. Antiviral treatment would be instituted if HBV DNA becomes
detectable.
- - If patient's serology shows HBsAg+ at screen or within 3 months prior, patients
must have undetectable HBV DNA at screening, must have started highly effective
antiviral treatment at least 4 weeks prior to registration, and must have
baseline imaging per protocol (patients with cirrhosis are excluded).
Patients
must remain on antiviral treatment throughout the study. Patients will be
monitored per protocol.
- - Note: presence of hepatitis (Hep) B surface antibody (HBsAb) indicating previous
vaccination will not exclude a participant.
- - Positive hepatitis C antibody test result or positive hepatitis C ribonucleic acid
(RNA) test result at screening or =< 12 weeks prior to first dose of study treatment
unless the participant can meet the following criteria:
- RNA test negative.
- - Successful anti-viral treatment (usually 8 weeks duration) is required, followed
by a negative HCV RNA test after a washout period >= 4 weeks.
- - Current corneal epithelial disease except for mild punctuate keratopathy.
- - Participant who received plasmapheresis within =< 7 days prior to registration.
- - Patients who received prior allogeneic stem cell transplant.
- - Participant who received a live or live-attenuated vaccine =< 30 days prior to
registration.
Ok to receive coronavirus disease (COVID) vaccine at any timepoint
during protocol treatment.
- - Participant is a woman who is pregnant or lactating.
- - Participant who plans on wearing contact lenses during treatment with belantamab
mafodotin.
Lifestyle Considerations:
Contact lenses are prohibited for participants while they are receiving belantamab
mafodotin treatment. Contact lens use may be restarted after belantamab mafodotin treatment
is discontinued, provided a qualified eye care specialist confirm there are no other
contraindications. Use of bandage contact lenses is allowed for the treatment of corneal
epithelial disease as prescribed by an ophthalmologist/eye care professional.
No other lifestyle restrictions are required for participants in this study.
