Inclusion Criteria:
1. Participant must be ≥18 years or older.
2. Documented diagnosis of Multiple Myeloma (MM) as per International Myeloma Working
Group (IMWG) criteria.
3. Must have at least ONE aspect of measurable disease, defined as one of the following:
1. Urine M-protein excretion ≥200 mg/24 hrs (≥0.2 g/24 hrs), or. 2. Serum M-protein concentration ≥0.5 g/dL (≥5.0 g/L), or. 3. Serum Free Light Chain (FLC) assay: involved FLC level ≥10 mg/dL (≥100 mg/L) and
an abnormal serum FLC ratio (<0.26 or >1.65).
4. Eastern Cooperative Oncology Group performance status of 0-2.
5. Adequate organ system function as defined by the below laboratory assessments.
Hematologic. 1. Absolute neutrophil count (ANC) ≥1.5 X 109/L; granulocyte colony stimulating
factor use within the past 14 days is NOT permitted.
2. Hemoglobin ≥8.0 g/dL; transfusions within the past 14 days are NOT permitted.
Erythropoietin use is allowed.
3. Platelet count ≥50 x 109/L if Bone Marrow (BM) is >50% involved in myeloma.
Otherwise ≥75 x 109/L; transfusions within the past 14 days are NOT allowed to
reach this level.
Hepatic. 1. Total bilirubin ≤1.5xULN (isolated bilirubin ≥1.5xULN is acceptable if bilirubin
is fractionated and direct bilirubin <35%).
2. Alanine aminotransferase (ALT) ≤ 2.5xUpper Limit of Normal (ULN). Renal. 1. Estimate glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2; calculated using
the Modified Diet in Renal Disease (MDRD) formula.
2. Spot urine (albumin/creatinine ratio) ≤500 mg/g (56 mg/mmol) OR. 3. 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).
6. Female participants: contraceptive use 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) defined as follows:
1.
≥45 years of age and has not had menses for > 1 year. 2. Participants who have been amenorrhoeic for < 2 years without history of a
hysterectomy and oophorectomy must have a follicle stimulating hormone value
in the postmenopausal range upon screening evaluation. 3. Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation.
Documented hysterectomy or oophorectomy must be confirmed with medical
records of the actual procedure or confirmed by an ultrasound. Tubal
ligation must be confirmed with medical records of the actual procedure.
OR.
- - Is a WOCBP and using two methods of reliable birth control (one method that is
highly effective and one additional effective [barrier] method), beginning 4
weeks before initiating treatment with pomalidomide, during therapy, during dose
interruptions, and continuing for 4 weeks following discontinuation of
pomalidomide treatment.
WOCBP participants must use one method of reliable birth
control that is highly effective for 4 months following discontinuation of
belantamab mafodotin or 3 months following the discontinuation of daratumumab.
WOCBP must also agree not to donate eggs (ova, oocytes) for the purpose of
reproduction during treatment, during dose interruptions and for 28-days
following the last dose of pomalidomide or 3 months following discontinuation of
daratumumab treatment or 4 months following discontinuation of belantamab
mafodotin treatment whichever is longer.
A WOCBP must have two negative pregnancy tests before therapy initiation. The first
test should be performed within 10-14 days and the second test within 24 hours before
the start of pomalidomide therapy.
The participant should not receive pomalidomide until the Investigator has verified
that the results of these pregnancy tests are negative. The Investigator should
evaluate the effectiveness of the contraceptive method in relationship to the first
dose of study treatment. The Investigator is responsible for a review of medical
history, menstrual history, and recent sexual activity to decrease the risk for
inclusion of a woman with a nearly undetected pregnancy.
7. Male participants: contraceptive use 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 during
the intervention period and until 28 days after the last dose of pomalidomide or 3
months following the discontinuation of daratumumab or 6 months after the last dose of
belantamab mafodotin, whichever is longer, to allow for clearance of any altered
sperm.
• Refrain from donating sperm. PLUS 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 as when having sexual intercourse with a woman of
childbearing potential (including pregnant females).
8. Participants must be able to understand the study procedures and agree to participate
in the study by providing written informed consent.
9. Participant must have received only 1 prior line of therapy (including lenalidomide)
and be lenalidomide refractory at any lenalidomide dose (i.e., nonresponsive while on
lenalidomide therapy, or progresses within 60 days of last therapy with lenalidomide).
Exclusion Criteria:
1. Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the
National Cancer Institute, Common Toxicity Criteria for Adverse Events (NCI CTCAE)
Version 5.
2. Major surgery within 4 weeks before the first dose of study drug.
- - NOTE 1: participant must be clinically stable following a major surgery to be
entered in the study.
- - NOTE 2: major surgery shall be defined based on the Investigator's judgment
according to the extent and complexity of the procedure, its pathophysiological
consequences and consecutive clinical outcomes.
3. Presence of active renal condition (infection, requirement for dialysis, or any other
significant condition that could affect participant's safety). Participants with
isolated proteinuria resulting from MM are eligible, provided that they fulfil the
other inclusion criteria.
4. Any serious and/or unstable pre-existing medical or psychiatric disorder, or other
conditions (including laboratory abnormalities) that could interfere with
participant's safety, obtaining informed consent, or compliance to the study
procedures.
5. Evidence of active mucosal or internal bleeding uncontrolled by local therapy and not
explained by reversible coagulopathy.
6. Current active unstable liver or biliary disease defined by the presence of ascites,
encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices,
persistent jaundice, or cirrhosis (except for Gilbert's syndrome or asymptomatic
gallstones; otherwise, stable non-cirrhotic chronic liver disease; or hepatobiliary
involvement of malignancy as per the Investigator's assessment).
7. Participants with previous or concurrent malignancies other than MM are excluded.
Exceptions are surgically treated cervical carcinoma in situ, or any other malignancy
that 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 non-melanoma skin cancer are allowed
without a 2-year restriction.
8. Evidence of cardiovascular risk including any of the following:
- - Evidence of current clinically significant untreated arrhythmias, including
clinically significant electrocardiogram (ECG) abnormalities, second degree
(Mobitz Type II), or third degree atrioventricular block.
- - Screening 12-lead ECG showing a baseline QT interval >470 msec.
- - 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.
- - Uncontrolled hypertension.
9. Participant has known chronic obstructive pulmonary disease (COPD) (defined as a
forced expiratory volume in 1 second [FEV1] <50% of predicted normal), persistent
asthma, or a history of asthma within the last 2 years (controlled intermittent asthma
or controlled mild persistent asthma is allowed).
NOTE: Participants with known or suspected COPD must have a FEV1 test at screening.
10. Active infection requiring treatment.
11. Known human immunodeficiency virus infection, unless the participant can meet all of
the following criteria:
- - Established anti-retroviral therapy for at least 4 weeks and HIV viral load <400
copies/mL.
- - CD4+ T-cell (CD4+) count ≥350 cells/uL.
- - No history of AIDS-defining opportunistic infections within the last 12 months.
- - 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.
12. To be seropositive for hepatitis B (defined by a positive test for hepatitis B surface
antigen [HBsAg]) at screening or within 3 months prior to first dose of study
treatment.
- - NOTE 1: Participants with resolved infection (i.e., participants who are positive
for antibodies to hepatitis B core antigen [antiHBc] or antibodies to hepatitis B
surface antigen [antiHBs]) must be screened using real-time polymerase chain
reaction (PCR).
Those who are PCR positive will be excluded.
- - NOTE 2: presence of antiHBs indicating previous vaccination will not constitute
an exclusion criterion.
13. Positive hepatitis C antibody test result or positive hepatitis C RNA test result at
screening or within 3 months before the first dose of study treatment unless the
participant can meet the following criteria:
- - Successful anti-viral treatment (usually 8 weeks duration) is required, followed
by a negative hepatitis C virus (HCV) RNA test after a washout period of at least
4 weeks.
14. Current corneal epithelial disease except for mild punctate keratopathy.
- - NOTE: Participants with mild punctate keratopathy are allowed.
15. Intolerance or contraindications to anti-viral prophylaxis.
16. Unable to tolerate antithrombotic prophylaxis.
17. Active or history of venous thromboembolism within past 3 months.
18. AL amyloidosis (light chain amyloidosis), active POEMS syndrome (polyneuropathy,
organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, skin changes)
or active plasma cell leukemia at the time of screening.
19. Exhibiting clinical signs of or with a known history of meningeal or central nervous
system involvement by MM.
20. Known intolerance or immediate or delayed hypersensitivity reaction or idiosyncratic
reaction to: drugs chemically related to belantamab mafodotin, or any of the
components of the study treatment; daratumumab subcutaneous (SC) or to any of its
excipients; or infused protein products, sucrose, histidine, and polysorbate 80.
21. Use of an investigational drug within 14 days or 5 half-lives (whichever is longer)
preceding the first dose of study drug.
22. Participant who has received prior treatment with daratumumab, pomalidomide or
belantamab mafodotin will be excluded.
- - NOTE: Participants who received induction treatment with daratumumab (max 4
cycles) will be allowed as long as 6 months have passed since their treatment
with daratumumab and cycle 1 day 1 (C1D1).
23. Plasmapheresis within 7 days before the first dose of study drug.
24. Participants with uncontrolled skin disease.
25. Participant must not have received a live or live-attenuated vaccine within 30 days
prior to first dose of belantamab mafodotin.
26. Participant should not use contact lenses while receiving belantamab mafodotin.
