Inclusion Criteria:
- Capable of giving signed informed consent.
- Male or female, 18 years or older (at the time consent is obtained).
- Have confirmed diagnosis of Multiple Myeloma (MM) as defined by the IMWG.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 for Arm A and 0
to 2 for Arm B.
- Have undergone stem cell transplant (SCT), or are considered transplant ineligible.
- Have been previously treated with at least 1 prior line of MM therapy, and must have
documented disease progression during or after their most recent therapy.
- Must have at least ONE aspect of measurable disease, defined as one the following:
Urine M-protein excretion >=200 milligram (mg)/24 hours, or; Serum M-protein
concentration >=0.5 gram (g)/deciliter (dL) (>=5.0 g/Liter), or; 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).
- Participants with a history of autologous SCT, are eligible for study participation
provided the following eligibility criteria are met: Autologous SCT was >100 days
prior to study enrollment; No active bacterial, viral, or fungal infection(s) present;
Participant meets the remainder of the eligibility criteria.
- All prior treatment-related toxicities (defined by National Cancer Institute Common
Toxicity Criteria for Adverse Events [NCI-CTCAE], Version 4.03, 2010) must be Grade <=
1 at the time of enrollment, except for alopecia. Participants with Grade 2 neuropathy
can be enrolled into Len/Dex treatment arm, but not into Bor/Dex treatment arm.
- Adequate organ system functions as defined by the laboratory assessments.
- The contraceptions used by female participants be consistent with local regulations,
regarding 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 child bearing
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
belantamab mafodotin and agrees not to donate eggs (ova, oocytes) for the purpose of
reproduction during this period. 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.
WOCBP Participants Assigned to Arm A:
- Due to lenalidomide being a thalidomide analogue with risk for embryo-fetal toxicity
and prescribed under a pregnancy prevention/controlled distribution program, WOCBP
participants will be eligible if they commit either to abstain continuously from
heterosexual sexual intercourse or to use two methods of reliable birth control (one
method that is highly effective; beginning 4 weeks prior to initiating treatment with
lenalidomide, during therapy, during dose interruptions and continuing for 4 weeks
following discontinuation of lenalidomide treatment. Thereafter, WOCBP participants
must use a contraceptive method that is highly effective (with a failure rate of <1%
per year) for a further 3 months, and agree not to donate eggs (ova, oocytes) for the
purpose of reproduction during this period: Two negative pregnancy tests must be
obtained prior to initiating lenalidomide therapy. The first test should be performed
within 10-14 days and the second test within 24 hours prior to prescribing
lenalidomide therapy.
WOCBP Participants Assigned to Arm B
- WOCBP assigned to Arm B must have a negative highly sensitive serum pregnancy test
within 72 hours of dosing on C1D1 and agree to use effective contraception during the
study and for 4 months after the last dose of belantamab mafodotin or 7 months from
the last dose of bortezomib, whichever is longer.
- Male participants using contraception 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:
Arm A: from the time of first dose of study until 6 months after the last dose of
belantamab mafodotin 4 weeks after the last dose of lenalidomide, whichever is longer, to
allow for clearance of any altered sperm.
Arm B: from the time of first dose of study until 6 months after the last dose of
belantamab mafodotin or 4 months from the last dose of bortezomib (whichever is the longer)
to allow for clearance of any altered sperm.
- Male participants must agree to 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. Male participants should
also use a condom with pregnant females. If the female partner of the male participant
is pregnant at the time of enrollment, or becomes pregnant during the trial, the male
participant must agree to remain abstinent (if it is consistent with their preferred
and usual lifestyle) or use a male condom.
Exclusion Criteria:
- Systemic anti-myeloma therapy (including systemic steroids) within <=14 days, or
plasmapheresis within 7 days prior to the first dose of study drug.
- Use of an investigational drug within 14 days or five half-lives (whichever is longer)
preceding the first dose of study drug.
- Prior treatment with a monoclonal antibody within 30 days of receiving the first dose
of study drugs.
- Prior allogenic stem cell transplant. Note: Participants who have undergone syngeneic
transplant will be allowed only if they have no history and no currently active, graft
versus host disease (GvHD).
- Evidence of active mucosal or internal bleeding.
- Any major surgery within the last four weeks.
- Presence of active renal condition (infection, requirement for dialysis or any other
condition that could affect participant's safety). Participants with isolated
proteinuria resulting from MM are eligible, provided they fulfill criteria.
- Any serious and/or unstable pre-existing medical, psychiatric disorder or other
conditions (including lab abnormalities) that could interfere with participant's
safety, obtaining informed consent or compliance to the study procedures.
- Current active liver or biliary disease (with the exception of Gilbert's syndrome or
asymptomatic gallstones, or otherwise stable chronic liver disease per investigator's
assessment).
- Participants with invasive malignancies other than multiple myeloma are excluded,
unless the second 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 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 uncontrolled arrhythmias, including clinically significant ECG
abnormalities including 2nd degree (Type II) or 3rd degree atrioventricular (AV)
block; 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.
- 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.
- Pregnant or lactating female.
- Active infection requiring treatment.
- Known Human immunodeficiency virus (HIV) infection.
- Presence of hepatitis B surface antigen (HBsAg), or hepatitis B core antibody (HBcAb
at Screening or within 3 months prior to first dose of study treatment).
- Current corneal disease except for mild punctuate keratopathy.
- Positive hepatitis C antibody test result or positive hepatitis C Ribonucleic acid
(RNA) test result at Screening or within 3 months prior to first dose of study
treatment.
- Current corneal disease except for mild punctute keratopathy.
- Participants Assigned to Treatment A (belantamab mafodotin plus Len/Dex): Participants
unable to tolerate antithrombotic prophylaxis must be excluded; Discontinuation of
prior treatment with lenalidomide due to intolerable AEs.
- Participants Assigned to Treatment B (belantamab mafodotin plus Bor/Dex): Unacceptable
AEs from previous bortezomib treatment; Ongoing Grade 2 or higher peripheral
neuropathy or neuropathic pain from previous bortezomib treatment; Intolerance or
contraindications to anti-viral prophylaxis.
