This open-label, randomized study for evaluating the efficacy and safety of single agent
belantamab mafodotin when compared to pom/dex in participants with RRMM. Participants will be
randomized in a 2:1 ratio to receive either single agent belantamab mafodotin or pom/dex.
Belantamab mafodotin will be administered intravenously at 2.5 milligram (mg)/kilogram (kg)
on Day 1 (D1) of an every 3 weeks (Q3W) schedule. Pomalidomide will be administered orally at
the approved starting dose of 4 mg daily on Days 1 to 21 of each 28-day cycle, with
dexamethasone administered orally at a dose of 40 mg once weekly (Days 1, 8, 15, and 22).
Participants in both arms will be treated until disease progression, death, unacceptable
toxicity, withdrawal of consent, and lost to follow-up or end of study, whichever comes
first. Approximately up to 380 participants will be randomized (320 + 60 to fulfill regional
- Capable of giving signed informed consent.
- Participants must be 18 or older, at the time of signing the informed consent. In
Republic of Korea, participants must be over 19 years of age inclusive, at the time of
signing informed consent.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
- Histologically or cytologically confirmed diagnosis of Multiple myeloma (MM) as
defined according to IMWG, and : Has undergone autologous stem cell transplant (SCT),
or is considered transplant ineligible; Has received at least 2 prior lines of
anti-myeloma treatments, including at least 2 consecutive cycles of both lenalidomide
and a proteasome inhibitor (given separately or in combination), and must have
documented disease progression on, or within 60 days of, completion of the last
treatment as defined by IMWG.
- Has measurable disease with at least one of the following: Serum M-protein >=0.5 gram
per deciliter (g/dL) (>=5 gram per Liter); Urine M-protein >=200 mg/24 hours; Serum
free light chain (FLC) assay: Involved FLC level >=10 milligram per deciliter (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: Transplant was >100 days prior to
initiating study treatment; No active infection(s).
- Adequate organ system functions as defined: Absolute neutrophil count (ANC)
>=1.0*10^9/L; Hemoglobin >= 8.0 g/dL; Platelets >= 50x10^9/L; Total bilirubin <=1.5*
Upper limit of normal (ULN) (isolated bilirubin >1.5*ULN is acceptable if bilirubin is
fractionated and direct bilirubin <35 percent); ALT <=2.5*ULN; Estimated glomerular
filtration rate (eGFR) >=30 milliliter per minute per 1.73 square meter (mL/min/1.73
m^2); Spot urine (albumin/creatinine ratios) <=500 milligram per gram (mg/g) (56
milligram per millimoles [mg/mmol]); Left ventricular ejection fraction (LVEF)
(echocardiogram) Clinically asymptomatic participants with ECHO confirmed LVEF>=25
- Contraceptive use by men or women 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 5 months after the last dose of study intervention
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 depending on whether they are
randomised to Arm 1 (belantamab mafodotin) or Arm 2 (pom/dex), even if they have
undergone a successful vasectomy: Agree to use a male condom throughout study
treatment including the 5 month* follow-up period even if they have undergone a
successful vasectomy and a female partner to use an additional highly effective
contraceptive method with a failure rate of <1 percent per year when having sexual
intercourse with a pregnant woman or a woman of childbearing potential who is not
currently pregnant. * Four weeks for male participants on Treatment Arm 2 (pom/dex).
- 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 agrees to abide by the following: Arm
1 (belantamab mafodotin): Use a contraceptive method that is highly effective (with a
failure rate of <1 percent per year) which includes abstinence, preferably with low
user dependency during the intervention period and for 8 months after the last dose of
study treatment. Arm 2 (pom/dex): Due to pomalidomide being a thalidomide analogue
with risk for embryofetal 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 pomalidomide, during therapy,
during dose interruptions and continuing for at least 4 weeks following
discontinuation of pomalidomide treatment. Two negative pregnancy tests must be
obtained prior to initiating therapy. The first test should be performed within 10-14
days and the second test within 24 hours prior to prescribing pomalidomide therapy.
And agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during
this period. The investigator should confirm the effectiveness of the contraceptive
method(s) ahead of the first dose of study intervention.
- All prior treatment-related toxicities (defined by National Cancer Institute- Common
Toxicity Criteria for Adverse Events [NCI-CTCAE], version 5.0, 2017) must be <=Grade 1
at the time of enrollment, except for alopecia and Grade 2 peripheral neuropathy.
- In France, a participant will be eligible for inclusion in this study only if either
affiliated to or a beneficiary of a social security category.
- Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly,
endocrinopathy, myeloma protein, and skin changes); active plasma cell leukemia at the
time of screening.
- Systemic anti-myeloma therapy or use of an investigational drug within <14 days or 5
half-lives, whichever is shorter, before the first dose of study intervention.
- Prior treatment with an anti-MM monoclonal antibody within 30 days prior to receiving
the first dose of study intervention.
- Prior B cell maturation antigen (BCMA)-targeted therapy or prior pomalidomide
- Plasmapheresis within 7 days prior to the first dose of study intervention.
- Prior allogeneic stem cell transplant.
- Any major surgery within the last 4 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 fulfil 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 with study procedures.
- History of (non-infectious) pneumonitis that required steroids, or current
- Evidence of active mucosal or internal bleeding.
- Current unstable liver or biliary disease per investigator assessment defined by the
presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or
gastric varices, persistent jaundice, or cirrhosis.
- Participants with previous or concurrent 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.
- Evidence of cardiovascular risk including any of the following: QT interval corrected
for heart rate by Fridericia's formula (QTcF) >= 480 millisecond (msec); Evidence of
current clinically significant uncontrolled arrhythmias including clinically
significant electrocardiogram (ECG) abnormalities including 2nd degree (Mobitz Type
II) or 3rd degree atrioventricular 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 (NYHA) functional classification system;
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to belantamab mafodotin, pomalidomide, dexamethasone or any of the
components of the study intervention.
- Pregnant or lactating female.
- Active infection requiring treatment.
- Known human immunodeficiency virus (HIV).
- 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 intervention.
- 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
- Participants unable to tolerate thromboembolic prophylaxis.