Study of Single Agent Belantamab Mafodotin Versus Pomalidomide Plus Low-dose Dexamethasone (Pom/Dex) in Participants With Relapsed/Refractory Multiple Myeloma (RRMM)

Inclusion Criteria:

• Capable of giving signed informed consent.

• Participants must be 18 or older, at the time of signing the informed consent. InRepublic of Korea, participants must be over 19 years of age inclusive, at the timeof signing informed consent.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

• Histologically or cytologically confirmed diagnosis of Multiple myeloma (MM) asdefined according to IMWG, and : Has undergone autologous stem cell transplant (SCT), or is considered transplant ineligible; Has received at least 2 prior linesof anti-myeloma treatments, including at least 2 consecutive cycles of bothlenalidomide and a proteasome inhibitor (given separately or in combination), andmust have documented disease progression on, or within 60 days of, completion of thelast treatment or must be non-responsive while on last treatment, wherenon-responsive is defined as not achieving at least Minimal Response (MR) after 2complete treatment cycles. In such cases lack of achieving of at least MR must bedetermined no earlier than at least 4 weeks after the last treatment.

• Has measurable disease with at least one of the following: Serum M-protein >=0.5gram 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 participationprovided the following eligibility criteria are met: Transplant was >100 days priorto initiating study treatment; No active infection(s).

• Adequate organ system functions as defined: Absolute neutrophil count (ANC) >=1.010^9/L; Hemoglobin >= 8.0 g/dL; Platelets >= 50x10^9/L; Total bilirubin <=1.5Upper limit of normal (ULN) (isolated bilirubin >1.5ULN is acceptable if bilirubinis fractionated and direct bilirubin <35 percent); ALT <=2.5ULN; Estimatedglomerular 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]).

• Contraceptive use by men or women should be consistent with local regulationsregarding the methods of contraception for those participating in clinical studies.Male participants are eligible to participate if they agree to the following duringthe intervention period and until 6 months after the last dose of study interventionto allow for clearance of any altered sperm: Refrain from donating sperm PLUS,either: Be abstinent from heterosexual intercourse as their preferred and usuallifestyle (abstinent on a long term and persistent basis) and agree to remainabstinent OR Must agree to use contraception/barrier as detailed below depending onwhether they are randomised to Arm 1 (belantamab mafodotin) or Arm 2 (pom/dex), evenif they have undergone a successful vasectomy: Agree to use a male condom throughoutstudy treatment including the 6 month follow-up period even if they have undergone asuccessful vasectomy and a female partner to use an additional highly effectivecontraceptive method with a failure rate of <1 percent per year when having sexualintercourse with a pregnant woman or a woman of childbearing potential who is notcurrently pregnant. Four weeks for male participants on Treatment Arm 2 (pom/dex).

• A female participant is eligible to participate if she is not pregnant orbreastfeeding, and at least one of the following conditions applies: Is not a womanof childbearing potential (WOCBP) OR Is a WOCBP and agrees to abide by thefollowing: Arm 1 (belantamab mafodotin): Use a contraceptive method that is highlyeffective (with a failure rate of <1 percent per year) which includes abstinence,preferably with low user dependency during the intervention period and for 4 monthsafter the last dose of study treatment. Arm 2 (pom/dex): Due to pomalidomide being athalidomide analogue with risk for embryofetal toxicity and prescribed under apregnancy prevention/controlled distribution program, WOCBP participants will beeligible if they commit either to abstain continuously from heterosexual sexualintercourse or to use two methods of reliable birth control (one method that ishighly effective), beginning 4 weeks prior to initiating treatment withpomalidomide, during therapy, during dose interruptions and continuing for at least 4 weeks following discontinuation of pomalidomide treatment. Two negative pregnancytests must be obtained prior to initiating therapy. The first test should beperformed within 10-14 days and the second test within 24 hours prior to prescribingpomalidomide therapy. And agrees not to donate eggs (ova, oocytes) for the purposeof reproduction during this period. The investigator should confirm theeffectiveness of the contraceptive method(s) ahead of the first dose of studyintervention.

• All prior treatment-related toxicities (defined by National Cancer Institute- CommonToxicity 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.

Exclusion Criteria:

• Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly,endocrinopathy, myeloma protein, and skin changes); active plasma cell leukemia atthe time of screening.

• Systemic anti-myeloma therapy or use of an investigational drug within <14 days or 5half-lives, whichever is shorter, before the first dose of study intervention.

• Prior treatment with an anti-MM monoclonal antibody within 30 days prior toreceiving the first dose of study intervention.

• Prior B cell maturation antigen (BCMA)-targeted therapy or prior pomalidomidetreatment.

• Plasmapheresis within 7 days prior to the first dose of study intervention.

• Prior allogeneic stem cell transplant. (Participants who have undergone syngeneictransplant will be allowed only if no history of, or currently active,Graft-Versus-Host Disease [GvHD]).

• Any major surgery within the last 4 weeks.

• Presence of active renal condition (infection, requirement for dialysis or any othercondition that could affect participant's safety). Participants with isolatedproteinuria resulting from MM are eligible, provided they fulfil criteria asdescribed in inclusion criteria.

• Any serious and/or unstable pre-existing medical, psychiatric disorder, or otherconditions (including lab abnormalities) that could interfere with participant'ssafety, obtaining informed consent, or compliance with study procedures.

• History of (non-infectious) pneumonitis that required steroids, or currentpneumonitis.

• Evidence of active mucosal or internal bleeding.

• Current unstable liver or biliary disease per investigator assessment defined by thepresence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal orgastric varices, persistent jaundice, or cirrhosis. (Stable chronic liver disease [including Gilbert's syndrome or asymptomatic gallstones] or hepatobiliaryinvolvement of malignancy is acceptable if participant otherwise meets entrycriteria)

• Participants with previous or concurrent malignancies other than multiple myelomaare excluded, unless the second malignancy has been considered medically stable forat least 2 years. The participant must not be receiving active therapy, other thanhormonal therapy for this disease. (Participants with curatively treatednon-melanoma skin cancer are allowed without a 2-year restriction).

• Evidence of cardiovascular risk including any of the following: Evidence of currentclinically significant uncontrolled arrhythmias including clinically significantelectrocardiogram (ECG) abnormalities including 2nd degree (Mobitz Type II) or 3rddegree atrioventricular block; History of myocardial infarction, acute coronarysyndromes (including unstable angina), coronary angioplasty, or stenting or bypassgrafting within 3 months of Screening; Class III or IV heart failure as defined bythe New York Heart Association (NYHA) functional classification system; Uncontrolledhypertension.

• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugschemically related to belantamab mafodotin, pomalidomide, dexamethasone or any ofthe components of the study intervention.

• Pregnant or lactating female.

• Active infection requiring treatment.

• Known human immunodeficiency virus (HIV), unless the participant can meet all of thefollowing criteria: Established anti-retroviral therapy (ART) for at least 4 weeksand HIV viral load <400 copies/mL; CD4+ T-cell (CD4+) counts ≥350 cells/uL; Nohistory of AIDS-defining opportunistic infections within the last 12months.(Consideration must be given to ART and prophylactic antimicrobials that mayhave a drug-drug interaction and/or overlapping toxicities with belantamab mafodotinor other combination products as relevant)

• Participants with Hepatitis B will be excluded unless the following criteria can bemet: If the participant is hepatitis B core antibody (HbcAb) positive or hepatitis Bsurface 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 beundetectable, highly effective antiviral treatment should be started ≥4 weeks priorto first dose of study treatment, exclusion of participants with cirrhosis andparticipants in Japan must test hepatitis B e antigen (HBeAg) and hepatitis B eantibody (HBeAb ).

• 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 studytreatment unless the participant can meet the following criteria: Hepatitis C RNAtest negative at Screening and successful anti-viral treatment (usually 8 weeksduration) is required, followed by a negative HCV RNA test after a washout period ofat least 4 weeks (Hepatitis RNA is optional and participants with negative HepatitisC antibody test are not required to also undergo Hepatitis C RNA testing).

• Participants unable to tolerate thromboembolic prophylaxis.

• Current corneal epithelial disease except for mild punctate keratopathy.