A Study to Investigate the Safety and Efficacy of Belantamab for the Treatment of Multiple Myeloma When Used as Monotherapy and in Combination Treatments

Inclusion Criteria:

• Participants at the time of signing the Informed Consent Form (ICF) are at least 18years old or are of the legal age of consent in the jurisdiction in which the studyis taking place.

• Participants who have histologically or cytologically confirmed diagnosis ofMultiple Myeloma (MM), as defined by the international myeloma working group (IMWG)and have progressed on or following the last line of treatment Part 1 and Part 2:Participants who have received at least 3 prior lines of anti-myeloma treatments, ,including lenalidomide, a proteasome inhibitor, and an anti-CD38 mAb either incombination or separately.

• Part 3: Have received at least 1 prior line of treatment anti-myeloma treatments,including lenalidomide. Prior anti-CD38-containing regimen is not mandated, howeverno more than 70% of participants recruited may be anti-CD38 naïve

• Participants with a history of Autologous stem cell transplant (ASCT) are eligiblefor study participation provided the following eligibility criteria are met:

• Transplant was greater than (>)100 days prior to screening.

• No active bacterial, viral, or fungal infection(s) present

• Eastern cooperative oncology group-performance status (ECOG-PS) of 0 to 2.

• Measurable disease defined as at least ONE of the following:

• Serum M-protein concentration greater than (>=) 0.5 gram (g)/ deciliter (dL) (>=5gram/liter [g/L])

• Urine M-protein excretion >=200 milligram(mg)/24 hours (>=0.2 g/24 hours)

• Serum free light chain (FLC) assay: involved FLC level >=10 mg/dL (>=100 milligramsper liter [mg/L]) and an abnormal serum FLC ratio (less than [<]0.26 or >1.65)

• Have adequate organ system function as defined by the laboratory assessments

• All prior treatment-related toxicities (defined by National Cancer Institute-CommonToxicity Criteria for Adverse Events [NCI-CTCAE], v5.0, 2017) must be Grade <=1 atthe time of screening except for alopecia (any grade), neuropathy (Grade <=2), orendocrinopathy managed with replacement therapy (any grade).

• Participants or legally authorized representative (LAR) capable of giving signedinformed consent, which includes compliance with the requirements and restrictionslisted in the ICF and in this protocol.

• Contraceptive use by women should be consistent with local regulations regarding themethods of contraception for those participating in clinical studies.

• 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 Participant of child-bearing potential (POCBP) or

• Is a POCBP and using a contraceptive method that is highly effective (with a failurerate of <1% per year), preferably with low user dependency during the interventionperiod and for 4 months after the last dose of study intervention and agrees not todonate eggs (ova, oocytes) for the purpose of reproduction during this period. Theinvestigator should evaluate the effectiveness of the contraceptive method inrelationship to the first dose of study intervention.

• Part 3: Due to pomalidomide being a thalidomide analogue with a risk for embryofetaltoxicity and prescribed under a pregnancy prevention/controlled distributionprogramme, POCBP will be eligible if they commit either to abstain continuously fromheterosexual sexual intercourse or use two methods of reliable birth control (onemethod that is highly effective plus an additional barrier method), beginning atleast 4 weeks prior to initiating treatment with pomalidomide, during therapy,during dose interruptions and continuing for at least 4 weeks followingdiscontinuation of pomalidomide treatment. Thereafter, POCBP must use onecontraceptive method that is highly effective (with a failure rate of less than (<)1percentage (%) per year) for a further 3 months (total 4 months).

• The investigator should evaluate the effectiveness of the contraceptive method inrelationship to the first dose of study intervention

• All POCBP must agree not to donate eggs (ova, oocytes) for the purpose ofreproduction during this period

Exclusion Criteria:

• Diagnosis of primary Amyloid Light chain (AL) Amyloidosis, active Polyneuropathy,organomegaly, endocrinopathy, myeloma protein, and skin changes (POEMS) syndrome,primary plasma cell leukemia.

• Part 3: Active or history of venous or arterial thromboembolism within the past 3months. Contraindications to or unwilling to undergo protocol-requiredanti-thrombotic prophylaxis

• 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.

• Participant is exhibiting signs of meningeal or central nervous system involvementwith MM.

• Current corneal epithelial disease except nonconfluent Superficial punctatekeratitis (SPK).

• Has cirrhosis or current unstable liver or biliary disease per investigatorassessment defined by the presence of ascites, encephalopathy, coagulopathy,hypoalbuminemia, esophageal/gastric varices, or persistent jaundice.

• Presence of malignancies other than disease under study are excluded, except for anyother malignancy from which the participant has been disease-free for more than 2years and, in the opinion of the Principal investigator (PI) and GlaxoSmithKline (GSK) Medical Director, will not affect the evaluation of the effects of thisclinical trial treatment on the currently targeted malignancy (MM).Participants onactive surveillance or hormone treatment for non-metastatic prostate cancer are notexcluded. Participants on hormone therapy for non-metastatic breast cancer are notexcluded

• Evidence of cardiovascular risk including any of the following:

• Evidence of current clinically significant untreated arrhythmias, including, but notlimited to, clinically significant Electrocardiogram (ECG) abnormalities such as 2nddegree (Mobitz Type II) or 3rd degree Atrioventricular (AV) block.

• Part 1 dose escalation and Part 2 only: QT interval corrected using Fridericia'sformula (QTcF) interval >480 millisecond(msec) (QT interval corrected for heart rateaccording to Fridericia's formula), and/or hypokalemia, and/or family history oflong QT syndrome.

• Part 1 dose expansion and Part 3: Not applicable.

• History of MI, acute coronary syndromes (including unstable angina), coronaryangioplasty, stenting or bypass grafting, all within three months of screening.

• Class III or IV heart failure as defined by the New York Heart Association (NYHA)functional classification system.

• Uncontrolled hypertension

• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugschemically related to Unconjugated belantamab antibody / belantamab mafodotin or anyof the components of the study treatment. History of severe hypersensitivity toother Monoclonal antibodies (mAbs).

• Active infection requiring antibiotic, antiviral, or antifungal treatment.

• For serology of HBsAg+ at screen or within 3 months prior to first dose Japan only:must test hepatitis B e-antigen (HBeAg) and antibody to hepatitis B e-antigen (HBeAb.) Eligibility verification should be evaluated and agreed with a hepatologist (after they record the approval in the patient medical record).

• Known Human immunodeficiency virus (HIV) infection, unless the participant can meetspecific criteria.

• Recent history (within the past 6 months) of acute diverticulitis, inflammatorybowel disease, intra-abdominal abscess, or gastrointestinal obstruction.

• Participants with Hepatitis B virus (HBV) or Hepatitis C virus (HCV) will beexcluded unless specific criteria can be met.

• 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.

• Part 1: Refractory to belantamab mafodotin (confirmed PD as per IMWG criteria whileon belantamab mafodotin therapy or within 60 days of completing that treatment).Prior belantamab mafodotin is allowed if it was discontinued due to toxicity whichsubsequently resolved Note: Prior treatment with other anti-BCMA directed agents isallowed. Provided there is at least 6-month washout after the last dose of prioranti-BCMA therapy.

• Part 2: Prior belantamab mafodotin therapy is not allowed. Prior treatment withother anti-BCMA directed agents is allowed provided there is at least a 6-monthwashout after the last doseof prior anti-BCMA therapy to start of study therapy.

• Prior radiotherapy within 2 weeks of start of study therapy.

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

• Prior allogeneic transplant is prohibited.

• Participants who have received prior Chimeric Antigen Receptor T-cell therapy (CAR-T) therapy with lymphodepletion with chemotherapy within 3 months of screening.

• Any major surgery (other than bone-stabilizing surgery) within 2 weeks of first doseor has not recovered fully from surgery.

• Prior treatment with a mAb within 30 days of receiving the first dose of studydrugs, or treatment with an investigational agent or approved systemic anti-myelomatherapy (including systemic steroids) within 14 days or 5 half-lives of receivingthe first dose of study drugs, whichever is longer.

• Part 1: Has received transfusion of blood products (including platelets or red bloodcells) or administration of colony stimulating factors (including Granulocyte colonystimulating factor (G-CSF), Granulocyte-macrophage colony-stimulating factor (GMCSF), recombinant erythropoietin) or any thrombopoietin receptor agonists within 2 weeks before the first dose of study drug.

• Part 3:Prior Unconjugated belantamab antibody, belantamab mafodotin, andpomalidomide therapy. are not allowed. Prior treatment with other anti- B-cellmaturation antigen (BCMA) directed agents is allowed provided there is at least 6-month washout after the last dose of prior anti-BCMA therapy.

• Participants must not receive live/live attenuated vaccines within 30 days prior tofirst dose of study treatment or whilst receiving Unconjugated belantamab antibodyfor at least 70 days following last study treatment.

• Known, current drug or alcohol abuse.

• Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling,or child) who is investigational site or Sponsor staff directly involved with thistrial, unless prospective Independent Review Board (IRB) approval (by chair ordesignee) is allowing exception to this criterion for a specific participant