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

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 3 months. Contraindications to or unwilling to undergo protocol-required anti-thrombotic prophylaxis

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.

Participant is exhibiting signs of meningeal or central nervous system involvement with MM.

Part 2: Current corneal epithelial disease except nonconfluent Superficial punctate keratitis (SPK).

Has cirrhosis or current unstable liver or biliary disease per investigator assessment 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 any other malignancy from which the participant has been disease-free for more than 2 years and, in the opinion of the Principal investigator (PI) and GlaxoSmithKline (GSK) Medical Director, will not affect the evaluation of the effects of this clinical trial treatment on the currently targeted malignancy (MM). Participants on active surveillance or hormone treatment for non-metastatic prostate cancer are not excluded. Participants on hormone therapy for non-metastatic breast cancer are not excluded

Evidence of cardiovascular risk including any of the following:

* Evidence of current clinically significant untreated arrhythmias, including, but not limited to, clinically significant Electrocardiogram (ECG) abnormalities such as 2nd degree (Mobitz Type II) or 3rd degree Atrioventricular (AV) block.

* Part 1 dose escalation and Part 2 only: QT interval corrected using Fridericia's formula (QTcF) interval \>480 millisecond (msec) (QT interval corrected for heart rate according to Fridericia's formula), and/or hypokalemia, and/or family history of long QT syndrome.

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

* History of MI, acute coronary syndromes (including unstable angina), coronary angioplasty, 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 drugs chemically related to belantamab / belantamab mafodotin or any of the components of the study treatment. History of severe hypersensitivity to other Monoclonal antibodies (mAbs).

Active infection requiring antibiotic, antiviral, or antifungal treatment.

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

Known Human immunodeficiency virus (HIV) infection, unless the participant can meet specific criteria.

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

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

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.

Part 1: Refractory to belantamab mafodotin (confirmed PD as per IMWG criteria while on belantamab mafodotin therapy or within 60 days of completing that treatment). Prior belantamab mafodotin is allowed if it was discontinued due to toxicity which subsequently resolved. Note: Prior treatment with other anti- B-cell maturation antigen (BCMA) directed agents is allowed. Provided there is at least 6-month washout after the last dose of prior anti-BCMA therapy.

Part 2: Prior belantamab mafodotin therapy is not allowed. Prior treatment with other anti-BCMA directed agents is allowed provided there is at least a 6-month washout after the last dose of prior anti-BCMA 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 stem cells transplant.

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 dose or has not recovered fully from surgery.

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

Part 1 dose escalation only: Has received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including Granulocyte colony stimulating 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. This does not apply for Part 1 Expansion Cohort.

Part 3: Prior belantamab, belantamab mafodotin, and pomalidomide therapy are not allowed. Prior treatment with other anti- 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 to first dose of study treatment or whilst receiving belantamab for at least 70 days following last study treatment.

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 this trial, unless prospective Independent Review Board (IRB) approval (by chair or designee) is allowing exception to this criterion for a specific participant.

The use of other anti-cancer therapy not specified in this protocol, and any investigational agents other than belantamab and belantamab mafodotin, or any other MM Standard of Care (SoC) agents other than pomalidomide or dexamethasone are explicitly prohibited for the duration of the study.

What this study is about