A Study Evaluating the Efficacy of Belantamab Mafodotin in Participants with Relapsed/Refractory Multiple Myeloma

Participants with confirmed diagnosis of multiple myeloma as defined by the International Myeloma Working Group (IMWG) criteria

• Participants previously treated with at least 1 prior line of multiple myeloma (MM) therapy (including a lenalidomide-containing regimen for DREAMM 8 study only)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Participants must have at least ONE aspect of measurable disease, defined as one the following:

Serum free light chain (FLC) assay: involved FLC level ≥10 milligrams per decilitre (mg/dL) (≥100 mg/L) and an abnormal serum free light chain ratio (1.65 for DREAMM 7 study and <0.26 or >1.65 [only if patient has no measurable urine or serum M spike] for DREAMM 8 study

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

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

• All prior treatment-related toxicities must be Grade ≤1 at the time of enrolment, except for alopecia

Exclusion criteria for DREAMM 7 and DREAMM 8 study:

• Intolerant to bortezomib or refractory to bortezomib
• Plasmapheresis within 7 days prior to the first dose of study drug
• Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions (including laboratory abnormalities) that could interfere with participant’s safety, obtaining informed consent or compliance to the study procedures
• Evidence of active mucosal or internal bleeding
• Cirrhosis or current unstable liver or biliary disease
• Evidence of cardiovascular risk
• Active infection requiring treatment
• Participants with known human immunodeficiency virus (HIV) infection, Hepatitis B, and cirrhosis
• Current corneal disease except for mild punctate keratopathy
• Intolerance or contraindications to anti-viral prophylaxis Exclusion criteria for DREAMM 7 only:
• Participants Intolerant to daratumumab
• Refractory to daratumumab or any other anti-CD38 therapy
• Ongoing Grade 2 or higher peripheral neuropathy or neuropathic pain
• Prior treatment with anti- B cell maturation antigen (BCMA) therapy
• Prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study drugs, or treatment with an investigational agent or approved systemic antimyeloma therapy (including systemic steroids) within 14 days or 5 half-lives of receiving the first dose of study drugs, whichever is shorter
• Has received radiotherapy to a large pelvic area
• Prior allogenic stem cell transplant
• Any major surgery within 4 weeks prior to the first dose of study drug
• Presence of active renal condition (infection, requirement for dialysis or any other condition that could affect participant’s safety)
• Previous or concurrent malignancies other than multiple myeloma, 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
• Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to belantamab mafodotin, daratumumab, bortezomib, boron or mannitol or any other components of the study treatment
• Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, skin changes) or active plasma cell leukaemia at the time of screening Exclusion criteria for DREAMM 8 study only:
• Received prior treatment with or intolerant to pomalidomide
• Ongoing Grade 2 peripheral neuropathy with pain within 14 days prior to randomization or ≥ Grade 3 peripheral neuropathy
• Received prior BCMA targeted therapy
• Systemic anti-myeloma therapy (including chemotherapy and systemic steroids) or use of an investigational drug within 14 days or five half-lives (whichever is shorter) preceding the first dose of study drug; Prior treatment with an anti-MM monoclonal antibody drug within 30 days of receiving the first dose of study drugs
• Participants after prior allogeneic stem cell treatment (SCT)
• Any major surgery within the last 4 weeks
• Presence of active renal conditions (e.g., infection, severe renal impairment requiring dialysis or any other condition that could affect participant’s safety
• Previous or concurrent invasive malignancy other than multiple myeloma, except: a. The disease must be considered medically stable for at least 2 years; or b. The participant must not be receiving active therapy, other than hormonal therapy for this disease
• Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to belantamab mafodotin or drugs chemically related to belantamab mafodotin, or any of the components of the study treatment
• Japan only: must test HBeAg and HBeAb Eligibility verification should be evaluated and agreed with a hepatologist (after they record the approval in the patient medical record).
• Active plasma cell leukemia at the time of Screening. Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, and skin changes)
• Active or history of venous and arterial thromboembolism within the past 3 months
• Contraindications to or unwilling to undergo protocol-required anti-thrombotic prophylaxis
• Pregnant or lactating female