Sub-study of Belantamab Mafodotin (GSK2857916) in Combination With Isatuximab in Participants With RRMM

Inclusion Criteria:

• Participant must be 18 years of age inclusive or older, at the time of signing theinformed consent.

• Participants must have histologically or cytologically confirmed diagnosis ofMultiple Myeloma (MM), as defined by the IMWG.

• Participants having at least 3 prior lines of prior anti-myeloma treatmentsincluding an immunomodulating agent (IMID) a proteasome inhibitor (PI) and ananti-CD38 monoclonal antibody.

• Participants with a history of autologous stem cell transplant are eligible forstudy participation when, transplant was >100 days prior to study enrolment and withno active infection(s).

• Participants with Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, unless ECOG less than equal to (<=)2 is due solely to skeletal complicationsand/or skeletal pain due to MM.

• Participants with measurable disease defined as at least one of the following: SerumM-protein greater than equal to (>=)0.5 gram per deciliter (>=5 gram per liter) orUrine M-protein >=200 milligrams (mg) per 24 hours or Serum free light chain (FLC)assay: Involved FLC level >=10 mg per deciliter (>=100 mg per Liter) and an abnormalserum FLC ratio (<0.26 or >1.65).

• Participants who have tested positive for Hepatitis B core antibody (HBcAb) can beenrolled if the following criteria are met: Serology result HBcAb+, Hepatitis Bsurface antigen (HBsAg)-; HBV deoxyribonucleic acid (DNA) undetectable duringscreening.

• Participants who are currently receiving physiological doses oral steroids (<10mg/day), inhaled steroids or ophthalmological steroids.

Exclusion Criteria:

• Participants with current corneal epithelial disease except mild punctatekeratopathy.

• Participants with evidence of cardiovascular risk.

• Participants with known immediate or delayed hypersensitivity reaction oridiosyncrasy to drugs chemically related to belantamab mafodotin or any of thecomponents of the study treatment. History of severe hypersensitivity to other mAb.

• Participants with active infection requiring antibiotic, antiviral, or antifungaltreatment.

• Participants with other monoclonal antibodies within 30 days or systemicanti-myeloma therapy within <14 days.

• Participants with prior radiotherapy within 2 weeks of start of study therapy.

• Participants with prior allogeneic transplant are prohibited.

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

• Participants with any major surgery (other than bone-stabilizing surgery) within thelast 30 days.

• Participants with prior treatment with an investigational agent within 14 days or 5half-lives of receiving the first dose of study drugs, whichever is shorter.

• Participants with >=grade 3 toxicity considered related to prior check-pointinhibitors and that led to treatment discontinuation.

• Participants who have received transfusion of blood products within 2 weeks beforethe first dose of study drug.

• Participants must not receive live attenuated vaccines within 30 days prior to firstdose of study treatment or whilst receiving belantamab mafodotin +- partner agent inany sub-study arm of the platform trial and for at least 70 days following laststudy treatment.

• Participants with presence of active renal condition (infection, requirement fordialysis or any other condition that could affect participant's safety).Participants with isolated proteinuria resulting from MM.

• Participants with known human immunodeficiency virus (HIV) infection, unless theparticipant can meet all criteria: a) established anti-retroviral therapy for atleast 4 weeks and HIV viral load<400 copies/milliliter (mL) b) cluster ofdifferentiation 4 plus (CD4+) T-cell (CD4+) counts >= 350 cells/microliter (µL) c)No history of Acquired immunodeficiency syndrome (AIDS)-defining opportunisticinfections within the last 12 months in which case the participant would be eligiblefor CE Phase only. For participants receiving nirogacestat, HIV drugs that arestrong Cytochrome P450 3A4 (CYP3A4) inhibitors are prohibited. HIV drugs that aremoderate CYP3A4 inhibitors, while permitted, should be co-administered with cautionand must be accompanied by nirogacestat dose modifications.

• Participants with Severe hypersensitivity to Isatuximab-irfc or to any of itsexcipients.

• Participants with prior treatment with other anti-CD38 monoclonal antibody within 6months of the first dose of study drug treatment.

• Participants with known intolerance or hypersensitivity to infused proteinsproducts, sucrose, histidine, and polysorbate 80.