A Study to Investigate the Efficacy and Safety of Two Doses of GSK2857916 in Participants With Multiple Myeloma Who Have Failed Prior Treatment With an Anti-CD38 Antibody
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Belantamab mafodotin frozen liquid; Belantamab mafodotin lyophilized powder
Intervention description: Belantamab mafodotin will be available as frozen liquid. Frozen liquid will be available as 30 milligram (mg)/vial solution in a single use vial with unit dose strength of 2.5 or 3.4 mg/kg. Belantamab mafodotin will be administered as IV solution over at least 30 minutes. Frozen belantamab mafodotin will be diluted in 0.9 percent saline and administered via infusion pump.; Belantamab mafodotin will be available as lyophilized powder. Lyophilized powder will be available as 100 mg/vial in single-use vial for reconstitution with unit dose strength of 3.4 mg/kg. Lyophilized belantamab mafodotin will be reconstituted using water for injection and diluted with saline before use.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 221.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Relapsed Refractory multiple myeloma; Antibody-drug conjugate; Patient-Reported Outcome Version of the Common Term Criteria for Adverse Events; Quality of Life Questionnaire 20-item Multiple Myeloma module; Multiple Myeloma; Quality of Life Questionnaire 30-item Core module

Summary:

      Multiple myeloma (MM) is an incurable malignancy and accounts for 1 percentage (%) of all
      cancers and for 10% of all hematologic malignancies. Participants with relapsed/refractory
      multiple myeloma (RRMM) will be included in this study, to evaluate the efficacy and safety
      of belantamab mafodotin (GSK2857916) monotherapy. Participants will be treated with
      belantamab mafodotin monotherapy until disease progression (PD) or unacceptable toxicity and
      will be followed for Progression Free Survival and Overall survival. The participants will be
      randomized to receive either frozen belantamab mafodotin at the dose of 2.5 milligram per
      kilogram (mg/kg) or 3.4 mg/kg administered Intravenously (IV). There will be an independent
      cohort of participants who will receive a lyophilized configuration of belantamab mafodotin.
      For participants who discontinued from the study other than Progressive disease (PD), disease
      evaluation will continue to be performed at 3-week intervals until confirmed PD, death, start
      of a new anticancer treatment, withdrawal of consent, or end of the study whichever occurs
      first.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants who provided signed written informed consent, which includes compliance
             with the requirements and restrictions listed in the consent form.

          -  Male or female, 18 years or older.

          -  Participants with Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

          -  Participants with histologically or cytologically confirmed diagnosis of MM as defined
             in IMWG, 2014 criteria, and participant has undergone stem cell transplant or is
             considered transplant ineligible and has failed at least 3 prior lines of anti-myeloma
             treatments, including an anti-CD38 antibody (example [e.g.], daratumumab) alone or in
             combination, and is refractory to an Immunomodulatory drug (IMiD) (that is [i.e.],
             lenalidomide or pomalidomide), and to a proteasome inhibitor (e.g., bortezomib,
             ixazomib or carfilzomib).

          -  The participant has measurable disease with at least one of the following: Serum
             M-protein >=0.5 grams per deciliter (g/dL) (>=5 grams per Liter [g/L]); Urine
             M-protein >=200 milligram per 24 hours (mg/24h); Serum Free light chain (FLC) assay:
             Involved FLC level >=10 mg/dL (>=100 mg/Liter) and an abnormal serum FLC ratio (<0.26
             or >1.65).

          -  Participants with a history of autologous stem cell transplant are eligible for study
             participation provided the following eligibility criteria are met: transplant was >100
             days prior to study enrollment; no active infection(s); participants meet the
             remainder of the eligibility criteria outlined in the protocol.

          -  Participants with adequate organ system functions as defined follows: Absolute
             neutrophil count (ANC) >=1.0 X 10^9/L; Hemoglobin >=8.0 g/dL; Platelets>= 50 X 10^9/L;
             Total bilirubin <=1.5X Upper limit of normal (ULN). Isolated bilirubin >=1.5xULN is
             acceptable if bilirubin is fractionated and direct bilirubin <35 percent); Alanine
             aminotransferase (ALT) <=2.5X ULN; Estimated glomerular filtration rate (eGFR) >=30
             milliliter per minute per 1.73 meter square (mL/min/m^2); Spot urine
             (albumin/creatinine ratios [spot urine]) <500 milligram per gram (mg/g) (56 mg per
             millimoles [mg/mmol]); Left ventricular ejection fraction (LVEF) (Echocardiogram)>=45
             percent.

          -  Female participants: Contraceptive use by men or women should be consistent with local
             regulations regarding the methods of contraception for those participating in clinical
             studies. A female participant is eligible to participate if she is not pregnant or
             breastfeeding, and not a woman of childbearing potential (WOCBP) or is a WOCBP and
             using a contraceptive method that is highly effective (with a failure rate of <1% per
             year), preferably with low user dependency, during the intervention period and for at
             least 80 days after the last dose of study intervention and agrees not to donate eggs
             (ova, oocytes) for the purpose of reproduction during this period. The investigator
             should evaluate the effectiveness of the contraceptive method in relationship to the
             first dose of study intervention. A WOCBP must have a negative highly sensitive serum
             pregnancy test (as required by local regulations) within 72 hours before the first
             dose of study intervention. The investigator is responsible for review of medical
             history, menstrual history, and recent sexual activity to decrease the risk for
             inclusion of a woman with an early undetected pregnancy.

          -  Male participants: Contraceptive use by men or women should be consistent with local
             regulations regarding the methods of contraception for those participating in clinical
             studies. Male participants are eligible to participate if they agree to the following
             during the intervention period and for at least 140 days: Refrain from donating sperm;
             Be abstinent from heterosexual intercourse as their preferred and usual lifestyle
             (abstinent on a long term and persistent basis) and agree to remain abstinent; or
             Agree to use a male condom and female partner to use an additional highly effective
             contraceptive method with a failure rate of <1% per year as when having sexual
             intercourse with a WOCBP who is not currently pregnant.

          -  All prior treatment-related toxicities (defined by National Cancer Institute- Common
             Toxicity Criteria for Adverse Events [NCI-CTCAE]), version 4.03, must be <=Grade 1 at
             the time of enrollment except for alopecia and Grade 2 peripheral neuropathy.

          -  For France only: A participant will be eligible for inclusion in this study only if
             either affiliated to or a beneficiary of a social security category.

        Exclusion Criteria:

          -  Systemic anti-myeloma therapy within <=14 days, or 5 half-lives, whichever is shorter,
             or plasmapheresis within 7 days prior to the first dose of study drug.

          -  Systemic treatment with high dose steroids (equivalent to >=60 mg prednisone daily for
             >=4 days) within the past 14 days if administered to treat MM or non-MM disease.

          -  Symptomatic amyloidosis, active 'polyneuropathy, organomegaly, endocrinopathy, myeloma
             protein, and skin changes' (POEMS) syndrome, active plasma cell leukemia at the time
             of screening.

          -  Prior allogeneic stem cell transplant.

          -  Current corneal epithelial disease except mild punctate keratopathy.

          -  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 a monoclonal
             antibody within 30 days of receiving the first dose of study drugs. Prior B-cell
             maturation antigen (BCMA) targeted therapy.

          -  Evidence of active mucosal or internal bleeding.

          -  Any major surgery within the last four weeks.

          -  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.

          -  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 to the study procedures.

          -  Current unstable liver or biliary disease per investigator assessment defined by the
             presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or
             gastric varices, persistent jaundice, or cirrhosis.

          -  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 investigators and GlaxoSmithKline Medical Monitor,
             will not affect the evaluation of the effects of this clinical trial treatment on the
             currently targeted malignancy (MM). Participants with curatively treated non-melanoma
             skin cancer may be enrolled.

          -  Evidence of cardiovascular risk including any of the following: Corrected QT interval
             Fridericia (QTcF) interval >480 milliseconds (msec); Evidence of current clinically
             significant uncontrolled arrhythmias, including clinically significant
             electrocardiogram abnormalities such as 2nd degree (Type II) or 3rd degree
             atrioventricular (AV) block; History of myocardial infarction, acute coronary
             syndromes (including unstable angina), coronary angioplasty, or stenting or bypass
             grafting within six months of Screening; Class III or IV heart failure as defined by
             the New York Heart Association functional classification system (NYHA); Uncontrolled
             hypertension.

          -  Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
             chemically related to belantamab mafodotin, or any of the components of the study
             treatment.

          -  Pregnant or lactating female.

          -  Active infection requiring antibiotic, antiviral, or antifungal treatment.

          -  Known Human Immunodeficiency Virus (HIV) infection.

          -  Presence of hepatitis B surface antigen (HBsAg), or hepatitis B core antibody (HBcAb
             at screening or within 3 months prior to first dose of study treatment.

          -  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 study
             treatment.