- Subjects provide signed written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form.
- Male or female, 18 years or older.
- Subjects with Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Histologically or cytologically confirmed diagnosis of MM as defined according to
International Myeloma Working Group (IMWG). The subject 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 drugs
(IMiD) (that is [i.e.], lenalidomide or pomalidomide), and to a proteasome inhibitor
(i.e., bortezomib, ixazomib or carfilzomib).
- The subject has measurable disease with at least one of the following: Serum M-protein
>=0.5 gram per deciliter (g/dL) (>=5 gram 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/L) and an abnormal serum free light chain ratio (<0.26 or
- Subjects 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 enrolment; no active infection(s); subjects meets the remainder of
the eligibility criteria outlined in this protocol.
- Subjects 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) >= 45 percent.
- Female subjects: 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 subject 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.
- Male subjects 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; Agree
to use a male condom and female partner to use an additional highly effective
contraceptive method with a failure rate of <1 percent per year as when having sexual
intercourse with a woman of childbearing potential 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 enrolment except for alopecia and Grade 2 peripheral neuropathy.
- For France only: A subject will be eligible for inclusion in this study only if either
affiliated to or a beneficiary of a social security category.
- Systemic anti-myeloma therapy within <14 days, or plasmapheresis within 7 days prior
to the first dose of study drug.
- Symptomatic amyloidosis, active 'polyneuropathy, organomegaly, endocrinopathy, myeloma
protein, and skin changes' (POEMS) syndrome, active plasma cell leukemia at the time
- 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 BCMA
- 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 subject's safety). Subjects 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. Stable chronic liver disease
(including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement
of malignancy is acceptable if subject otherwise meets entry criteria.
- Malignancies other than disease under study are excluded, except for any other
malignancy from which the subject has been disease-free for more than 2 years and, in
the opinion of the principal investigators and GSK Medical Monitor, will not affect
the evaluation of the effects of this clinical trial treatment on the currently
targeted malignancy (MM).
- Evidence of cardiovascular risk including any of the following: Corrected QT interval
Fridericia (QTcF) interval >=470 milliseconds (msecs); Evidence of current clinically
significant uncontrolled arrhythmias, including clinically significant ECG
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 GSK2857916, 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. Subjects with positive Hepatitis C antibody due to prior resolved disease
can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained.