- - Provide signed written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form.
- - Male or female, 20 years or older (at the time consent is obtained).
- - ECOG performance status of 0 to 2.
- - Histologically or cytologically confirmed diagnosis of multiple myeloma as defined
according to IMWG 2014, criteria in a participant who fulfills all of the following:
has undergone stem cell transplant, or is considered transplant ineligible, Part 1:
has received at least 2 prior lines of anti-myeloma drugs containing at least 1
proteasome inhibitor and at least 1 immunomodulator, Part 2: has received at least 1
prior line of anti-myeloma drugs; has demonstrated progression on, or within 60 days
of completion of the last therapy.
- - 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 mg/24 hours;
Serum free light chain (FLC) assay: Involved FLC level >=10 mg/dL (>=100 mg/L) 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 enrolment; No active infection.
- - Female participants: Contraceptive use by women should be consistent with local
regulations regarding the methods of contraception for those participating in clinical
A female participant is eligible to participate if she is not pregnant or
breast feeding, and at least one of the following conditions applies: Is not a woman
of childbearing potential (WOCBP) or For Part 1 and Part 2 Arm A: Is a WOCBP and using
a contraceptive method that is highly effective (with a failure rate of <1 percent per
year), preferably with low user dependency, during the treatment period and for 4
months after the last dose of GSK2857916, and 7 months from the last dose of
bortezomib (only Part 2 Arm A), 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
treatment. 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
treatment and agree to use effective contraception during the study and for 4 months
after the last dose of GSK2857916, and 7 months from the last dose of bortezomib (only
Part 2 Arm A); For Part 2 Arm B: Due to pomalidomide being a thalidomide analogue with
risk for embryo-fetal toxicity and prescribed under a restricted distribution program,
WOCBP participants will be eligible if they commit either to abstain continuously from
heterosexual sexual intercourse or to use 2 methods of reliable birth control,
beginning 4 weeks prior to initiating treatment with pomalidomide, during therapy,
during dose interruptions and continuing for 4 weeks following discontinuation of
pomalidomide treatment. Thereafter, WOCBP participants must use a contraceptive method
that is highly effective (with a failure rate of <1 percent per year) for a further 3
months, and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction
during this period. Two negative pregnancy tests must be obtained prior to initiating
pomalidomide therapy. The first test should be performed within 10 to 14 days and the
second test within 24 hours prior to prescribing pomalidomide therapy. 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
- - Male participants: Contraceptive use by men should be consistent with local
regulations regarding the methods of contraception for those participating in clinical
Male participants are eligible to participate if they agree to the following
from the time of first dose of study treatment until 6 months after the last dose of
GSK2857916, 4 months after the last dose of bortezomib (only Part 2 Arm A), and 4
weeks after the last dose of pomalidomide (only Part 2 Arm B) to allow for clearance
of any altered sperm: Refrain from donating sperm plus either: 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 must agree to use
contraception/barrier as detailed: Agree to use a male condom even if they have
undergone a successful vasectomy 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 (including 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.
Participants with Grade 2 peripheral
neuropathy can be enrolled into Part 1 and Part 2 Arm B but not into Part 2 Arm A.
- - Adequate Organ System Function.
- - Systemic anti-tumor-therapy within 14 days, or plasmapheresis within 7 days prior to
the first dose of study treatment.
- - Symptomatic amyloidosis, active 'polyneuropathy, organomegaly, endocrinopathy, myeloma
protein, and skin changes' (POEMS) syndrome, active plasma cell leukemia at the time
- - Use of an investigational drug within 14 days or 5 half-lives, whichever is shorter,
preceding the first dose of study treatment.
Prior treatment with a monoclonal
antibody within 30 days of receiving the first dose of study treatment. Prior BCMA
- - History of an allogeneic stem cell transplant.
- - Current use of prohibited medications/device or planned use of any of these during the
- - Current corneal epithelial disease except mild punctate keratopathy.
- - 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 multiple myeloma are eligible, provided they fulfil the
- - Evidence of active mucosal or internal bleeding.
- - Any major surgery within the last 4 weeks.
- - 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
- - Active infection requiring treatment (antibiotic, antiviral, or antifungal treatment).
- - Evidence of severe or uncontrolled systemic diseases.
- - 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 investigators and Medical Monitor, will not affect the
evaluation of the effects of this clinical study treatment on the currently targeted
malignancy (multiple myeloma).
- - Evidence of cardiovascular risk including any of the following:
Corrected QT interval Fridericia (QTcF) interval >=470 milliseconds (msecs) (the
QT interval values must be corrected for heart rate by Fridericia's formula
2. Evidence of current clinically significant uncontrolled arrhythmias, including
clinically significant ECG abnormalities such as 2nd degree (Type II) or 3rd
degree atrioventricular (AV) block.
3. History of myocardial infarction, acute coronary syndromes (including unstable
angina), coronary angioplasty, or stenting or bypass grafting within 6 months of
4. Class III or IV heart failure as defined by the New York Heart Association
functional classification system. 5. 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 or female who are interrupting lactation.
- - Known human Immunodeficiency virus (HIV) infection.
- - Presence of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb)
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
Participants with positive hepatitis C antibody due to prior resolved
disease can only be enrolled, if a confirmatory negative hepatitis C RNA test is
obtained. Hepatitis RNA testing is optional and participants with negative hepatitis C
antibody test are not required to also undergo hepatitis C RNA testing.
- - 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 participant otherwise meets entry criteria.
- - Previously diagnosed with interstitial lung disease or current complication of
interstitial lung disease.
Additional Exclusion Criteria for Part 2 Arm A.
- - Intolerant to bortezomib or refractory to bortezomib.
- - Ongoing Grade 2 or higher peripheral neuropathy or neuropathic pain.
- - Intolerance or contraindications to herpes zoster prophylaxis Additional Exclusion
Criteria for Part 2 Arm B.
- - Prior pomalidomide use.
- - Intolerance or contraindications to antithrombotic prophylaxis.
- - Active or history of venous thromboembolism within 3 months prior to first dose of