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Multiple MyelomaPhase 1NCT02064387

Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Clinical Activity of GSK2857916

A Phase 1 study testing GSK2857916 in people with Multiple Myeloma, run by GlaxoSmithKline at 9 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study will assess the safety, pharmacokinetic (PK), pharmacodynamic (PD) and the therapeutic potential of GSK2857916 in subjects with multiple myeloma (MM) and lymphomas that express B cell maturation antigen (BCMA). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
GSK2857916
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
79 participants
Where
9 sitesin 3 countries
Study dates
29 Jul 2014to 1 Aug 2019
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 (at the time consent is obtained)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Part 1/dose escalation; Histologically or cytologically confirmed diagnosis of Multiple Myeloma in a subject who fulfills all of the following: has undergone stem cell transplant, or is considered transplant ineligible, has been pretreated with at least the 3 following classes of anti-myeloma drugs: alkylators, proteasome inhibitors and immunomodulators, has demonstrated progression on, or within 60 days of completion of the last therapy.
  • Part 2 /MM cohort; Histologically or cytologically confirmed diagnosis of: Multiple Myeloma in a subject who fulfills all of the following: has undergone stem cell transplant, or is considered transplant ineligible, has been pretreated with at least the 3 following classes of anti-myeloma drugs: alkylators, proteasome inhibitors and immunomodulators, has demonstrated progression on, or within 60 days of completion of the last therapy, and has measurable disease with at least one of the following: serum M-protein >=0.5 gram (g)/decilitre (dL) (>=5 g/Litre (L)), urine M-protein >=200 milligram (mg)/24hour (h).
  • Serum free light chain (FLC) assay: Involved FLC level >=5 mg/dL (>=50 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65) and biopsy proven plasmacytoma (should be measured within 28 days of Screening Visit).
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  • Part 2/Other BCMA positive Hematologic Malignancies cohort: Subject with one of the following lymphomas: Diffuse Large B-cell Lymphoma (DLBCL) or follicular lymphoma (FL) that exhibits positive BCMA expression on tumor cells as determined by a central laboratory using a validated Immunohistochemistry (IHC) assay. Eligible subjects with BCMA positive malignancies must also fulfill the prior treatment requirements as follows: DLBCL: at least 2 prior lines of systemic therapy containing at least one line of chemo-immunotherapy with anti-CD20 antibody, and either has undergone stem cell transplant or is considered transplant ineligible. FL: at least 2 prior lines of systemic therapy.
  • 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; subject meets the remainder of the eligibility criteria outlined in the study protocol.
  • Adequate organ system functions as defined below Absolute neutrophil count>=1.0x10^9/L, hemoglobin>=8.0 g/dL, platelet>=50x10^9/L, international normalized ration (INR) <=1.5, Partial thromboplastin time <=1.5xupper limit of normal (ULN), total bilirubin <=1.25xULN, alanine aminotransferase and aspartate aminotransferase<=1.5 X ULN, serum creatinine or calculated creatinine clearance<1.2XULN >=60 mL/min for Part 1;>=50 mL/minute (min) for Part 2 if data supports loosening criteria, Albuminuria<=500 mg/24h, left ventricular ejection fraction >=50%, Troponin<=1xULN, Calcium<=1.1xULN
  • A female subject is eligible to participate if she is of: Non-childbearing potential or women of childbearing potential must have a negative serum pregnancy test within 72 hours of first dose of study treatment and agree to use effective contraception during the study and for 60 days following the last dose of study treatment.
  • Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception from the time of first dose of study until 60 days after the last dose of study treatment to allow for clearance of any altered sperm
  • All prior treatment-related toxicities (defined by National Cancer Institute- Common Toxicity Criteria for Adverse Events, version 4) must be <=Grade 1 at the time of enrollment except for alopecia, and grade 2 neuropathy.

Who cannot join

  • Systemic anti-tumor therapy within 14 days, or plasmapheresis within 7 days prior to the first dose of study drug
  • 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 drug.
  • History of an allogeneic stem cell transplant. Subjects with a history of an autologous stem cell transplant are NOT excluded if they meet inclusion criteria related to history of autologous stem cell transplant.
  • 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, provided they fulfil the inclusion criteria related to organ system function.
  • Evidence of active mucosal or internal bleeding
  • Any major surgery within the last four weeks.
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  • Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions (including lab abnormalities) that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures.
  • Known active infection requiring antibiotic treatment
  • Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, hepatic, renal or cardiac disease
  • Subjects with previous or concurrent malignancies are allowed only if the second tumor is not contributing to the subject's illness. The subject must not be receiving active therapy, other than hormonal therapy for this disease and the disease must be considered medically stable for at least 2 years.
  • Evidence of cardiovascular risk including any of the following: QT interval corrected>=470 millisecond, evidence of current clinically significant uncontrolled arrhythmias, 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, uncontrolled hypertension, subjects with intra-cardiac defibrillators or permanent pacemakers, abnormal cardiac valve morphology (>=grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study). Subjects with moderate valvular thickening should not be entered on study.
  • 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.
  • Known human immuno virus infection.
  • Subjects with positive test for Hepatitis B surface (HBS-Ag) or Hepatitis B core (HBc)antigen
  • Subjects with positive test for hepatitis C (HCV) infection are excluded regardless of viral load. If hepatitis C antibody test is positive, a confirmatory polymerase chain reaction (PCR) or Recombinant immunoblot assay (RIBA) test should be performed. If the PCR or RIBA test is negative, subject is eligible for this trial
  • Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per investigator's assessment).
  • Current corneal disease or a history of corneal disease.

Trial locations and contacts

9 sites in 3 countries.

9 sites in 3 countries

United States6 sites

  • GSK Investigational Site

    Boston, Massachusetts, 02215

  • GSK Investigational Site

    Chapel Hill, North Carolina, 27599-7600

  • GSK Investigational Site

    Dallas, Texas, 75390-8565

  • GSK Investigational Site

    New York, New York, 10065

  • GSK Investigational Site

    Philadelphia, Pennsylvania, 19104

  • GSK Investigational Site

    Seattle, Washington, 98109

Other trials in United States

Canada2 sites

  • GSK Investigational Site

    Toronto, Ontario, M5G 2M9

  • GSK Investigational Site

    Vancouver, British Columbia, V5Z 1M9

Other trials in Canada

United Kingdom1 site

  • GSK Investigational Site

    London, NW1 2BU

Other trials in United Kingdom

About this study

Official title: A Phase I Open-label, Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Clinical Activity of the Antibody Drug Conjugate GSK2857916 in Subjects With Relapsed/Refractory Multiple Myeloma and Other Advanced Hematologic Malignancies Expressing BCMA

This study will assess the safety, pharmacokinetic (PK), pharmacodynamic (PD) and the therapeutic potential of GSK2857916 in subjects with multiple myeloma (MM) and lymphomas that express B cell maturation antigen (BCMA). The hypothesis is that GSK2857916 can be safely administered to subjects with MM and with BCMA positive malignancies at doses where target engagement can be demonstrated. This study will determine if adequate target engagement of BCMA receptors translates into clinical benefit for subjects with MM and BCMA positive lymphomas. The study will consists of two parts: a Part 1 dose escalation phase and a Part 2 expansion phase for safety, tolerability, PK, PD, and clinical activity testing. The study will enroll a total of approximately 80-95 subjects with relapsed/refractory MM or BCMA-expressing hematologic malignancies. The maximum dose to be administered in this trial will not exceed 5 milligram/kilogram(mg/kg).

Being tested
GSK2857916
Keywords
Multiple Myeloma, BCMA expressing Lymphomas
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GSK2857916Drug

    A clear or opalescent solution for IV infusion with unit dose strength of 20 mg/mililiter (mL) for multiple dose levels.

Study groups in NCT02064387
Study groupRoleWhat they receive
Schedule 1 Part 1ExperimentalParticipants will receive GSK2857916 intravenously over 60 minutes (one dose) every 3 weeks (21 day cycle) for a maximum of 16 cycles.
Receives: Drug: GSK2857916
Schedule 2 Part 1ExperimentalParticipants may receive GSK2857916 intravenously over 60 minutes (one dose) once weekly for three consecutive weeks followed by 1 week of rest (28 day cycle) for a maximum of 16 cycles.
Receives: Drug: GSK2857916
Schedule 1 Part 2ExperimentalParticipants will receive the dose and schedule of GSK2857916 evaluated in Part 1 that is selected for further evaluation in Part 2 for up to 16 cycles.
Receives: Drug: GSK2857916
Schedule 2 Part 2ExperimentalParticipants may receive the dose and schedule of GSK2857916 evaluated in Part 1 that is selected for further evaluation in Part 2 for a maximum of 16 cycles.
Receives: Drug: GSK2857916

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Serious Adverse Events (SAEs) and Common (>=5%) Non-serious Adverse Events- Part 1

    An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, other medical events according to medical or scientific judgement and all events of possible study treatment-induced liver injury with hyperbilirubinemia. Part 1 Population comprised of all Part 1 participants (exclusively MM) who received at least one dose of GSK2857916. SAEs and common (>=5%) non-SAEs is presented.

    Measured: Up to 23.5 months (maximum duration of follow-up from first dose to last contact or death)

  2. Number of Participants With SAEs and Common (>=5%) Non-serious Adverse Events- Part 2 (MM)

    An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, other medical events according to medical or scientific judgement and all events of possible study treatment-induced liver injury with hyperbilirubinemia. Part 2 MM Population comprised of all Part 2 MM participants who received at least one dose of GSK2857916. SAEs and common (>=5%) non-SAEs is presented.

    Measured: Up to 35 months (maximum duration of follow-up from first dose to last contact or death)

  3. Number of Participants With SAEs and Common (>=5%) Non-serious Adverse Events- Part 2 (NHL)

    An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, other medical events according to medical or scientific judgement and all events of possible study treatment-induced liver injury with hyperbilirubinemia. Part 2 NHL Population comprised of all Part 2 NHL participants who received at least one dose of GSK2857916. SAEs and common (>=5%) non-SAEs is presented.

    Measured: Up to 7.2 months (maximum duration of follow-up from first dose to last contact or death)

  4. Number of Participants With Dose-limiting Toxicities (DLTs) During the Determinative Period- Part 1

    An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of the following criteria:albuminuria>=2000mgper24 hour which has been confirmed by repeat test at least7 days apart and is not considered to be related to disease progression, Grade4 neutropenia (without fever) lasting>=7 days, febrile neutropenia lasting>=72 hours, Grade>=3 thrombocytopenia associated with bleeding where estimated blood loss is>10 milliliter orGrade4 thrombocytopenia lasting>7 days and not responding to platelet transfusions, anyGrade3 or greaternon-hematologic toxicity as described in Common National Cancer Institute-Terminology Criteria for Adverse Events version4.0 with the exception of the following Grade3 events that can be controlled within48 hours with routine supportive measures and clinically asymptomatic electrolyte abnormalities which can be corrected within48 hours and liver toxicity meeting pre-specified GSK liver stopping criteria.

    Measured: Up to Day 21 (from first dose)

  5. Number of Participants With Grade Change From Baseline in Vital Signs-DBP & SBP-Part 1

    Vital signs included systolic blood pressure (SBP), diastolic blood pressure (DBP), temperature (Temp) and heart rate (HR). SBP and DBP were graded using National Cancer Institute-Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0. For SBP: Grade 0-<120 millimeters of mercury[mmHg], 120-139 mmHg[Grade 1], 140-159 mmHg[Grade 2], >=160 mmHg[Grade 3]); For DBP: <80 mmHg [Grade 0], 80-89[Grade 1], 90-99[Grade 2], >=100 mmHg[Grade 3]). An increase is defined as an increase in CTCAE grade relative to Baseline grade. Baseline was defined as the latest pre-dose assessment with a non-missing value, including unscheduled visits. Data for worst-case post Baseline is presented.

    Measured: Baseline and Up to 21.6 months (maximum duration of follow-up from first dose to last contact or death)

  6. Number of Participants With Grade Change From Baseline in Vital Signs-DBP & SBP-Part 2 (MM)

    Vital signs included SBP, DBP, Temp and HR. SBP and DBP were graded using NCI CTCAE version 4.0. For SBP: Grade 0-<120 mmHg, 120-139 mmHg[Grade 1], 140-159 mmHg[Grade 2], >=160 mmHg[Grade 3]); For DBP: <80 mmHg [Grade 0], 80-89[Grade 1], 90-99[Grade 2], >=100 mmHg[Grade 3]). An increase is defined as an increase in CTCAE grade relative to Baseline grade. Baseline was defined as the latest pre-dose assessment with a non-missing value, including unscheduled visits. Data for worst-case post Baseline is presented.

    Measured: Baseline and Up to 24.2 months (maximum duration of follow-up from first dose to last contact or death)

  7. Number of Participants With Grade Change From Baseline in Vital Signs-DBP & SBP-Part 2 (NHL)

    Vital signs included SBP, DBP, Temp and HR. SBP and DBP were graded using NCI CTCAE version 4.0. For SBP: Grade 0-<120 mmHg, 120-139 mmHg [Grade 1], 140-159 mmHg[Grade 2], >=160 mmHg [Grade 3]); For DBP: <80 mmHg [Grade 0], 80-89[Grade 1], 90-99[Grade 2], >=100 mmHg[Grade 3]). An increase is defined as an increase in CTCAE grade relative to Baseline grade. Baseline was defined as the latest pre-dose assessment with a non-missing value, including unscheduled visits. Data for worst-case post Baseline is presented.

    Measured: Up to 7.2 months (maximum duration of follow-up from first dose to last contact or death)

  8. Number of Participants With Change From Baseline in Heart Rate and Temperature-Part 1

    The following criteria was used to flag vital signs of potential clinical importance: change from Baseline in heart rate (decrease to <60 beats per minute [bpm] and increase to >100 bpm) and change in temperature from Baseline (increase to >=38 or decrease to <=35 degrees celsius). Baseline was defined as the latest pre-dose assessment with a non-missing value, including unscheduled visits. Data for worst-case post Baseline is presented.

    Measured: Baseline and Up to 21.6 months (maximum duration of follow-up from first dose to last contact or death)

  9. Number of Participants With Change From Baseline in Heart Rate and Temperature-Part 2 (MM)

    The following criteria was used to flag vital signs of potential clinical importance: change from Baseline in heart rate (decrease to <60 bpm and increase to >100 bpm) and change in temperature from Baseline(increase to >=38 or decrease to <=35 degrees celsius). Baseline was defined as the latest pre-dose assessment with a non-missing value, including unscheduled visits. Data for worst-case post Baseline is presented.

    Measured: Baseline and Up to 24.2 months (maximum duration of follow-up from first dose to last contact or death)

  10. Number of Participants With Change From Baseline in Heart Rate and Temperature-Part 2 (NHL)

    The following criteria was used to flag vital signs of potential clinical importance: change from Baseline in heart rate (decrease to <60 bpm and increase to >100 bpm) and change in temperature from Baseline(increase to >=38 or decrease to <=35 degrees celsius). Baseline was defined as the latest pre-dose assessment with a non-missing value, including unscheduled visits. Data for worst-case post Baseline is presented.

    Measured: Baseline and Up to 7.2 months (maximum duration of follow-up from first dose to last contact or death)

  11. Number of Participants With Grade Change From Baseline in Clinical Chemistry Data-Part 1

    Blood samples were collected for the analysis of following clinical chemistry parameters: albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (T.Bil.), calcium (Ca), creatinine (Creat), creatinine kinase (CK), gamma glutamyl transferase (GGT), glucose (Gl), potassium (Pot), magnesium (Mg), sodium (Sod), phosphate (Ph) and urate. Values(Hyper and hypo)for Gl, Pot, Mg, Sod and Ca is presented. Laboratory parameters were graded according to NCI-CTCAE version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences; Grade 5: death related to AE. All increases are an increase in grade from Baseline. Baseline was the latest pre-dose assessment with a non-missing value, including unscheduled visits. Data for worst-case post Baseline is presented.

    Measured: Baseline and Up to 21.6 months (maximum duration of follow-up from first dose to last contact or death)

  12. Number of Participants With Grade Change From Baseline in Clinical Chemistry Data-Part 2 (MM)

    Blood samples were collected for the analysis of following clinical chemistry parameters: albumin,ALP,ALT,AST,T.Bil.,Ca, Creat,CK, GGT,Gl, Pot,Mg, Sod, Ph and urate. Values(Hyper and hypo)for Gl, Pot, Mg, Sod and Ca is presented. Laboratory parameters were graded according to NCI-CTCAE version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences; Grade 5: death related to AE. All increases are an increase in grade from Baseline. Baseline was the latest pre-dose assessment with a non-missing value, including unscheduled visits. Data for worst-case post Baseline is presented.

    Measured: Baseline and Up to 24.2 months (maximum duration of follow-up from first dose to last contact or death)

  13. Number of Participants With Grade Change From Baseline in Clinical Chemistry Data-Part 2 (NHL)

    Blood samples were collected for the analysis of following clinical chemistry parameters: albumin, ALP, ALT, AST, Bilirubin, Ca, Creat, CK, GGT, Glucose, Pot, Mg, Sod, and Ph. Values(Hyper and hypo)for Glucose, Pot, Mg, Sod and Ca is presented. Laboratory parameters were graded according to NCI-CTCAE version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences; Grade 5: death related to AE. All increases are an increase in grade from Baseline. Baseline was the latest pre-dose assessment with a non-missing value, including unscheduled visits. Data for worst-case post Baseline is presented.

    Measured: Baseline and Up to 7.2 months (maximum duration of follow-up from first dose to last contact or death)

  14. Number of Participants With Change From Baseline in Clinical Chemistry Data With Respect to Normal Range-Part 1

    Blood samples were collected for the analysis of following clinical chemistry parameters: direct bilirubin (D.Bil.), chloride, carbon dioxide (CO2), lactate dehydrogenase (LDH), total protein (T.Pro) and urea or blood urea nitrogen (BUN). Baseline was defined as latest pre-dose assessment with a non-missing value, including unscheduled visits. A laboratory value that is outside the reference range was considered either high abnormal (value above the upper limit of the reference range) or low abnormal (value below the lower limit of the reference range). If values were unchanged (example: High to High), or whose value became normal, were recorded in the 'To Normal or No Change (NC)' category. Participants were counted twice if the participant "Decreased to low" and "Increased to high" during post-Baseline. Data for worst-case post Baseline is presented.

    Measured: Baseline and Up to 21.6 months (maximum duration of follow-up from first dose to last contact or death)

  15. Number of Participants With Change From Baseline in Clinical Chemistry Data With Respect to Normal Range-Part 2 (MM)

    Blood samples were collected for the analysis of following clinical chemistry parameters: D.Bil., chloride, CO2, LDH, T.Pro and BUN. Baseline was defined as latest pre-dose assessment with a non-missing value, including unscheduled visits.A laboratory value that is outside the reference range was considered either high abnormal (value above the upper limit of the reference range) or low abnormal (value below the lower limit of the reference range). If values were unchanged (example: High to High), or whose value became normal, were recorded in the 'To Normal or NC' category. Participants were counted twice if the participant 'Decreased to Low' and 'Increased to High' during post-Baseline.Data for worst-case post Baseline is presented.

    Measured: Baseline and Up to 24.2 months (maximum duration of follow-up from first dose to last contact or death)

  16. Number of Participants With Change From Baseline in Clinical Chemistry Data With Respect to Normal Range-Part 2 (NHL)

    Blood samples were collected for the analysis of following clinical chemistry parameters: D.Bil., chloride, CO2, LDH, and T.Pro. Baseline was defined as latest pre-dose assessment with a non-missing value, including unscheduled visits.A laboratory value that is outside the reference range was considered either high abnormal (value above the upper limit of the reference range) or low abnormal (value below the lower limit of the reference range). If values were unchanged (example: High to High), or whose value became normal, were recorded in the 'To Normal or NC' category. Participants were counted twice if the participant 'Decreased to Low' and 'Increased to High' during post-Baseline. Data for worst-case post Baseline is presented.

    Measured: Baseline and Up to 7.2 months (maximum duration of follow-up from first dose to last contact or death)

  17. Number of Participants With Grade Change From Baseline in Hematology Data-Part 1

    Blood samples were collected for the analysis of following hematology parameters: hemoglobin (Hb), lymphocytes (Lymph), neutrophils (Neutro), platelet count (PC), and leukocytes (leuko). The laboratory parameters were graded according to NCI-CTCAE version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences; Grade 5: death related to AE. Baseline was defined as latest pre-dose assessment with a non-missing value, including unscheduled visits. An increase is defined as an increase in CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented.

    Measured: Baseline and Up to 21.6 months (maximum duration of follow-up from first dose to last contact or death)

  18. Number of Participants With Grade Change From Baseline in Hematology Data-Part 2 (MM)

    Blood samples were collected for the analysis of following hematology parameters: Hb, Lymph, Neutro, PC, and leuko. The laboratory parameters were graded according to NCI-CTCAE version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences; Grade 5: death related to AE. Baseline was defined as the latest pre-dose assessment with a non-missing value, including unscheduled visits.An increase is defined as an increase in CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented.

    Measured: Baseline and Up to 24.2 months (maximum duration of follow-up from first dose to last contact or death)

  19. Number of Participants With Grade Change From Baseline in Hematology Data-Part 2 (NHL)

    Blood samples were collected for the analysis of following hematology parameters: Hb, Lymph, Neutro, PC, and leuko. The laboratory parameters were graded according to NCI-CTCAE version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences; Grade 5: death related to AE. Baseline was defined as the latest pre-dose assessment with a non-missing value, including unscheduled visits. An increase is defined as an increase in CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented.

    Measured: Baseline and Up to 7.2 months (maximum duration of follow-up from first dose to last contact or death)

  20. Number of Participants With Change From Baseline in Hematology Data With Respect to Normal Range-Part 1

    Blood samples were collected for the analysis of following hematology parameters: basophils (Baso), eosinophils (Eosino), hematocrit (Hct), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), monocytes (Mono), erythrocytes (Erythro) and reticulocytes (Reticu). A laboratory value that was outside the reference range was considered either high abnormal (value above the upper limit of the reference range) or low abnormal (value below the lower limit of the reference range). Baseline was defined as latest pre-dose assessment with a non-missing value, including unscheduled visits. If values were unchanged (example: High to High), or whose value became normal, were recorded in the 'To Normal or NC' category. Participants were counted twice if the participant 'Decreased to Low' and 'Increased to High' during post-Baseline.Data at worst-case post Baseline is presented.

    Measured: Baseline and Up to 21.6 months (maximum duration of follow-up from first dose to last contact or death)

  21. Number of Participants With Change From Baseline in Hematology Data With Respect to Normal Range-Part 2 (MM)

    Blood samples were collected for the analysis of following hematology parameters: Baso, Eosino, Hct, MCHC, MCH, MCV, Mono, Erythro and Reticu. A laboratory value that was outside the reference range was considered either high abnormal (value above the upper limit of the reference range) or low abnormal (value below the lower limit of the reference range). Baseline was defined as latest pre-dose assessment with a non-missing value, including unscheduled visits. If values were unchanged (example: High to High), or whose value became normal, were recorded in the 'To Normal or NC' category. Participants were counted twice if the participant 'Decreased to Low' and 'Increased to High' during post-Baseline.Data at worst-case post Baseline is presented.

    Measured: Baseline and Up to 24.2 months (maximum duration of follow-up from first dose to last contact or death)

  22. Number of Participants With Change From Baseline in Hematology Data With Respect to Normal Range-Part 2 (NHL)

    Blood samples were collected for the analysis of following hematology parameters: Baso, Eosino, Hct, MCHC, MCH, MCV, Mono, Erythro and Reticu. A laboratory value that was outside the reference range was considered either high abnormal (value above the upper limit of the reference range) or low abnormal (value below the lower limit of the reference range). Baseline was defined as latest pre-dose assessment with a non-missing value, including unscheduled visits. If values were unchanged (example: High to High), or whose value became normal, were recorded in the 'To Normal or NC' category. Participants were counted twice if the participant 'Decreased to Low' and 'Increased to High' during post-Baseline. Data at worst-case post Baseline is presented.

    Measured: Baseline and Up to 7.2 months (maximum duration of follow-up from first dose to last contact or death)

  23. Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method -Part 1

    Urine samples were collected to assess urine occult blood (OB) and urine protein (Pro). The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters were recorded as no change/decreased, increase to small (indicated by trace and 1+), increase to moderate (indicated by 2+) and increase to large (indicated by 3+ and above) for urine OB and no change/decreased, increase to trace, increase to 1+, increase to 2+ and increase to 3+ for urine Pro indicating proportional concentrations in the urine sample. Baseline was the latest pre-dose assessment with a non-missing value, including unscheduled visits. Data for worst-case post Baseline is presented.

    Measured: Baseline and Up to 21.6 months (maximum duration of follow-up from first dose to last contact or death)

  24. Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method -Part 2 (MM)

    Urine samples were collected to assess urine OB and urine Pro. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters were recorded as no change/decreased, increase to small (indicated by trace and 1+), increase to moderate (indicated by 2+) and increase to large (indicated by 3+ and above) for urine OB and no change/decreased, increase to trace, increase to 1+, increase to 2+ and increase to 3+ for urine Pro indicating proportional concentrations in the urine sample. Baseline was the latest pre-dose assessment with a non-missing value, including unscheduled visits. Data for worst-case post Baseline is presented.

    Measured: Baseline and Up to 24.2 months (maximum duration of follow-up from first dose to last contact or death)

  25. Number of Participants With Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method -Part 2 (NHL)

    Urine samples were collected to assess urine OB and urine Pro. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters were recorded as no change/decreased, increase to small (indicated by trace and 1+), increase to moderate (indicated by 2+) and increase to large (indicated by 3+ and above) for urine OB. For Urine Pro., results were reported as no change/decreased, increase to trace, increase to 1+, increase to 2+ and increase to 3+ indicating proportional concentrations in the urine sample. Baseline was the latest pre-dose assessment with a non-missing value, including unscheduled visits. Data for worst-case post Baseline is presented.

    Measured: Baseline and Up to 7.2 months (maximum duration of follow-up from first dose to last contact or death)

  26. Change From Baseline in Urine Protein Excretion (24 Hour)-Part 1: GSK2857916 0.06 mg/kg

    Urine samples were collected to assess urine Pro. Baseline was the latest pre-dose assessment with a non-missing value, including unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data for change from Baseline in urine Pro. excretion (24 hour) is presented

    Measured: Baseline and Day 1 (Cycle 2 and 3)

  27. Change From Baseline in Urine Protein Excretion (24 Hour)-Part 1: GSK2857916 0.03 mg/kg and 0.12 mg/kg

    Urine samples were collected to assess urine Pro. Baseline was the latest pre-dose assessment with a non-missing value, including unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data for change from Baseline in urine Pro. excretion (24 hour) is presented

    Measured: Baseline and Day 1 (Cycle 2)

  28. Change From Baseline in Urine Protein Excretion (24 Hour)-Part 1: GSK2857916 0.24 mg/kg

    Urine samples were collected to assess urine Pro. Baseline was the latest pre-dose assessment with a non-missing value, including unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data for change from Baseline in urine Pro. excretion (24 hour) is presented

    Measured: Baseline and Day 1 (Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 13,14, 15)

  29. Change From Baseline in Urine Protein Excretion (24 Hour)-Part 1: GSK2857916 0.48 mg/kg

    Urine samples were collected to assess urine Pro. Baseline was the latest pre-dose assessment with a non-missing value, including unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data for change from Baseline in urine Pro. excretion (24 hour) is presented

    Measured: Baseline and Day 1 (Cycle 2, 3, 5, 6, 7, 8)

  30. Change From Baseline in Urine Protein Excretion (24 Hour)-Part 1: GSK2857916 0.96 mg/kg

    Urine samples were collected to assess urine Pro. Baseline was the latest pre-dose assessment with a non-missing value, including unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data for change from Baseline in urine Pro. excretion (24 hour) is presented

    Measured: Baseline and Day 1 (Cycle 2, 3, 4, 5, 6)

  31. Change From Baseline in Urine Protein Excretion (24 Hour)-Part 1: GSK2857916 1.92 mg/kg

    Urine samples were collected to assess urine Pro. Baseline was the latest pre-dose assessment with a non-missing value, including unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data for change from Baseline in urine Pro. excretion (24 hour) is presented

    Measured: Baseline and Day 1 (Cycle 2, 3, 4, 5, 6, 7, 8, 11, 12, 13, 14, 16)

  32. Change From Baseline in Urine Protein Excretion (24 Hour)-Part 1: GSK2857916 2.50 mg/kg

    Urine samples were collected to assess urine Pro. Baseline was the latest pre-dose assessment with a non-missing value, including unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data for change from Baseline in urine Pro. excretion (24 hour) is presented

    Measured: Baseline and Day 1 (Cycle 2, 3, 4, 5, 6, 7, 8, 10, 12, 13, 14, 15, 16)

  33. Change From Baseline in Urine Protein Excretion (24 Hour)-Part 1: GSK2857916 3.40 mg/kg and 4.60 mg/kg

    Urine samples were collected to assess urine Pro. Baseline was the latest pre-dose assessment with a non-missing value, including unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data for change from Baseline in urine Pro. excretion (24 hour) is presented

    Measured: Baseline and Day 1 (Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)

  34. Change From Baseline in Urine Protein Excretion (24 Hour)-Part 2 (MM)

    Urine samples were collected to assess urine Pro. Baseline was the latest pre-dose assessment with a non-missing value, including unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data for change from Baseline in urine Pro. excretion (24 hour) is presented

    Measured: Baseline and Day 1 (Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)

  35. Change From Baseline in Urine Protein Excretion (24 Hour)-Part 2 (NHL)

    Urine samples were collected to assess urine Protein. Baseline was the latest pre-dose assessment with a non-missing value, including unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data for change from Baseline in urine Protein excretion (24 hour) is presented.

    Measured: Baseline and Day 1 (Cycle 2)

Secondary outcomes (39)

  1. Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC[0-infinity]) of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM- Part 1

    Blood samples were collected at designated timepoints. Pharmacokinetic (PK) parameters of GSK2857916 were calculated using non-compartmental methods. NA indicates that geometric coefficient of variation could not be calculated for a single participant.

    Measured: Pre-dose, 30 minutes post start of infusion (SOI), at end of infusion (EOI), 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1)

  2. AUC[0-infinity] of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM- Part 1: GSK2857916 2.50 mg/kg

    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods.

    Measured: Pre-dose and EOI of Day 1 (Cycle 1)

  3. Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM- Part 1

    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods. NA indicates that geometric coefficient of variation could not be calculated for a single participant.

    Measured: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1)

  4. AUC[0-tau] of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM- Part 1: GSK2857916 2.50 mg/kg

    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods.

    Measured: Pre-dose and EOI of Day 1 (Cycle 1)

  5. Area Under the Concentration-time Curve From Zero to Time of Last Quantifiable Concentration (AUC[0-tlast]) of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM- Part 1

    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods. NA indicates that geometric coefficient of variation could not be calculated for a single participant.

    Measured: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1)

  6. AUC[0-tlast]) of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM- Part 1: GSK2857916 2.50 mg/kg

    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods.

    Measured: Pre-dose and EOI of Day 1 (Cycle 1)

  7. Clearance (CL) of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1

    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods. NA indicates that geometric coefficient of variation could not be calculated for a single participant.

    Measured: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1)

  8. CL of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1: GSK2857916 2.50 mg/kg

    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods.

    Measured: Pre-dose and EOI of Day 1 (Cycle 1)

  9. Maximum Observed Concentration (Cmax) of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1

    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods. NA indicates that geometric coefficient of variation could not be calculated for a single participant.

    Measured: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1)

  10. Cmax of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1: GSK2857916 2.50 mg/kg

    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods.

    Measured: Pre-dose and EOI of Day 1 (Cycle 1)

  11. Trough Plasma Concentration (Ctrough) of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1

    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods. NA indicates that the geometric mean and geometric coefficient of variation could not be calculated since the concentration was not quantifiable. NA indicates that geometric coefficient of variation could not be calculated for a single participant.

    Measured: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1), Pre-dose and EOI of Day 1 (Cycle 2 and Cycle 4)

  12. Ctrough of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1: GSK2857916 2.50 mg/kg

    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods.

    Measured: Pre-dose and EOI of Day 1 (Cycle 1, Cycle 2 and Cycle 4)

  13. Terminal Half-life (t1/2) of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1

    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods. NA indicates that geometric coefficient of variation could not be calculated for a single participant.

    Measured: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1)

  14. t1/2 of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1: GSK2857916 2.50 mg/kg

    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods.

    Measured: Pre-dose and EOI of Day 1 (Cycle 1)

  15. Volume of Distribution at Steady State (Vss) of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1

    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods. NA indicates that geometric coefficient of variation could not be calculated for a single participant.

    Measured: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1)

  16. Vss of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1: GSK2857916 2.50 mg/kg

    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods.

    Measured: Pre-dose and EOI of Day 1 (Cycle 1)

  17. Time to Reach Maximum Observed Concentration (Tmax) of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1

    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods. Median and full range of Tmax have been presented.

    Measured: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1)

  18. Tmax of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM - Part 1: GSK2857916 2.50 mg/kg

    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods. Median and full range of Tmax have been presented.

    Measured: Pre-dose and EOI of Day 1 (Cycle 1)

  19. Ctrough of GSK2857916 Following IV Dose in Participants With Relapsed/Refractory MM-Part 2

    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods.

    Measured: Pre-dose and EOI of Day 1 (Cycle 1, Cycle 2 and Cycle 4)

  20. Ctrough of GSK2857916 Following IV Dose in Participants With NHL-Part 2

    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods.

    Measured: Pre-dose and EOI of Day 1 (Cycle 1, Cycle 2 and Cycle 3)

  21. AUC(0-tlast) of Cys Monomethyl Auristatin F (Cys-mcMMAF) Following IV Dose of GSK2857916 in Participants With Relapsed/Refractory MM- Part 1

    Blood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods. NA indicates that geometric coefficient of variation could not be calculated for a single participant.

    Measured: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1)

  22. AUC(0-tlast) of Cys-mcMMAF Following IV Dose of GSK2857916 in Participants With Relapsed/Refractory MM- Part 1: GSK2857916 2.50 mg/kg

    Blood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods.

    Measured: Pre-dose and EOI of Day 1 (Cycle 1)

  23. Cmax of Cys-mcMMAF Following IV Dose of GSK2857916 in Participants With Relapsed/Refractory MM- Part 1

    Blood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods. NA indicates that geometric coefficient of variation could not be calculated for a single participant.

    Measured: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1)

  24. Cmax of Cys-mcMMAF Following IV Dose of GSK2857916 in Participants With Relapsed/Refractory MM- Part 1: GSK2857916 2.50 mg/kg

    Blood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods.

    Measured: Pre-dose and EOI of Day 1 (Cycle 1)

  25. Ctrough of Cys-mcMMAF Following IV Dose of GSK2857916 in Participants With Relapsed/Refractory MM- Part 1

    Blood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods. NA indicates that the geometric mean and geometric coefficient of variation could not be calculated since the concentration was not quantifiable.

    Measured: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1), Pre-dose and EOI of Day 1 (Cycle 2 and Cycle 4)

  26. Ctrough of Cys-mcMMAF Following IV Dose of GSK2857916 in Participants With Relapsed/Refractory MM- Part 1: GSK2857916 2.50 mg/kg

    Blood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods. NA indicates that the geometric mean and geometric coefficient of variation could not be calculated since the concentration was not quantifiable.

    Measured: Pre-dose and EOI of Day 1 (Cycle 1, Cycle 2 and Cycle 4)

  27. Tmax of Cys-mcMMAF Following IV Dose of GSK2857916 in Participants With Relapsed/Refractory MM- Part 1

    Blood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods. Median and full range of Tmax have been presented.

    Measured: Pre-dose, 30 minutes post-SOI, at EOI, 1, 3, 8 and 24 hours post-EOI of Day 1 (Cycle 1)

  28. Tmax of Cys-mcMMAF Following IV Dose of GSK2857916 in Participants With Relapsed/Refractory MM-Part 1: GSK2857916 2.50 mg/kg

    Blood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods. Median and full range of Tmax have been presented.

    Measured: Pre-dose and EOI of Day 1 (Cycle 1)

  29. Number of Participants With at Least One Confirmed Positive Post-Baseline Anti-drug Antibody Result- Part 1

    Serum samples were collected for the determination of anti-GSK2857916 antibodies (ADA) using a validated electrochemiluminescent (ECL) immunoassay. The assay involved screening, confirmation and titration steps. If serum samples contained ADA, they were further analyzed for the specificity of antibodies by a confirmation assay. Confirmed positive samples were titrated to obtain the titers of antibodies. The number of participants with at least one confirmed positive ADA at any time post-Baseline is presented.

    Measured: Up to 21.6 months (maximum duration of follow-up from first dose to last contact or death)

  30. Number of Participants With at Least One Confirmed Positive Post-Baseline Anti-drug Antibody Result- Part 2 (MM)

    Serum samples were collected for the determination of anti-GSK2857916 antibodies (ADA) using a validated ECL immunoassay. The assay involved screening, confirmation and titration steps. If serum samples contained ADA, they were further analyzed for the specificity of antibodies by a confirmation assay. Confirmed positive samples were titrated to obtain the titers of antibodies. The number of participants with at least one confirmed positive ADA at any time post-Baseline is presented.

    Measured: Up to 24.2 months (maximum duration of follow-up from first dose to last contact or death)

  31. Number of Participants With at Least One Confirmed Positive Post-Baseline Anti-drug Antibody Result- Part 2 (NHL)

    Serum samples were collected for the determination of anti-GSK2857916 antibodies (ADA) using a validated ECLimmunoassay. The assay involved screening, confirmation and titration steps. If serum samples contained ADA, they were further analyzed for the specificity of antibodies by a confirmation assay. Confirmed positive samples were titrated to obtain the titers of antibodies. The number of participants with at least one confirmed positive ADA at any time post-Baseline is presented.

    Measured: Up to 7.2 months (maximum duration of follow-up from first dose to last contact or death)

  32. Number of Participants With Antibodies to GSK2857916 in Serum Over Time- Part 1

    Serum samples were collected for the determination of ADA using a validated ECL immunoassay. The assay involved screening, confirmation and titration steps. If serum samples contained ADA, they were further analyzed for the specificity of antibodies by a confirmation assay. Confirmed positive (pos) samples were titrated to obtain the titers of antibodies. The number of participants with screening, confirming and negative (neg) conclusive ADA results at Baseline and different timepoints is presented.

    Measured: Baseline, Day 1 (Cycle 2, 3, 4, 6, 9, 12, 16), End of study (within 30 days [+ 7 days of last treatment or prior to the start of new anti-cancer treatment], whichever is earlier) (1 cycle=21 days)

  33. Number of Participants With Antibodies to GSK2857916 in Serum Over Time- Part 2 (MM)

    Serum samples were collected for the determination of ADA using a validated ECL immunoassay. The assay involved screening, confirmation and titration steps. If serum samples contained ADA, they were further analyzed for the specificity of antibodies by a confirmation assay. Confirmed positive samples were titrated to obtain the titers of antibodies. The number of participants with screening, confirming and negative conclusive ADA results at Baseline and different timepoints is presented.

    Measured: Baseline, Day 1 (Cycle 2, 3, 6, 7, 9, 11, 12, 16), End of study (within 30 days [+ 7 days of last treatment or prior to the start of new anti-cancer treatment], whichever is earlier) (1 cycle=21 days)

  34. Number of Participants With Antibodies to GSK2857916 in Serum Over Time - Part 2 (NHL)

    Serum samples were collected for the determination of ADA using a validated ECL immunoassay. The assay involved screening, confirmation and titration steps. If serum samples contained ADA, they were further analyzed for the specificity of antibodies by a confirmation assay. Confirmed positive samples were titrated to obtain the titers of antibodies. The number of participants with screening, confirming and negative conclusive ADA results at Baseline and different timepoints is presented.

    Measured: Baseline, Day 1 (Cycle 2, 3), End of study (within 30 days [+ 7 days of last treatment or prior to the start of new anti-cancer treatment], whichever is earlier) (1 cycle=21 days)

  35. Overall Response Rate (ORR)- Part 1

    ORR was determined by the investigator according to international myeloma working group uniform response criteria for MM (IMWG 2011). ORR was calculated as the number of participants with best overall response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) and partial response (PR).

    Measured: From the Start of Treatment (at First Dose) up to the earlier of disease progression or the start of new anti-cancer therapy (maximum duration of follow-up is 21.6 months)

  36. ORR-Part 2 (MM)

    ORR was determined by the investigator according to IMWG 2011 uniform response criteria for MM. ORR was calculated as the number of participants with best overall response of sCR, CR, VGPR and PR.

    Measured: From the Start of Treatment (at First Dose) up to the earlier of disease progression or the start of new anti-cancer therapy (maximum duration of follow-up is 24.2 months)

  37. ORR-Part 2 (NHL)

    Overall Response Rate in NHL population was determined by the investigator according to Revised Response Criteria for Malignant Lymphoma. ORR was calculated as the number of participants with confirmed complete remission (CR) or partial remission (PR). Complete remission was defined as disappearance of all evidence of disease and partial remission was defined as regression of measurable disease and no new sites.

    Measured: From the Start of Treatment (at First Dose) up to the earlier of disease progression or the start of new anti-cancer therapy (maximum duration of follow-up is 7.2 months)

  38. Clinical Benefit Rate (CBR)- Part 1

    CBR was calculated as the number of participants with best overall response of sCR, CR, VGPR, PR and minimal response (MR).

    Measured: From the Start of Treatment (at First Dose) up to the earlier of disease progression or the start of new anti-cancer therapy (maximum duration of follow-up is 21.6 months)

  39. CBR- Part 2

    CBR was calculated as the number of participants with best overall response of sCR, CR, VGPR, PR and MR.

    Measured: From the Start of Treatment (at First Dose) up to the earlier of disease progression or the start of new anti-cancer therapy (maximum duration of follow-up is 24.2 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Feb 2014 (estimated)
  2. Study start29 Jul 2014
  3. Primary completion31 Aug 2018
  4. Study completion1 Aug 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
79 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02064387
Sponsor's protocol ID
117159
Other IDs
2013-004549-18
Status last verified
Jul 2020
First submitted
13 Feb 2014
Last updated
11 Aug 2020
Data monitoring committee
No
Individual data sharing
Yes: IPD for this study will be made available via the Clinical Study Data Request site.

Publications

  • Trudel S, Lendvai N, Popat R, Voorhees PM, Reeves B, Libby EN, Richardson PG, Hoos A, Gupta I, Bragulat V, He Z, Opalinska JB, Cohen AD. Antibody-drug conjugate, GSK2857916, in relapsed/refractory multiple myeloma: an update on safety and efficacy from dose expansion phase I study. Blood Cancer J. 2019 Mar 20;9(4):37. doi: 10.1038/s41408-019-0196-6.

    PubMed 30894515

  • Collins J, van Noort M, Rathi C, Post TM, Struemper H, Jewell RC, Ferron-Brady G. Longitudinal efficacy and safety modeling and simulation framework to aid dose selection of belantamab mafodotin for patients with multiple myeloma. CPT Pharmacometrics Syst Pharmacol. 2023 Oct;12(10):1411-1424. doi: 10.1002/psp4.13016. Epub 2023 Aug 2.

    PubMed 37465991

  • Trudel S, Lendvai N, Popat R, Voorhees PM, Reeves B, Libby EN, Richardson PG, Anderson LD Jr, Sutherland HJ, Yong K, Hoos A, Gorczyca MM, Lahiri S, He Z, Austin DJ, Opalinska JB, Cohen AD. Targeting B-cell maturation antigen with GSK2857916 antibody-drug conjugate in relapsed or refractory multiple myeloma (BMA117159): a dose escalation and expansion phase 1 trial. Lancet Oncol. 2018 Dec;19(12):1641-1653. doi: 10.1016/S1470-2045(18)30576-X. Epub 2018 Nov 12.

    PubMed 30442502

  • Tai YT, Anderson KC. Targeting B-cell maturation antigen in multiple myeloma. Immunotherapy. 2015;7(11):1187-99. doi: 10.2217/imt.15.77. Epub 2015 Sep 15.

    PubMed 26370838

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GSK2857916 in people with Multiple Myeloma, run by GlaxoSmithKline at 9 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States, Canada, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Serious Adverse Events (SAEs) and Common (>=5%) Non-serious Adverse Events- Part 1 (time frame: Up to 23.5 months (maximum duration of follow-up from first dose to last contact or death)). The study lists 35 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02064387, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2020.

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