An Open-label, Dose Escalation Study in Japanese Participants With Relapsed/Refractory Multiple Myeloma Who Have Failed Prior Anti Myeloma Treatments

A Phase I Open-Label, Dose Escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Clinical Activity of the Antibody Drug Conjugate GSK2857916 in Japanese Participants With Relapsed/Refractory Multiple Myeloma

Belantamab mafodotin (GSK2857916) is a first in class, antibody dependent cellular cytotoxicity (ADCC) enhanced, humanized immunoglobulin G1 (IgG1) antibody-drug conjugate (ADC) which binds specifically to B cell maturation antigen (BCMA) expressed on tumor cells of all participants with multiple myeloma. This is a Phase 1, open label, dose escalation study to investigate safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and clinical activity of GSK2857916 when given as monotherapy (Part 1) or given as combination therapy (Part 2). Dose escalation will follow a 3+3 design.

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Belantamab mafodotin; Drug: Bortezomib; Drug: Dexamethasone; Drug: Pomalidomide

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Aichi, Japan, 467-8602
    • GSK Investigational Site
  • Okayama, Japan, 701-1192
    • GSK Investigational Site
  • Tokyo, Japan, 135-8550
    • GSK Investigational Site
  • Tokyo, Japan, 150-8935
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• 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 studies. 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 undetected pregnancy.
• Male participants: Contraceptive use by men 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 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 females).
• 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. Exclusion Criteria
• 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 of screening.
• 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 targeted therapy.
• History of an allogeneic stem cell transplant.
• Current use of prohibited medications/device or planned use of any of these during the study period.
• 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 required criteria.
• 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 procedures.
• 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:

  1. Corrected QT interval Fridericia (QTcF) interval >=470 milliseconds (msecs) (the QT interval values must be corrected for heart rate by Fridericia's formula [QTcF])
  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 Screening.
  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 treatment. 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 study treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Belantamab mafodotin Monotherapy	Drug: Belantamab mafodotin; Belantamab mafodotin will be administered as an intravenous infusion.
Experimental: Part 2: Arm A: Belantamab mafodotin+Bortezomib/Dexamethasone	Drug: Belantamab mafodotin; Belantamab mafodotin will be administered as an intravenous infusion.; Drug: Bortezomib; Bortezomib solution for injection will be administered subcutaneously.; Drug: Dexamethasone; Dexamethasone tablets will be administered orally.
Experimental: Part 2: Arm B: Belantamab mafodotin+Pomalidomide/Dexamethasone	Drug: Belantamab mafodotin; Belantamab mafodotin will be administered as an intravenous infusion.; Drug: Dexamethasone; Dexamethasone tablets will be administered orally.; Drug: Pomalidomide; Pomalidomide capsules will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Number of participants with dose limiting toxicities (DLTs)	The number of participants with DLTs will be reported.	Day 1 to 21 of Cycle 1 (each cycle of 21 days)
Part 2: Arm A: Number of participants with DLTs	The number of participants with DLTs will be reported.	Day 1 to 21 of Cycle 1 (each cycle of 21 days)
Part 2: Arm B: Number of participants with DLTs	The number of participants with DLTs will be reported.	Day 1 to 28 of Cycle 1 (each cycle of 28 days)
Part 1 and Part 2: Number of participants with adverse events (AEs) and serious adverse events (SAEs)	AEs and SAEs will be collected.	Up to approximately 2.2 years
Part 1 and Part 2: Number of participants with abnormal hematology, clinical chemistry, urinalysis parameters	Blood and urine samples will be collected for the assessment of hematology, clinical chemistry and urinalysis parameters.	Up to approximately 2.2 years
Part 1 and Part 2: Number of participants with abnormal vital signs	Number of participants with abnormal vital signs will be assessed.	Up to approximately 2.2 years
Part 1 and Part 2: Number of participants with abnormal electrocardiogram (ECG) findings	A 12-lead ECG will be obtained using an ECG machine. Number of participants with abnormal ECG parameters will be assessed.	Up to approximately 2.2 years
Part 1 and Part 2: Number of participants with abnormal physical examination findings	Number of participants with abnormal findings in physical examination will be assessed.	Up to approximately 2.2 years
Part 1 and Part 2: Number of participants with abnormal ocular examination findings	Number of participants with abnormal ocular examination findings will be reported.	Up to approximately 2.2 years
Part 1 and Part 2: Mean Eastern Cooperative Oncology Group (ECOG) scores	The performance status of participants will be assessed using the ECOG Scale ranging from 0 (normal activity) to 5 (Dead).	Up to approximately 2.2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Area under the plasma concentration time curve from time 0 to the time of the last quantifiable concentration (AUC [0 to t]) for GSK2857916 following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.	Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15 (21-day cycle)
Part 2: Arm A: AUC (0 to t) for GSK2857916 following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.	Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (21-day cycle)
Part 2: Arm B: AUC (0 to t) for GSK2857916 following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.	Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (28-day cycle)
Part 1: Area under the plasma concentration-time curve from time 0 to the end of dosing (AUC [0 to tau]) for GSK2857916 following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.	Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15 (21-day cycle)
Part 2: Arm A: AUC (0 to tau) for GSK2857916 following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.	Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (21-day cycle)
Part 2: Arm B: AUC (0 to tau) for GSK2857916 following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.	Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (28-day cycle)
Part 1: Area under the plasma concentration-time curve from time 0 to infinite time (AUC [0 to inf]) for GSK2857916 following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.	Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15 (21-day cycle)
Part 2: Arm A: AUC (0 to inf) for GSK2857916 following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.	Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (21-day cycle)
Part 2: Arm B: AUC (0 to inf) for GSK2857916 following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.	Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (28-day cycle)
Part 1: Maximum observed plasma concentration (Cmax) for GSK2857916 following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.	Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15 (21-day cycle)
Part 2: Arm A: Cmax for GSK2857916 following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.	Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (21-day cycle)
Part 2: Arm B: Cmax for GSK2857916 following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.	Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (28-day cycle)
Part 1: Time to Cmax (Tmax) for GSK2857916 following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.	Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15 (21-day cycle)
Part 2: Arm A: Tmax for GSK2857916 following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.	Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (21-day cycle)
Part 2: Arm B: Tmax for GSK2857916 following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.	Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (28-day cycle)
Part 1: Systemic clearance (CL) for GSK2857916 following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.	Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15 (21-day cycle)
Part 2: Arm A: CL for GSK2857916 following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.	Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (21-day cycle)
Part 2: Arm B: CL for GSK2857916 following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.	Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (28-day cycle)
Part 1: Volume of distribution at steady state (Vss) for GSK2857916 following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.	Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15 (21-day cycle)
Part 2: Arm A: Vss for GSK2857916 following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.	Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (21-day cycle)
Part 2: Arm B: Vss for GSK2857916 following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.	Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (28-day cycle)
Part 1: Terminal phase half-life (T1/2) for GSK2857916 following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.	Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15 (21-day cycle)
Part 2: Arm A: T1/2 for GSK2857916 following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.	Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (21-day cycle)
Part 2: Arm B: T1/2 for GSK2857916 following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.	Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (28-day cycle)
Part 1: Concentration at the end of infusion of GSK2857916 following repeat dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.	Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15; Cycle 2 Day1, Cycle 3 Day1, Cycle 6 Day1, Cycle9 Day1, and Cycle12 Day1 (pre-dose, end of infusion); Cycle 16 Day1 (pre-dose) (21-day cycle)
Part 2: Arm A: Concentration at the end of infusion of GSK2857916 following repeat dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.	Up to approximately 2.2 years
Part 2: Arm B: Concentration at the end of infusion of GSK2857916 following repeat dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.	Up to approximately 2.2 years
Part 1: Trough plasma concentration (Ctrough) for GSK2857916 following repeat dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.	Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15; Cycle 2 Day1, Cycle 3 Day1, Cycle 6 Day1, Cycle9 Day1, and Cycle12 Day1 (pre-dose, end of infusion); Cycle 16 Day1 (pre-dose) (21-day cycle)
Part 2: Arm A: Ctrough for GSK2857916 following repeat dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.	Up to approximately 2.2 years
Part 2: Arm B: Ctrough for GSK2857916 following repeat dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.	Up to approximately 2.2 years
Part 1: Observed accumulation ratio for GSK2857916 following repeat dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.	Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15; Cycle 2 Day1, Cycle 3 Day1, Cycle 6 Day1, Cycle9 Day1, and Cycle12 Day1 (pre-dose, end of infusion); Cycle 16 Day1 (pre-dose) (21-day cycle)
Part 2: Arm A: Observed accumulation ratio for GSK2857916 following repeat dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.	Up to approximately 2.2 years
Part 2: Arm B: Observed accumulation ratio for GSK2857916 following repeat dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of GSK2857916.	Up to approximately 2.2 years
Part 1: AUC (0 to t) for Cysteine maleimidocaproyl monomethyl auristatin F (cys-mcMMAF) following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.	Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15 (21-day cycle)
Part 2: Arm A: AUC (0 to t) for cys-mcMMAF following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.	Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (21-day cycle)
Part 2: Arm B: AUC (0 to t) for cys-mcMMAF following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.	Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (28-day cycle)
Part 1: AUC (0 to tau) for cys-mcMMAF following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.	Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15 (21-day cycle)
Part 2: Arm A: AUC (0 to tau) for cys-mcMMAF following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.	Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (21-day cycle)
Part 2: Arm B: AUC (0 to tau) for cys-mcMMAF following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.	Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (28-day cycle)
Part 1: AUC (0 to inf) for cys-mcMMAF following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.	Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15 (21-day cycle)
Part 2: Arm A: AUC (0 to inf) for cys-mcMMAF following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.	Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (21-day cycle)
Part 2: Arm B: AUC (0 to inf) for cys-mcMMAF following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.	Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (28-day cycle)
Part 1: Cmax for cys-mcMMAF following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.	Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15 (21-day cycle)
Part 2: Arm A: Cmax for cys-mcMMAF following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.	Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (21-day cycle)
Part 2: Arm B: Cmax for cys-mcMMAF following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.	Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (28-day cycle)
Part 1: Tmax for cys-mcMMAF following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.	Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15 (21-day cycle)
Part 2: Arm A: Tmax for cys-mcMMAF following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.	Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (21-day cycle)
Part 2: Arm B: Tmax for cys-mcMMAF following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.	Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (28-day cycle)
Part 1: T1/2 for cys-mcMMAF following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.	Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15 (21-day cycle)
Part 2: Arm A: T1/2 for cys-mcMMAF following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.	Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (21-day cycle)
Part 2: Arm B: T1/2 for cys-mcMMAF following single dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.	Cycle1 Day1 (pre-dose, end of infusion, 2 hours after start of infusion, 24 hours after start of infusion); Cycle1 Day4; one sample between Cycle1 Day8 to Day15 (28-day cycle)
Part 1: Concentration at end of infusion for cys-mcMMAF following repeat dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.	Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15; Cycle 2 Day1, Cycle 3 Day1, Cycle 6 Day1, Cycle9 Day1, and Cycle12 Day1 (pre-dose, end of infusion); Cycle 16 Day1 (pre-dose) (21-day cycle)
Part 2: Arm A: Concentration at end of infusion for cys-mcMMAF following repeat dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.	Up to approximately 2.2 years
Part 2: Arm B: Concentration at end of infusion for cys-mcMMAF following repeat dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.	Up to approximately 2.2 years
Part 1: Ctrough for cys-mcMMAF following repeat dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.	Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15; Cycle 2 Day1, Cycle 3 Day1, Cycle 6 Day1, Cycle9 Day1, and Cycle12 Day1 (pre-dose, end of infusion); Cycle 16 Day1 (pre-dose) (21-day cycle)
Part 2: Arm A: Ctrough for cys-mcMMAF following repeat dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.	Up to approximately 2.2 years
Part 2: Arm B: Ctrough for cys-mcMMAF following repeat dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.	Up to approximately 2.2 years
Part 1: Observed accumulation ratio for cys-mcMMAF following repeat dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.	Cycle1 Day1 (pre-dose, end of infusion, 1, 3, 8, 24 hours post-infusion), Day8, Day15; Cycle 2 Day1, Cycle 3 Day1, Cycle 6 Day1, Cycle9 Day1, and Cycle12 Day1 (pre-dose, end of infusion); Cycle 16 Day1 (pre-dose) (21-day cycle)
Part 2: Arm A: Observed accumulation ratio for cys-mcMMAF following repeat dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.	Up to approximately 2.2 years
Part 2: Arm B: Observed accumulation ratio for cys-mcMMAF following repeat dose administration	Blood samples will be collected at indicated time points for pharmacokinetic analysis of cys-mcMMAF.	Up to approximately 2.2 years
Part 1 and Part 2: Number of participants who develop anti-drug antibodies (ADAs) against GSK2857916	Serum samples will be collected for analysis of presence of anti-GSK2857916 antibodies by a validated electrochemiluminescent immunoassay.	Up to approximately 2.2 years
Part 1 and Part 2: Titers of anti-GSK2857916 antibodies	Serum samples will be collected for analysis of presence of anti-GSK2857916 antibodies by a validated electrochemiluminescent immunoassay.	Up to approximately 2.2 years
Part 1 and Part 2: Overall response rate	Overall response rate is defined as the percentage of participants with a confirmed partial response or better, according to the International Myeloma Working Group (IMWG) response criteria, as assessed by the investigator.	Up to approximately 2.2 years
Part 1 and Part 2: Clinical benefit rate	Clinical benefit rate is defined as the percentage of participants with a confirmed minimal response (MR) or better, according to the IMWG response criteria, as assessed by the investigator.	Up to approximately 2.2 years

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2019
• Primary Completion (Actual): April 6, 2023
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: January 31, 2019
• First Submitted That Met QC Criteria: January 31, 2019
• First Posted (Actual): February 4, 2019

Study Record Updates

• Last Update Posted (Actual): November 14, 2023
• Last Update Submitted That Met QC Criteria: November 10, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Japanese; Dose-escalation; Relapsed/Refractory Multiple Myeloma; Antibody drug conjugate; GSK2857916
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dexamethasone; Pomalidomide; Bortezomib
• Other Study ID Numbers: 207504

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No