This is a Phase 1/2, multi-centre, single-arm, open-label, dose-escalation study that will evaluate the safety and efficacy of IV GSK2857916 in combination with PO pomalidomide and low-dose PO dexamethasone in subjects with relapsed and/or refractory MM.
This is a Phase 1/2, multi-centre, single-arm, open-label, dose-escalation study that will evaluate the safety and efficacy of IV GSK2857916 in combination with PO pomalidomide and low-dose PO dexamethasone in subjects with relapsed and/or refractory MM. This study will consist of a Part 1 dose-finding portion and a Part 2 expansion phase. Part 1 will determine the starting dose and schedule to be used in Part 2. All subjects will receive GSK2857916 given IV either on Day 1 (Single Dose) or on Days 1 and 8 (Split Dose) in combination with pomalidomide and dexamethasone administered orally in 28-day treatment cycles. Treatment will be administered as long as there is clinical benefit. The Part 1 portion of the study will determine the MTD and/or RP2D and dose limiting toxicities (DLTs) of GSK2857916 administered in combination with pomalidomide and dexamethasone. The following dose levels of GSK2857916 in combination with 4 mg of pomalidomide and low-dose dexamethasone are to be tested in this study: 2.5 mg/kg either Single Dose (dose level 1a) or Split Dose (dose level 1b), 1.92 mg/kg Single Dose (dose level -1), and 3.4 mg/kg Split Dose (dose level 2). The Part 1 segment of the study will follow a standard 3 + 3 dose escalation design and will include assessment of the safety of treatment between each dose cohort by the Safety Review Committee (SRC) consisting of the Study Investigators and the Sponsor. When the SRC has determined the RP2D of GSK2857916, the Part 2 portion of the study will be initiated. Pomalidomide will be administered based on the current approved dose and schedule: 4 mg PO QD on Days 1 to 21 of a 28-day cycle. The starting dose of dexamethasone will be 40 mg QD on Days 1, 8, 15 and 22 of each 28-day cycle for subjects who are ≤ 75 years of age. For Subjects who are \> 75 years of age, the starting dose of dexamethasone is 20 mg QD on Days 1, 8, 15, and 22. GSK2857916 will be administered at the RP2D and treatment will continue until progressive disease (PD) or toxicity requiring discontinuation of study drug. Efficacy assessments will be conducted every cycle for the duration of the treatment period. After discontinuation from treatment, follow up will continue by phone or in person until progression from the next line of treatment or death to a maximum of 36 months after enrolment for determination of PFS2 and OS.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
120
Recommended phase 2 dose (RP2D) of GSK2857916 determined by the phase 1 portion of study will be administered in combination with pomalidomide (approved dose and schedule) and dexamethasone until progression of disease.
Cross Cancer Institute
Edmonton, Alberta, Canada
Vancouver General Hospital
Vancouver, British Columbia, Canada
CancerCare Manitoba
Winnipeg, Manitoba, Canada
QEII Health Sciences Centre
Halifax, Nova Scotia, Canada
Recommended Phase 2 Dose (RP2D)
RP2D and schedule of GSK2857916 for Part 2 will be determined by Part 1 of the study
Time frame: 9 months
Overall Response Rate (ORR)
Overall response rate will be the percentage of patients achieving partial response or better according to IMWG response criteria
Time frame: 60 months
Treatment Emergent Adverse Events
Treatment Emergent Adverse Events occurring during the study will be evaluated according to CTCAE version 5.0 to determine the safety of the study treatment
Time frame: 60 months
Progression Free Survival
Progression Free Survival according to IMWG criteria will be evaluated
Time frame: 60 months
Maximum tolerated dose (MTD)
Adverse Events occurring during the first cycle of study treatment will be evaluated against a predefined dose limiting toxicities to determine the maximally tolerated dose (MTD)
Time frame: 9 months
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Juravinski Cancer Centre
Hamilton, Ontario, Canada
London Health Sciences Centre
London, Ontario, Canada
The Ottawa Hospital
Ottawa, Ontario, Canada
Princess Margaret Cancer Centre
Toronto, Ontario, Canada
Allan Blair Cancer Centre
Regina, Saskatchewan, Canada