Multi-Center Study of GSK2857916 in Combination With Pomalidomide and Dex
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|ClinicalTrials.gov Identifier: NCT03715478|
Recruitment Status : Not yet recruiting
First Posted : October 23, 2018
Last Update Posted : October 23, 2018
|Condition or disease||Intervention/treatment||Phase|
|Relapsed and/or Refractory Multiple Myeloma||Drug: GSK2857916 in combination with Pomalidomide and Dex||Phase 1 Phase 2|
This is a Phase 1/2, multi-centre, single-arm, open-label, dose-escalation study that will evaluate the safety and efficacy of GSK2857916 given IV q 4 weeks 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 GSK2857916, pomalidomide and low dose dexamethasone dose-finding portiont and a Part 2 expansion phase. The Part 1 part will determine the starting dose and schedule to be used in the Part 2 segment of the study. All subjects will receive GSK2857916 given IV q 4 weeks 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 I portion of the study will determine the MTD and/or RP2D and dose limiting toxicities (DLTs) of GSK2857916 administered IV q 4 weeks 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 (dose level 1) and 3.4 mg/kg (dose level 2). An additional lower dose level of 1.92 mg/kg (dose level -1) maybe tested if 2 or more DLTs are observed in dose level 1. 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 of each 28-day cycle. 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 (Clinical Trial)|
|Estimated Enrollment :||52 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1/2 Multi-Center, Open Label, Dose Escalation Study to Determine the RP2D, Safety and Efficacy of GSK2857916 in Combination With Pomalidomide and Low-Dose Dexamethasone in Subjects With Relapsed and/or Refractory Multiple Myeloma|
|Estimated Study Start Date :||December 1, 2018|
|Estimated Primary Completion Date :||June 1, 2023|
|Estimated Study Completion Date :||December 31, 2024|
Experimental: GSK2857916 with POM and Dex
This will be a single arm study of GSK2857916 administered with POM and Dex. GSK2857916 will be administered IV q 4 weeks for each 28 day cycle while pomalidomide will be administered orally on days 1-21 at 4 mg. Dexamethasone will be administered at 40 for patients 75 years old or younger or 20 mg for patients older than 75 on days 1, 8, 15, 22
Drug: GSK2857916 in combination with Pomalidomide and Dex
Recommended phase 2 dose 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 dosease
- Maximum tolerated dose (MTD) [ Time Frame: 9 months ]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)
- Overall Response Rate (ORR) [ Time Frame: 60 months ]Overall response rate will be the percentage of patients achieving partial response or better according to IMWG response criteria
- Treatment Emergent Adverse Events [ Time Frame: 60 months ]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
- Progression Free Survival [ Time Frame: 60 months ]Progression Free Survival according to IMWG criteria will be evaluated