Multi-Centre Study of GSK2857916 in Combination With Pomalidomide and Dex

Titre officiel

A Phase 1/2 Multi-Centre, 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

Sommaire:

Cette étude d’augmentation de la dose de phase I/II, ouverte, multicentrique et à groupe unique évaluera l’innocuité et l’efficacité du GSK2857916 administré par voie intraveineuse (IV) toutes les 4 semaines en association avec le pomalidomide par voie orale et la dexaméthasone à faible dose par voie orale chez des sujets présentant un myélome multiple (MM) récidivant et/ou réfractaire.

Description de l'essai

Primary Outcome:

• Recommended Phase 2 Dose (RP2D)
• Overall Response Rate (ORR)

Secondary Outcome:

• Treatment Emergent Adverse Events
• Progression Free Survival
• Maximum tolerated dose (MTD)

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.

Voir cet essai sur ClinicalTrials.gov