Analysis of the Kinetics and Effects of Vemurafenib on Intratumoral and Host Immunity in Patients With Advanced BRAFV600 Mutant Melanoma: Implications for Combination With Immunotherapy
This is a single-arm, multicenter study of vemurafenib in patients with biopsy-accessible
advanced metastatic melanoma.
The trial will consist of a screening period, a treatment phase, and one post-study
follow-up visit occurring about 30 days after the last dose of vemurafenib. Day 1 of the
study will be defined as the first day a subject receives vemurafenib. During the treatment
phase, all study assessments will be conducted on Day 1 (± 3 days) of each cycle, with the
exception of computed tomography (CT) and/or magnetic resonance imaging (MRI), which should
occur every 6 weeks (+/- 7 days).
All subjects will have biopsies performed of safely accessible tumors before starting
treatment and at 1, 2, and 4 weeks later (days 8, 15, 29). In addition, any patient with
accessible tumor at the time of progression will have a tumor biopsy performed at that time.
Mixed-effects models will be used to study the change in CD8 T cell counts per mm2 of
tissue, changes in expression of immunoinhibitory proteins (B7-H1/PD-L1, IDO, arginase), and
changes in endothelial homing receptor ligands and tumor associated chemokines at
pre-treatment at pre-treatment and at weeks 1, 2, and 4 after vemurafenib therapy. Subjects
will be treated as random effects to account for individual variability. Potential
covariates are age, gender, and ECOG performance status.
60 ml of blood for lymphocytes will be drawn on days 1, 8, 15, and 29.
Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Time course by which vemurafenib increases T cell infiltration
CD8 T cell count per mm2 of tumor
Michael B Atkins, MD
Georgetown Lombardi Comprehensive Cancer Center
United States: Food and Drug Administration
|Georgetown Lombardi Comprehsnive Cancer Center||Washington, District of Columbia 20007|