ibrutinib first in class inhibitor of btk n.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
Ibrutinib : First-in Class Inhibitor of BTK PowerPoint Presentation
Download Presentation
Ibrutinib : First-in Class Inhibitor of BTK

Loading in 2 Seconds...

play fullscreen
1 / 6

Ibrutinib : First-in Class Inhibitor of BTK - PowerPoint PPT Presentation


  • 558 Views
  • Uploaded on

O. N. H. 2. N. N. N. N. N. O. Ibrutinib : First-in Class Inhibitor of BTK. Forms a specific and irreversible bond with cysteine-481 in BTK Highly potent BTK inhibition at IC 50 = 0.5 nM Orally administered with once daily dosing resulting in 24-hr target inhibition

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Ibrutinib : First-in Class Inhibitor of BTK' - kamala


Download Now An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
ibrutinib first in class inhibitor of btk

O

N

H

2

N

N

N

N

N

O

Ibrutinib: First-in Class Inhibitor of BTK
  • Forms a specific and irreversible bond with cysteine-481 in BTK
  • Highly potent BTK inhibition at IC50 = 0.5 nM
  • Orally administered with once daily dosing resulting in 24-hr target inhibition
  • In CLL cells promotes apoptosis, inhibits ERK1/AKT phosphorylation, NF-κB DNA binding, CpG mediated proliferation
  • Inhibits CLL cell migration and adhesion
  • No cytotoxic effect on T-cells or NK-cells

Honigberg LA et al: Proc Natl Acad Sci U S A.107:13075, 2010

Herman SEM et al: Blood 117: 6287-6296, 2011

Ponader, et al., ASH Meeting Abstracts 116:45, 2010

Ibrutinib

PCI-32765

slide3

Potential Role for BCR Signalling in HCL

Sivina M et al. ASH Annual Meeting 2012 Abstract #1802

nci 9268 ibrutinib for relapsed hcl objectives
NCI 9268Ibrutinibfor Relapsed HCL: Objectives

Primary Objective

To determine the overall response rate after 32 wks of ibrutinib therapy

Secondary Objectives

  • To characterize the toxicity and tolerability of single-agent ibrutinib
  • To characterize the progression-free (PFS) and overall survival (OS)
  • To determine the rate of MRD-negative CR at 32 weeks
  • To characterize immunologic outcomes during ibrutinib treatment
  • To explore the effect of ibrutinib on traditional and new biomarkers in HCL including: 
    • BRAFV600E in expression
    • pERK regulation, as well as other potential protein kinase targets
    • Serum soluble IL-2 receptor levels
    • MRD
slide5

NCI 9268Ibrutinib for Relapsed HCL: Eligibility

  • Histologically confirmed hairy cell leukemia (HCL) or variant hairy cell leukemia (vHCL)
  • For HCL:
    • ≥1 prior purine nucleoside analog-containing regimen, or
    • Relapsed or de novo disease if medically unfit for purine nucleoside analog treatment
  • For vHCL:
    • Both previously untreated and relapsed patients are eligible
  • Preserved end-organ function, ECOG ≤ 2
  • Requires therapy
    • Hgb <11g/dL, plts <100K/mL, ANC <1,000/mL, enlarging nodes ≥2cm
    • Progressive organomegaly
    • Progressive disease-related constitutional symptoms
slide6

NCI 9268Ibrutinib for Relapsed HCL: Schema

N = 44 patients

6 participating centers