Your SlideShare is downloading. ×
0
Crizotinib
Crizotinib
Crizotinib
Crizotinib
Upcoming SlideShare
Loading in...5
×

Thanks for flagging this SlideShare!

Oops! An error has occurred.

×
Saving this for later? Get the SlideShare app to save on your phone or tablet. Read anywhere, anytime – even offline.
Text the download link to your phone
Standard text messaging rates apply

Crizotinib

1,590

Published on

Published in: Health & Medicine, Business
0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total Views
1,590
On Slideshare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
52
Comments
0
Likes
0
Embeds 0
No embeds

Report content
Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
No notes for slide
  • Wilhelm SM, Carter C, Tang L, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res . 2004;64:7099-7109. Liu L, Cao Y, Chen C, et al. Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5. Cancer Res. 2006;66:11851-11858. Avila MA, Berasain C, Sangro B, Prieto J. New therapies for hepatocellular carcinoma. Oncogene . 2006;25:3866-3884. Semela D, Dufour JF. Angiogenesis and hepatocellular carcinoma. J Hepatol . 2004;41:864-880.
  • Transcript

    • 1. Crizotinib (PF-02341066 ) c-MET inhibitor in Patient with Alk ( anaplastic lymphoma kinase ) -positive NSCLC <ul><li>MET is commonly overexpressed in lung cancer and its amplification may produce resistance to EGFR-TKI’s therapy </li></ul><ul><li>EML4 (Echinoderm Microtube associated protein Like4) Alk (Anaplastic lymphoma kinase) fusion frequency=4% adenocarcinoma (at least 7 fusion variants) </li></ul><ul><li>Crizotinib demonstrated potent growth inhibitory activity against H3122 (ALK fusion) cells </li></ul><ul><li>Patients with ALK -positive NSCLC Do not Appear to Respond to EGFR TKIs </li></ul>Inamura K et al. J Thorac Oncol 2008;3:13–17 Soda M et al. Proc Natl Acad Sci U S A 2008;105:19893–19897 Chiarle R et al. Nat Rev Cancer 2008;8(1):11–23; Mossé YP et al. Clin Cancer Res 2009;15(18):5609–5614 Shaw AT et al. J Clin Oncol 2009;27:4247–4253 ; Inversion Translocation OR Break-apart FISH assay for ALK -fusion genes Non-split signal Split signal
    • 2. Available data with crizotinib <ul><li>Objective response rate (ORR): 57% (95% CI: 46, 68%) </li></ul><ul><ul><li>57% in patients with PS 2 or 3 </li></ul></ul><ul><li>Response duration: 1 to 15 months </li></ul><ul><li>Disease Control Rate (CR/PR/SD at 8 weeks): 87% </li></ul><ul><li>(95% CI: 77, 93%) </li></ul><ul><li>No grade 3 or 4 toxicities reported. 2% of grade 3 constipation and 1% grade 2 nausea, diarrhea and vomiting, respectively. 42% grade 1 visual disturbance (changes in light/dark accommodation, no abnormalities on ophthalmologic exam) </li></ul>ORR according to previous line therapies No. prior regimens* ORR % (n/N) 0 80 (4/5) 1 52 (14/27) 2 67 (10/15) ≥ 3 56 (19/34)
    • 3. Current crizotinib clinical trials Available at: www.clinicaltrials.gov . NCT00890825 . http://www.clinicaltrials.gov/ct2/show/NCT00890825?term=NCT00890825&amp;rank=1 <ul><li>Key entry criteria (N=318) </li></ul><ul><li>Positive for ALK by central laboratory </li></ul><ul><li>1 prior chemotherapy (platinum-based) </li></ul>PHASE III PHASE II <ul><li>Key entry criteria (N=250) </li></ul><ul><li>Positive for ALK by central laboratory </li></ul><ul><li>Progressive disease in Arm B of study A8081007 </li></ul><ul><li>&gt;1 prior chemotherapy </li></ul><ul><ul><ul><li>Crizotinib 250 mg BID </li></ul></ul></ul><ul><li>Pemetrexed 500 mg/m 2 or </li></ul><ul><ul><ul><li>Docetaxel 75 mg/m 2 </li></ul></ul></ul><ul><ul><ul><li>infused on day 1 of a 21-day cycle </li></ul></ul></ul>R <ul><ul><ul><li>Crizotinib 250 mg BID </li></ul></ul></ul>PHASE III <ul><li>Key entry criteria (N=344) </li></ul><ul><li>Positive non squamous carcinoma for ALK by central laboratory </li></ul><ul><li>Chemonaive patients </li></ul><ul><ul><ul><li>Crizotinib 250 mg BID </li></ul></ul></ul><ul><li>Pemetrexed 500 mg/m 2 </li></ul><ul><ul><ul><li>Cisplatin 75 mg/m 2 or Carboplatin AUC5or6 </li></ul></ul></ul><ul><ul><ul><li>infused on day 1 of a 21-day cycle </li></ul></ul></ul>R R <ul><li>Pemetrexed 500 mg/m 2 </li></ul><ul><ul><ul><li>Cisplatin 75 mg/m 2 or Carboplatin AUC5or6 </li></ul></ul></ul><ul><ul><ul><li>infused on day 1 of a 21-day cycle </li></ul></ul></ul>Primary Endpoint: PFS Primary Endpoint: PFS Primary Endpoint: ORR
    • 4. &nbsp;

    ×