Transcript Document

Commercial Benchmark: Herceptin
• Antibody targeting HER2 cell surface receptor
• Over expressed on certain breast cancers
– Patients selected based on degree of over
expression
• 2nd antibody approved by FDA
• $5.5 billion annualized worldwide sales in
2010, virtually all of which is in breast cancer
• Each 1% royalty (UCLA) is worth $55M/year!
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FDA Workshop on Criteria for use of Omnics-based Predictors in Clinical Trials
Rockville, MD, June 23, 2011
Donna Roscoe, Ph.D. FDA- Criteria for Disease Biomarkers
1. The tissue sample or biomarker must be representative of the disease in the patient.
2. FDA requires a detailed biomarker assay protocol which shows that the assay is robust.
The SOP should include quantitative information regarding the precision, sensitivity,
specificity, linear range, and reproducibility of the biomarker assay.
3. The biomarker assay should yield similar results when the assay is done in several
independent labs.
4. The applicant organization should provide an explanation for any differences observed in
the results obtained with formalin-fixed tissues versus frozen tissues.
5. The FDA is usually not too concerned whether the biomarker analysis was done on the
primary or the metastatic tumor.
6. Invasive biomarker assays will require IND approval from the FDA
Biomarker Studies Conducted in the HCC Translational
Research Lab
CTO#101376 Phase 2 Trial of Ofatumumab and Lenalidomide in
CLL. L. Costa, R. Stuart, D. Fernandes. HCC initiated study funded
by GSK. Measure population of biomarker CD16+/CD56+ NK
cells to see if Lenalidomide ↑ ADCC by Ofatumumab.
Prevalence of Mast Cell Disease in Gulf War Illness Patients. L.
Afrin and D. Fernandes. VA Merit Award submitted. Examine
KitD816V and other kit mutations that may cause constitutive
activation of kit and mast cell activation disease.
Phase II trial of AS1411 →AraC in refractory AML. R. Stuart, D.
Fernandes. Funded by Antisoma. Determine whether AS1411 is
targeting nucleolin by measuring nucleolin and BCL-2 mRNA .
Effect of AS1411 on the Levels of Nucleolin and
Bcl-2 mRNAs
% of Control
Normalized to b-action
100
Nucleolin
Bcl-2
80
60
40
20
0
0
24
48
Hours
72
96
Nucleolin overexpression in spleen sections from mice
injected with human AML. Cells.
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Cellular localization of nucleolin in malignant and normal
breast cancer cells
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Large Market Opportunity
Cancer Cell Lines That Over-express Nucleolin and/or are Killed Subsequent to Nucleolin Inhibition
Breast cancer
MCF7, T-47D, BT-549, MDA-N, MDA-MB-231, ZR7S-1
Lung cancer
A549, NCI-H322M, NCI-H460, EKVX, HOP-92, NCI-H299, CaLu1, NCI-H1385, NCI-H82, CaLu6
Prostate cancer
DU145, PC-3, CA-HPV-10
Colon cancer
HCC 2998, HT-29, KM12, HCT-116, SW620, HCT-15, LS174T
Pancreatic cancer
PANC-1, MIA-PaCa-2, PANC-1
Renal cell carcinoma
786-0, CAKI-1, RXF393, TK10, A498, ACHN, SN12C
Ovarian cancer
IGROV, OVCAR-3, OVCAR-4, OVCAR-5
Cervical cancer
HeLa
Leukemia & lymphoma
CCRF-CEM, SR, HL60, K-562, RPMI-6226, U937, Meg0, MV4-11
Melanoma
LOX-IMVI, SK-MEL-2, A375, SK-MEL-28, MDA-MB-435
Glioblastoma
SF-268, U87-MG
Neuroblastoma
IMR 32, Lan 5
Sarcoma
HT-1080
Gastric cancer
KATOIII, HGC27
Data from NCI Tumor Cell Line Screen of AS1411;
Bates et al, Exp Mol Path 86:151, 2009; Hoel et al., J. Immunol. 182:65.10, 2011