Loading...
Loading...
OncoMed Pharmaceuticals, Inc.
, a clinical-stage company
developing novel therapeutics that target cancer stem cells (CSCs), or
tumor-initiating cells, presented data in two posters highlighting the
company's translational research and biomarker efforts for its tarextumab
(anti-Notch2/3, OMP-59R5) and demcizumab (anti-DLL4, OMP-21M18) clinical
programs. These data were presented at the 26^th EORTC-NCI-AACR Symposium on
Molecular Targets and Cancer Therapeutics.
"The data from the Phase 1b clinical trials of tarextumab and demcizumab
demonstrate that our preclinical understanding of on-target drug activity and
predictive biomarkers is being validated in the clinic as we study actual
patient tumor samples," said Jakob Dupont, M.D., OncoMed's Chief Medical
Officer. "In the ALPINE Phase 1b study in advanced pancreatic cancer, we see
clear evidence that tarextumab modulates the Notch cancer stem cell pathway in
patient samples and that there is a potential association between tumors that
show higher levels of Notch3 gene expression and best responses to tarextumab
treatment. In the demcizumab poster presentation, a case study is described
from our Phase 1b trial in pancreatic cancer in which the tumor response to
treatment that occurred in the clinic correlates with what we observe using
patient-derived xenograft models. This may provide insights into the
development of potential biomarkers of response to demcizumab treatment in
that program."
Tarextumab
OncoMed researchers analyzed tissue samples including serial tumor biopsies
from patients with metastatic pancreatic cancer in the Phase 1b ALPINE
clinical trial of tarextumab in combination with gemcitabine plus Abraxane^®
(paclitaxel protein-bound particles for injectable suspension) (albumin
bound). Pharmacodynamic biomarkers showed that tarextumab at doses of 7.5mg/kg
and above had marked inhibitory effects on genes associated with Notch
signaling and stem cell cells in hair follicles and blood cells. Genes
indicating stem cell differentiation were up-regulated at the same doses in
these samples. In four paired serial tumor biopsies, Notch3 protein levels
were significantly reduced by the combination of
tarextumab-gemcitabine-Abraxane. Importantly, gene signatures reflective of
Notch signaling, tumor metastasis, and cancer stem cells were all markedly
down-regulated following treatment with tarextumab-gemcitabine-Abraxane
relative to baseline tumors. These data are consistent with the proposed
mechanism of action of tarextumab to inhibit Notch signaling and to reduce
cancer stem cells in tumors. The dose of tarextumab in the ongoing Phase 2
portion of the ALPINE study is 15mg/kg every 2 weeks.
Using OncoMed's proprietary Notch3 gene expression assay for predictive
biomarkers, OncoMed researchers observed an emerging trend suggesting that
patients with higher levels of tumor-derived Notch3 gene expression at
baseline exhibit improved response to tarextumab treatment. Notch3 gene
expression was evaluable in pancreatic tumor samples from 80 percent of the
patients enrolled in the Phase 1b trial. Notch3 gene expression is now being
evaluated as a predictive biomarker for tarextumab in the Phase 2 portion of
the ALPINE clinical trial.
These data were presented today by lead author Ann M. Kapoun, Ph.D., OncoMed's
Vice President, Translational Medicine, in a poster titled: Biomarker analysis
in Phase 1b study of anti-cancer stem cell antibody Tarextumab (TRXT) in
combination with nab-paclitaxel and gemcitabine (Nab-P+Gem) demonstrates
pharmacodynamic (PD) modulation of the Notch pathway in patients (pts) with
untreated metastatic pancreatic cancer (mPC) (abstract# 465).
Demcizumab
In the demcizumab presentation, a patient tumor sample from the Phase 1b
clinical trial of demcizumab combined with standard of care was evaluated
using OncoMed's proprietary patient-derived xenograft models and the
anti-tumor response was compared between the clinical and preclinical
studies. The Phase 1b patient progressed rapidly on treatment with a
combination of demcizumab and gemcitabine. When a tumor derived from the Phase
1b patient was grown in a xenograft model, the new tumor was also insensitive
to gemcitabine and the combination of demcizumab plus gemcitabine. This tumor
was significantly more sensitive to the triple combination using
demcizumab-gemcitabine-Abraxane. These data suggest that OncoMed's
patient-derived xenograft models can mirror activity in the clinic. Analysis
of key characteristics of responsive tumors relative to non-responsive tumors
may provide insights into potential biomarkers of sensitivity to demcizumab
treatment.
Data from this study were presented during the Preclinical Models poster
session on Wednesday, November 19, 2014 by Manuel Hidalgo, M.D., Ph.D.,
CNIO-CIOCC-START, a lead clinical investigator for the demcizumab Phase 1b
study, in a poster titled: Preclinical and Clinical Activity of Anti-DLL4
(Demcizumab) in Combination with Gemcitabine Plus nab-Paclitaxel in Pancreatic
Cancer (abstract #166).
"The biomarker programs associated with each of our clinical candidates
directly informs and guides predictive biomarker efforts in randomized Phase 2
clinical trials and beyond," said Paul J. Hastings, OncoMed's Chairman and
Chief Executive Officer. "This approach makes for smarter, more strategic drug
development that we believe will translate into improved patient care and
outcomes."
Loading...
Loading...
© 2024 Benzinga.com. Benzinga does not provide investment advice. All rights reserved.
Benzinga simplifies the market for smarter investing
Trade confidently with insights and alerts from analyst ratings, free reports and breaking news that affects the stocks you care about.
Join Now: Free!
Already a member?Sign in