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Immutep Announces That ImmuFact(R) IMP321 Has Entered a Phase I Chemoimmunotherapy Trial in Breast Cancer
Orsay, 3rd August, 2006 -
Immutep S.A. announced today that its lead product, ImmuFact(R)
IMP321, has entered a Phase I chemoimmunotherapy clinical trial in
metastatic breast carcinoma. ImmuFact IMP321 is a potent natural
human T cell immunostimulatory factor designed to amplify the T cell immune
response.
The Company believes that this
is the first time that chemoimmunotherapy, chemotherapy followed by immune
stimulation, is being used in metastatic breast cancer.
The study is being conducted at
the René Huguenin Cancer Centre, Saint Cloud, near Paris. The design of the
study is an open-label non-randomised fixed dose-escalation trial assessing
IMP321 following paclitaxel. One of the Centre's main Principal
Investigators, Maya Gutierrez, is leading the team carrying out the trial.
Chemoimmunotherapy is a new
approach to the treatment of cancer. Chemotherapy drugs induce tumour cell
apoptosis and cause modulation of the immunological environment combined
with a burst of tumour antigen release. The resulting T cell immune response
contributes to the regression of the tumour and, importantly, may seek out
and destroy metastases. However, this initial immune response needs to be
sustained and amplified by a T-cell booster that is non-toxic and could be
given repeatedly, such as ImmuFact IMP321.
Patients will receive 6 cycles
of low-dose weekly paclitaxel at Day 1, Day 8 and Day 15 of a 4-week cycle
as first line chemotherapy with, in addition, bi-weekly IMP321 administered
the day after the paclitaxel to make a total of 12 injections of IMP321 over
24 weeks. Two dose levels of IMP321 will be studied in two cohorts of 8
patients each. The objectives of the study are i) to evaluate clinical and
laboratory safety and tolerability profiles, and ii) to determine
pharmacodynamic parameters, including CD8 T cell responses.
"We are very pleased to
start testing this innovative therapeutic approach at our Institute,"
said Dr Maya Gutierrez, Principal Investigator of this Phase I trial, "Such
sequential chemo- and then non-toxic immunotherapeutic combos may be a way
to improve the response rate and/or consolidate or stabilize the partial
tumour responses obtained with chemotherapy alone."
"We are delighted to
announce our first combination therapeutic trial with IMP321 in advanced
cancer" said Frédéric Triebel, Scientific & Medical Director of
Immutep. "Immunotherapy trials have shown their limitations in the
past in metastatic breast cancer, but this new sequential design may provide
a much greater benefit without adding toxicity to this already
well-tolerated, low-dose chemotherapy regimen."
For further information
please visit the web-site
www.immutep.com
or e-mail John Hawken, CEO, at
JBHawken@immutep.com.
Notes to Editors
Metastatic Breast Cancer
and Chemoimmunotherapy
Metastatic breast cancer remains
incurable. The failure of current approaches is generally attributed to the
outgrowth of breast tumour cells that are inherently resistant to standard
treatments. Manipulating the immune system to recognize and eradicate breast
tumour cells is a highly attractive alternative approach to disease
management. Active immunization offers multiple theoretical advantages over
all other therapies, including low toxicity and exquisite specificity. More
importantly, the potential for a sustained antitumour effect due to
immunological memory would obviate the requirement for prolonged, repetitive
cycles of therapy.
Thus the objective is to amplify natural pre-existing T cell responses specific for any known or unknown tumour antigen and to recruit and amplify new tumour-specific T cell responses occurring during a chemotherapy cycle using cytotoxic drugs known to induce tumour cell apoptosis. The direct cytolytic effect of some cytotoxic drugs, such as paclitaxel, can enhance antigen presentation by inducing tumour cell apoptosis. This mechanism of therapeutic synergy has been shown with cyclophosphamide, doxorubicin, or paclitaxel when given with dendritic cell-based vaccines. Until 5 years ago, it was thought that the T cell depletion caused by chemotherapy would make immunotherapy ineffective. However it has now been shown that, on the contrary, the vigorous T cell repopulation following depletion can be directed against the tumour, the so-called "rebound" effect. Notably, one clinical study showed that, even in the absence of concurrent vaccination, the first dose of neoadjuvant paclitaxel induced an apoptotic response within the tumour that correlated with the induction of TIL in 67% of locally advanced breast cancer patients who developed a complete clinical response (Demaria et al, 2001. Clin Cancer Res 7:3025-3030). As an example of the potential of such a chemoimmunotherapy protocol, Coley Pharmaceutical Group, Inc. obtained promising results in a randomised Phase II study of CPG 7909 (a TLR9 agonist that activates the DC network) combined with standard chemotherapy in the first-line treatment of advanced non- small cell lung cancer. The objective response rate was 37 percent among patients who received CPG 7909 plus chemotherapy against 19 percent in patients who received chemotherapy alone. These findings were further supported by a difference in reported median overall survival - 11.7 months for patients who received CPG 7909 plus chemotherapy against 6.8 months for patients who received chemotherapy alone.
Soluble LAG-3 protein is a
prognostic factor in breast cancer
ImmuFact IMP321 is
closely related to the soluble form of the LAG-3 (Lymphocyte Activation
Gene-3) protein which is a prognostic indicator for survival in breast
cancers expressing oestrogen or progesterone receptors. This was shown is a
study carried out by researchers at the René Huguenin Cancer Centre and Pr.
Frédéric Triebel when he was at the Pharmacy Faculty of University Paris 11.
These results paved the way for the current clinical trial. (Immutep Press
Release No 6, April 2006)
Centre René Huguenin de Lutte contre le Cancer
The René Huguenin Centre for the
Fight against Cancer is a comprehensive cancer centre that treats more than
3,000 new cases of cancer each year, with more than 2,000 new cases of
breast cancer. It has a medical staff of 66 practitioners. Besides
participation in therapeutic trials, the Centre has developed special
expertise in the field of tumorigenesis and pharmacogenetics of breast
cancers. Professor Jean-Nicolas Munck is the Directeur-Général of the
Centre.
Immutep S.A.
Immutep S.A. is a
biopharmaceutical company developing technologies for novel immunotherapies
for the treatment of cancer and chronic infectious diseases and new
approaches to immune response modulation. The Company's technologies are
based on the properties of LAG-3. Immutep is developing its products both
in-house and in partnership with pharmaceutical and biotech companies. The
Company was formed in 2001 by Frédéric Triebel, the scientific founder, and
John B. Hawken, a specialist in the management of biotech companies, and has
its headquarters and research facilities near Paris, France. Immutep is
backed by the Paris-based venture capital firm Innoven Partenaires and the
venture capital fund H2I, a specialist Biotech fund managed by Unicorn
Biotutors/Equitis (Paris).
The Technology
The Company's range of products
is derived from LAG-3 (CD223), an immunomodulatory protein expressed on the
surface of activated T cells. The three unique proprietary product platforms
make use of the key roles played by this natural human protein in the
regulation of the immune system.
ImmuFact(R) - T cell
Immunostimulatory Factors for amplifying the T cell response
The lead product, ImmuFact
IMP321, is a highly potent T cell immunostimulatory factor derived from the
soluble form of LAG-3 that binds, with high affinity, to MHC class II
molecules expressed by dendritic cells (DC). This binding leads to DC
maturation, migration to the lymph nodes and enhanced cross-presentation of
antigens to T cells. As a result, strong and sustained anti-tumour or
anti-viral cytotoxic T cell responses are obtained when IMP321 is injected
alone or in combination with antigens.
ImmuCcine(R) -
Immunostimulatory Vaccines
The Company is developing a
second technology that will make it possible to design novel therapeutic
vaccines with even greater potency and efficacy. Covalently linking an
antigen to IMP321 in a fusion protein results in both vectorisation of the
antigen to the DC as well as the immunostimulatory effect described above.
These "dual action" vaccines will be reserved for very difficult cases like
HIV.
ImmuTune(R) - Fine
Tuning of the Immune Response
The third technology uses
LAG-3-specific antibodies to control signalling of the membrane-bound LAG-3
molecule into activated effector T cells or regulatory T cells (Tregs) to
modulate the T cell response.
Clinical Development (ImmuFact)
Immutep has completed two
randomised single-blind escalating-dose Phase I studies in 108 healthy
individuals with IMP321 alone and combined with two well-defined standard
types of antigens to show safety of the product alone and as an adjuvant in
therapeutic vaccines. A Phase I clinical trial in metastatic renal cell
carcinoma started in September 2005 with IMP321 injected alone. The current
breast cancer study is thus the fourth clinical trial with ImmuFact
IMP321 in two years.
For more information please
contact:
Andrew Lloyd & Associates
Andrew Lloyd / Heidi Thompson
Tel: +44 1273 675100
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