ABSCIENCES (EPA:AB) AB Science: authorization to initiate phase 2 in stomach cancer with masitinib - Masitinib clinical development program in solid tumors now accounts for 11 indications
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17/01/2011 08:45
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Paris, January 17th, 2011 - 8:45 am
AB Science announces authorization to initiate phase 2 in stomach cancer with
masitinib
Masitinib clinical development program in solid tumors now accounts for
11 indications
AB Science SA (NYSE Euronext - FR0010557264 - AB), a pharmaceutical company
specialising in the research, development and commercialisation of protein
kinase inhibitors (PKIs), announced today the authorisation granted by Afssaps
to start a phase 2 clinical study in stomach cancer.
AB Science is now evaluating masitinib in eleven indications in solid tumors,
eight in phases 2, in second line treatment of gastro-intestinal stromal tumor
(GIST), lung cancer, prostate cancer, colorectal cancer, triple negative breast
cancer, metastatic breast cancer, metastatic melanoma, and stomach cancer, and
three in phase 3 in pancreatic cancer, first line treatment of GIST and in
metastatic melanoma expressing JM mutation of c-Kit.
Except for GIST and melanoma bearing the JM mutation of c-kit, where masitinib
is tested in monotherapy because the main target is the JM mutation of c-kit, in
the remaining 9 indications masitinib is tested in combination with standard of
care chemotherapy. Indeed, masitinib has proved to sensitize in vitro and in
grafted mice models several standard of care chemotherapies in various solid
tumors cell lines.
Alain Moussy, Chairman and CEO of AB Science declared " Besides the three phase
3 studies already launched in pancreatic cancer, GIST first line and melanoma
bearing the JM mutation of c-kit, the objective of these proof of concept phases
2 studies in solid tumors is to define in which cancers masitinib can improve
progression free survival and survival. The position of masitinib is mainly in
resistance to first line treatment and in metastatic tumors, where the medical
need is the maximum. In case of success, this set of indications represents a
huge potential, as overcoming resistance to chemotherapy remains a daunting
problem. These eight phase 2 studies and three phase 3 studies in oncology are
fully financed ".
Details of the clinical development program (on next page).
About masitinib
Masitinib is a new orally administered tyrosine kinase inhibitor that targets
mast cells, important cells for immunity, as well as a limited number of kinases
that play key roles in various cancers. Owing to its novel mechanism of action,
masitinib can be developed in a large number of conditions in oncology, in
inflammatory diseases and in certain diseases of the central nervous system.
Through its activity of inhibiting certain kinases that are essential in some
oncogenic processes, masitinib may have an effect on tumour regression, alone or
in combination with chemotherapy. Through its activity on the mast cell and
certain kinases essential to the activation of the inflammatory cells and
fibrosing tissue remodelling, masitinib can have an effect on the symptoms
associated with some inflammatory and central nervous system diseases.
About AB Science
Founded in 2001, AB Science is a pharmaceutical company specialising in the
research, development and commercialisation of protein kinase inhibitors (PKIs),
a new class of targeted molecules whose action is to modify signalling pathways
within cells. Through these PKIs, the Company targets diseases with high unmet
medical needs (cancer, inflammatory diseases and central nervous system
diseases), in both human and veterinary medicines. Thanks to its extensive
research and development capabilities, AB Science has its own portfolio of
molecules. Masitinib, a lead compound, has already been registered in veterinary
medicine in Europe and is pursuing nine phase 3 studies in human medicine,
including four studies on-going in pancreatic cancer, GIST, in metastatic
melanoma expressing JM mutation of c-Kit, and mastocytosis.
Further information is available on AB Science's website: www.ab-science.com
This document contains prospective information. No guarantee can be given as
for the realisation of these forecasts, which are subject to those risks
described in documents deposited by the Company to the Authority of the
financial markets, including trends of the economic conjuncture, the financial
markets and the markets on which AB Science is present.
* * *
AB Science - Financial Communication & Press Relations
Citigate Contacts Citigate Dewe Rogerson :
Dewe Rogerson Agnès Villeret - Tel: +33 1 53 32 78 95 -
agnes.villeret@citigate.fr
* * *
DETAILS OF THE CLINICAL DEVELOPMENT PROGRAM IN SOLID TUMORS
Status of program of clinical studies of masitinib in solid tumors
Clinical Studies Status at IPO Current status
Masitinib in monotherapy (JM mutation of c-Kit)
1 - Gist first line (phase 3) Recruitment on-going Recruitment on-going
2 - Metastatic melanoma bearing
JM mutation of c-Kit (phase 3) Not initiated Recruitment on-going
3 - GIST second line (phase 2) Recruitment on-going Recruitment on-going
Masitinib in combination with chemotherapy
4- Pancreatic cancer (phase 3) Recruitment on-going Recruitment completed
5- Lung cancer (phase 2) Authorised (Afssaps) Recruitment on-going
6- Prostate cancer (phase 2) Authorised (Afssaps) Recruitment on-going
7- Colorectal cancer (phase 2) Authorised (Afssaps) Recruitment on-going
8- Breast cancer triple negative
(phase 2) Authorised (Afssaps) Recruitment on-going
9- Metastatic breast cancer
(phase 2) Authorised (Afssaps) Recruitment on-going
10- Metastatic melanoma (phase 2) Not initiated First patient enrolled
11- Stomach cancer (phase 2) Not initiated Authorised (Afssaps)
Scientific rationale for developing masitinib in solid tumors in combination
with chemotherapies
Masitinib is a novel inhibitor targeting specifically c-kit, FAK, PDGFR, and
FGFR3, thus it could limit cell proliferation, cell migration and/or tumour
vascularisation. It has also been shown that it can potentiate chemotherapeutic
agents or sensitize resistant cells to chemotherapeutic agents.
Masitinib is an effective antimastocyte, exerting a direct anti-proliferative
and pro-apoptotic action on mast cells and reducing secretion of mast cell
mediators through its inhibition of KIT signalling. Evidence indicates that
recruitment of inflammatory cells, especially infiltration by mast cells,
facilitates the growth and spread of some cancers by producing molecules that
enhance tumour invasiveness. Therefore, inhibition of mast cell function may
prove to be therapeutically beneficial in restraining the growth of numerous
cancers, even those without a direct association with mast cell proliferation.
In addition to its antiproliferative properties, masitinib can also regulate the
activation of mast cells through its targeting of Lyn and Fyn, key components of
the transduction pathway leading to IgE induced degranulation. This can be
observed in the inhibition of FceRI-mediated degranulation of human cord blood
mast cells. It is thought that inhibition of Lyn kinase activity may also
inhibit IgE independent degranulation and as such has potential benefits in
defence against metastasis and drug-resistance.
Masitinib may reduce angiogenesis and enhance the chemotherapy sensitivity and
availability at the tumour site via inhibition of PDGFR. Recent studies have
suggested that PDGFR-beta inhibition reduces tumour interstitial pressure and
thus, increases the uptake of concomitantly administered drugs. Inhibition of
PDGFR kinase activity may also result in direct tumour cell growth arrest and
apoptosis if PDGFR is constitutively activated.
FAK influences cell proliferation, survival, and migration, and has been
associated with tumour progression, metastasis and chemoresistance. Masitinib
can block the FAK pathway in cells through the inhibition of FAK phosphorylation
activity, without blocking its enzymatic activity.
Altogether, this could provide a mechanism of action for masitinib's
chemosensitisation properties, i.e. through the reduction of tumour progression
and/or improved drug delivery and/or the inhibition of mast cell migration and
activation; thereby explaining the observed therapeutic benefits of masitinib.
Characteristics of the phase 3 GIST first line
A prospective, multicenter, randomized, open-label, active-controlled,
2-parallel group, phase 3 study to compare efficacy and safety of masitinib at
7.5 mg/kg/day to imatinib at 400 or 600 mg in treatment of patients with
gastro-intestinal stromal tumour in first line medical treatment
Patients will be randomized in two groups:
Group 1: Patients will receive masitinib at 7,5 mg/kg/day
Group 2: Patients will receive imatinib at 400 or 600 mg per day
The primary criterion will be the Overall Progression Free Survival (PFS),
defined as the delay between the date of randomisation to the date of documented
progression or any cause of death during the study. Overall Survival will be the
main secondary criterion.
Characteristics of the phase 3 study in metastatic melanoma bearing JM mutation
of c-kit
A prospective, multicenter, randomized, open-label, active-controlled,
two-parallel groups, phase 3 study to compare the efficacy and safety of
masitinib at 7.5 mg/kg/day to dacarbazine in the treatment of patients with
non-resectable or metastatic stage 3 or stage 4 melanoma carrying a
mutation in the juxta membrane domain of c-kit.
Patients will be randomized in two groups:
Group 1: Patients will receive masitinib
Group 2: Patients will receive dacarbazine
The primary criterion will be the Overall Progression Free Survival (PFS),
defined as the delay between the date of randomisation to the date of documented
progression or any cause of death during the study. Overall Survival will be the
main secondary criterion.
Characteristics of the phase 2 GIST second line
A prospective, multicenter, randomized, open-label, 2-parallel group, Phase 2
study to compare efficacy and safety of masitinib at 12 mg/kg/day to sunitinib
at 50 mg/day in treatment of patients with gastro-intestinal stromal tumor
resistant to imatinib
Patients will be randomized in two groups:
Group 1: Patients will receive masitinib at 12 mg/kg/day
Group 2: Patients will receive sunitinib at 50 mg/day
The primary criterion will be the Overall Progression Free Survival (PFS),
defined as the delay between the date of randomisation to the date of documented
progression or any cause of death during the study. Overall Survival will be the
main secondary criterion.
Characteristics of the phase3 in pancreatic cancer
A prospective, multicenter, randomized, double-blind, placebo-controlled,
2-parallel group, Phase 3 study to compare efficacy and safety of masitinib at
9 mg/kg/day in combination with gemcitabine, to placebo in combination with
gemcitabine, in treatment of patients with advanced/metastatic pancreatic
cancer.
Patients will be randomized in two groups:
Group 1: Patients will receive masitinib at 9 mg/kg/day plus gemcitabine
Group 2: Patients will receive matching placebo plus gemcitabine
The primary criterion will be the Overall Survival. Progression Free Survival
(PFS) will be the second criterion.
Characteristics of the phase 2 study in lung cancer
A prospective, multicentre, randomised, open-label, 2-parallel groups, phase 2
study to evaluate efficacy and safety of masitinib at 9 mg/kg/day in combination
with docetaxel or in combination with gemcitabine in the treatment of patients
with metastatic non-small cell lung cancer in progression after first line
treatment.
Patients will be randomized in two groups:
Group 1: Patients will receive masitinib at 9 mg/kg/day in combination with
docetaxel
Group 2: Patients will receive masitinib at 9 mg/kg/day in combination with
gemcitabin
The primary criterion will be the Overall Progression Free Survival (PFS),
defined as the delay between the date of randomisation to the date of documented
progression or any cause of death during the study. Overall Survival will be the
main secondary criterion.
Characteristics of the phase 2 study in prostate cancer
This is a prospective, multicenter, randomized, open-label, 2-parallel group,
Phase 2 study to evaluate the efficacy and the safety of masitinib at
9 mg/kg/day in combination with docetaxel or with gemcitabine in metastatic
Hormone Refractory Prostate Cancer (HRPC) in progression after first line of
treatment.
Patients will be randomized in two groups:
Group 1: Patients will receive masitinib at 9 mg/kg/day in combination with
docetaxel and prednisone
Group 2: Patients will receive masitinib at 9 mg/kg/day in combination with
gemcitabine
The primary criterion will be the Overall Progression Free Survival (PFS),
defined as the delay between the date of randomisation to the date of documented
progression or any cause of death during the study. Overall Survival will be the
main secondary criterion.
Characteristics of the phase 2 study in colorectal cancer
This is a prospective, multicentre, randomized, open-label, 3-parallel groups,
phase 2 study to evaluate efficacy and safety of masitinib at 9 mg/kg/day in
combination with oxaliplatin, 5-fluorouracil (5-FU) and folinic acid (FOLFOX) or
in combination with irinotecan, 5-fluorouracil (5-FU) and folinic acid (FOLFIRI)
or in combination with gemcitabine (GEM) in the treatment of patients with
metastatic colorectal cancer in progression after a first line treatment.
Patients will be randomised in three groups:
Group 1: Patients will receive masitinib in combination with oxaliplatin
5-fluorouracil (5-FU) and folinic acid (modified FOLFOX protocol);
Group 2: Patients will receive masitinib in combination with irinotecan,
5-fluorouracil (5-FU) and folinic acid (FOLFIRI protocol);
Group 3: Patients will receive masitinib in combination with gemcitabine.
The primary criterion will be the Overall Progression Free Survival (PFS),
defined as the delay between the date of randomisation to the date of documented
progression or any cause of death during the study. Overall Survival will be the
main secondary criterion.
Characteristics of the phase 2 study in breast triple negative cancer
This is a prospective, multicentre, open-label, randomised, phase 2 study to
evaluate efficacy and safety of masitinib at 9 mg/kg/day in association with
gemcitabine or carboplatin or gemcitabine plus carboplatin in patients with a
triple negative metastatic or locally advanced breast cancer.
Patients will be randomised in three groups:
Group 1: Patients will receive masitinib at 9 mg/kg/d in association with
gemcitabine;
Group 2: Patients will receive masitinib at 9 mg/kg/d in association with
carboplatin;
Group 3: Patients will receive masitinib at 9 mg/kg/d in association with
gemcitabine plus carboplatin.
The primary criterion will be the Overall Progression Free Survival (PFS),
defined as the delay between the date of randomisation to the date of documented
progression or any cause of death during the study. Overall Survival will be the
main secondary criterion.
Characteristics of the phase 2 study in metastatic cancer
This is a prospective, multicentre, open-label, randomised, phase 2 study to
evaluate efficacy and safety of masitinib in combination with gemcitabine or
carboplatin or capecitabine in patients with a metastatic or locally advanced
breast cancer (all hormonal status tumour except triple negative tumour) and who
relapsed after a first line chemotherapy.
Patients will be randomised in three groups:
Group 1: Patients will receive masitinib at 9 mg/kg/d or 6 mg/kg/day in
association with gemcitabine
Group 2: Patients will receive masitinib at 9 mg/kg/d or 6 mg/kg/day in
association with carboplatin
Group 3: Patients will receive masitinib at 9 mg/kg/d or 6 mg/kg/day in
association with capecitabine
The primary criterion will be the Overall Progression Free Survival (PFS),
defined as the delay between the date of randomisation to the date of documented
progression or any cause of death during the study. Overall Survival will be the
main secondary criterion.
Characteristics of the phase 2 study in metastatic melanoma
This is a prospective, multicentre, open-label, two-parallel groups, phase 2
study to evaluate efficacy and safety of masitinib at 9 mg/kg/day in monotherapy
and combination with dacarbazine in the treatment of patients with
non-resectable or metastatic stage 3 or stage 4 melanoma not carrying a mutation
in the juxta membrane of c-kit.
Patients will be randomized in two groups:
Group 1: Patients will receive masitinib in association with dacarbazine
Group 2: Patients will receive masitinib.
The primary criterion will be the Overall Progression Free Survival (PFS),
defined as the delay between the date of randomisation to the date of documented
progression or any cause of death during the study. Overall Survival will be the
main secondary criterion.
Characteristics of the phase 2 study in stomach cancer
This is prospective, multicentre, open-label, randomised, phase 2 study to
evaluate the efficacy and safety of masitinib in combination with 5-fluorouracil
(5-FU) or capecitabine, or masitinib in combination with irinotecan, or
masitinib in combination with irinotecan, 5-fluorouracil (5-FU) and folinic acid
(FOLFIRI protocol), as second line therapy in patients with gastric or
gastro-oesophageal junction metastatic adenocarcinoma.
Patients will be randomized in three groups:
Group 1: Patients will receive masitinib at 6 mg/kg/day or 9 mg/kg/day, in
association with 5-Fluorouracil or Masitinib at 6 mg/kg/day or 9 mg/kg/day
in association with capecitabine
Group 2: P atients will receive masitinib at 6 mg/kg/day or 9 mg/kg/day, in
association with irinotecan
Group 3: Patients will receive masitinib at 6 mg/kg/day or 9 mg/kg/day in
association with FOLFIRI protocol
The primary criterion will be the Overall Progression Free Survival (PFS),
defined as the delay between the date of randomisation to the date of documented
progression or any cause of death during the study. Overall Survival will be the
main secondary criterion.