Jun 6 2012
AB Science SA (Paris:AB) (NYSE Euronext-FR0010557264-AB), a
pharmaceutical company specializing in the research, development and
commercialization of protein kinase inhibitors (PKIs), announces today
that data from the development program of masitinib in gastrointestinal
stromal tumors (GIST) have been presented as part of three presentations
delivered at the American Society of Clinical Oncology (ASCO) 2012
Annual Meeting, 1-5 June in Chicago, Illinois. These presentations were
as follows:
I. Oral presentation "Masitinib mesylate in imatinib-resistant
advanced GIST: A randomized phase II trial" (Abstract #10007,
Sarcoma Oral Abstract Session) was delivered by Professor Adenis on June
4th.
Full abstract available online at: http://abstract.asco.org/AbstView_114_96397.html.
II. Poster presentation "Masitinib in imatinib-naive advanced
gastrointestinal stromal tumor (GIST): Five-year follow-up of the French
Sarcoma Group phase II trial" (Abstract #10089, Sarcoma General
Poster Session), was delivered by Dr Le Cesne on June 3rd.
Full
abstract available online at: http://abstract.asco.org/AbstView_114_96371.html.
III. Poster presentation "Masitinib in comparison to imatinib as
first line therapy of patients with advanced gastrointestinal stromal
tumor (GIST): A randomized phase III trial" (Abstract # TPS10102,
Sarcoma General Poster Session, Trials in progress), was delivered by
Professor Adenis on June 3rd.
Full abstract available online at: http://abstract.asco.org/AbstView_114_96314.html.
Full publication of these ASCO presentation slides will be available
from ASCO's Virtual Meeting website (www.asco.org/vm).
I. Masitinib in second-line treatment of advanced GIST
The oral presentation "Masitinib mesylate in imatinib-resistant advanced
GIST: A randomized phase II trial", delivered by Professor Antoine
Adenis (Centre Oscar Lambret, Lille, France), reported encouraging data
from a phase II study of masitinib in Gleevec®-resistant
gastrointestinal stromal tumors (GIST).
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Masitinib compares favorably to sunitinib in terms of toxicity.
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Masitinib appeared to show good therapeutic benefit in terms of
overall survival.
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According to these preliminary results, a phase III study
(masitinib vs. sunitinib) has been initiated in Europe and the US.
Masitinib significantly improved overall survival in patients with
Gleevec®-resistant GIST as compared to Sutent® (sunitinib) from Pfizer,
which is currently the standard of care for second-line treatment of
GIST. In this study, 44 patients with inoperable, locally advanced or
metastatic GIST and showing disease progression while treated with
Gleevec® (imatinib) (400 to 800 mg/day) received either masitinib (23
patients) at 12 mg/kg/day or sunitinib (21 patients) until progression.
After a median follow-up of 17 months, the updated median overall
survival was not reached for masitinib versus 16 months for sunitinib
(Hazard Ratio: 0.27 [0.09; 0.78]). This is an improvement from the
previous data disclosed after a median follow-up of 14 month, at which
time the Hazard Ratio was: 0.32 [0.11; 0.91]. After 18 months, 82% [59%;
93%] of patients treated with masitinib were still alive, versus 33%
[8%; 62%] for patients treated with sunitinib. Masitinib was well
tolerated, with 17% of patients reporting non-hematological grade 3
related adverse events, as compared with 62% of patients in the
sunitinib treatment-arm. No patients receiving masitinib reported any
related serious adverse events compared with 19% of patients in the
sunitinib treatment-arm.
A phase III study has been initiated in this indication on the basis of
these results, with recruitment of the first patient announced on 15th
May 2012. This is a phase III, multicenter, randomized, open-label,
controlled, two-parallel group study evaluating the efficacy and safety
of masitinib as compared with sunitinib (Sutent®) in GIST patients after
progression under imatinib (Gleevec®). This study will recruit around
200 patients from 50 sites around the world, randomized with a 1:1 ratio
between masitinib and sunitinib. The primary end-point is overall
survival.
II. Masitinib as first-line treatment of advanced GIST
Two other presentations were also delivered, one reporting on the 5-year
follow-up data from a phase II clinical study of masitinib in the
first-line treatment of locally advanced or metastatic GIST, and a
related presentation describing the ongoing phase III study for this
indication.
The poster communication "Masitinib in imatinib-naive advanced
gastrointestinal stromal tumor (GIST): Five-year follow-up of the French
Sarcoma Group phase II trial", delivered by Dr Axel Le Cesne (Institut
Gustave Roussy, Villejuif, France), reported on the latest data from a
multicenter, open label, phase II study, evaluating efficacy and safety
of masitinib as a first-line treatment of advanced GIST.
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5-year follow-up data substantiates that masitinib has an effective
and sustainable activity in imatinib-naïve GIST patients.
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Median overall survival in masitinib compares favorably to that of
imatinib especially in patients with KIT exon 11 mutation
subpopulation.
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Adverse events occurred mainly during the first year, with good
long term tolerance experienced thereafter.
With a median follow-up of 72 months, the updated overall survival data
for the KIT exon 11 mutation subpopulation>
III. About the phase III study in Gleevec®-naïve GIST
(first-line) - trial in progress
The poster communication "Masitinib in comparison to imatinib as first
line therapy of patients with advanced gastrointestinal stromal tumor
(GIST): A randomized phase III trial", delivered by Professor Antoine
Adenis (Centre Oscar Lambret, Lille, France), reported on the progress
and characteristics of this phase III study.
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Considering the promising long term efficacy observed in survival
and safety from phase II, there is a compelling motive to perform a
head-to-head comparison of masitinib against imatinib in first-line
setting.
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On May 11th 2012, an Independent Data Monitoring Committee gave its
positive opinion to continue this study.
This prospective, multicenter, randomized, open-label,
active-controlled, 2-parallel group, phase III study compares efficacy
and safety of masitinib (7.5 mg/kg/day) to the active control of
imatinib (400 or 600 mg/day) in first-line treatment of patients with
advanced GIST. This study will recruit around 200 patients from sites
around the world, randomized with a 1:1 ratio between masitinib and
imatinib. The primary endpoint is progression free survival, defined as
the delay between the date of randomization to the date of documented
progression or any cause of death during the study. Overall survival
will be the main secondary endpoint.
