Transgene’s Therapeutic Vaccine TG4010 Meets Primary Endpoint Non-small Cell Lung Cancer Phase IIb Trial
STRASBOURG, France, June 2nd, 2008 - Transgene (Euronext Paris:
FR0005175080) today announced the successful results of the Phase
IIb trial evaluating its therapeutic vaccine TG4010 (MVA-MUC1-IL2)
as an adjunct to first line chemotherapy in patients with advanced
non-small cell lung cancer (NSCLC). These results will be presented
today at the 2008 annual meeting of the American Society of
Clinical Oncology in Chicago.
“We are very pleased that the data accumulated from the Phase
IIb trial of our therapeutic vaccine TG4010 confirm the results we
have previously observed in this indication and establish that the
trial has met its primary endpoint”, said Philippe Archinard,
Chief Executive Officer of Transgene. “These results clearly
warrant pursuing development into a Phase III program and we will
be seeking to establish a partnership in order to complete the last
stages of clinical development and bring TG4010 to the
market.”
The Phase IIb trial is a randomized, open label and controlled
study designed to assess the efficacy of TG4010 in combination with
cisplatin and gemcitabine compared to the chemotherapy regimen
alone. The trial completed the enrolment of 148 patients at the end
of May 2007 and was conducted in 27 centres located in France,
Poland, Germany, and Hungary. The patients had NSCLC of all
histology types including squamous cell carcinoma expressing MUC1,
either stage IIIB with effusion (8%) or stage IV (92%), and had not
received prior systemic treatment for their advanced disease. Half
of the patients were randomized to receive the combination regimen
of TG4010 vaccine plus chemotherapy (experimental arm). The other
half of the patients received chemotherapy alone (control arm). The
statistical primary endpoint is to observe at least 40% of patients
free of progression six months after randomization in the
experimental arm. Secondary endpoints are response rate, time to
progression, overall survival, safety, immunological responses,
proteomics, transcriptomics and genomics.
The trial met its primary endpoint, with a progression-free
survival (PFS) at six months of 44% (33 / 74 patients) in the
experimental arm. In the control arm, PFS at six months is 35% (26
/ 74 patients).
Additionally, the response rate is substantially higher for the
combination of TG4010 with chemotherapy compared to the
chemotherapy alone. The response rates are 43% (32 / 74 patients)
in the experimental arm and 27% (20 / 74 patients) in the control
arm. The difference in favour of the experimental arm is
statistically significant (p=0.03). Tumour responses were evaluated
by an independent central review committee.
Time to progression is 5.8 months in the experimental arm and 5.2
months in the control arm. Median survival is 10.7 months for the
experimental arm and 10.3 months for the control arm. Overall
survival data is not yet mature. However, a trend for long-term
survival is being observed in the experimental arm: after a
follow-up of 13 months, 43% of the patients are still alive in the
TG4010 plus chemotherapy arm compared to 33% in the control arm.
Extended overall survival data will be available by the the end of
the year.
A large biomarker exploratory program (immunology, proteomics,
transcriptomics and genomics) is in progress to further
characterize TG4010’s mode of action and contribute to the
design of Phase III trials. Preliminary results show that in
patients without elevated blood level of activated NK cells
(“Natural Killers”, a group of cytotoxic lymphocytes)
at baseline, i.e. 101 out of 138 evaluable patients, the median
survival is 15.6 months in the experimental arm and 10.7 months in
the control arm. Complete biomarker results should be available by
the fourth quarter of 2008.
The trial confirmed the favourable safety profile of TG4010 when
associated with chemotherapy: most adverse events observed so far
were considered related to chemotherapy as well as to the
underlying disease. Hematological toxicity was equivalent in both
treatment groups. Most frequent adverse events related to TG4010
were injection site reactions and fever, which are classic
vaccine-associated reactions.
About TG4010 cancer vaccine
TG4010 (MVA-MUC1-IL2) uses the Modified Vaccinia Ankara virus
vector, a poxvirus that combines distinguishing advantages for an
optimized systemic vaccination:
· MVA is a highly attenuated strain which has been tested
extensively in humans as a smallpox vaccine and is known to
strongly stimulate innate and adaptive immune responses to
antigens.
· MUC1 is a major tumor-associated antigen that provides a
viable target for vaccination.
· TG4010 expresses the entire MUC1 gene sequence and has the
potential to generate an immune response to all antigenic epitopes
of MUC1.
· The sequence coding for the cytokine Interleukin 2 (IL2)
is included to help stimulate specific T-cell response.
About the Phase IIb results presentation at ASCO 2008
The poster presentation and discussion will take on June 2nd, 2008
at the annual meeting of the American Society of Clinical Oncology,
in Chicago (Abstract Nr. 8023, First author: Rodryg Ramlau, MD,
PhD, Regional Lung Disease Hospital, Poznan, Poland). The poster is
available on Transgene’s website (www.transgene.fr).
About previous TG4010 clinical data in NSCLC
Previous Phase IIa data are available at:
http://www.transgene.fr/us/pdf/communique_presse/communiques_divers_2005/PR-US_17-
05-2005_ASCO_POUMON.pdf
About Transgene
Transgene is a France-based biopharmaceutical company dedicated to
the development of therapeutic vaccines and immunotherapeutic
products in oncology and infectious diseases. The company has one
product which has completed Phase II trials (TG4001/R3484), two
compounds in Phase II trials (TG4010 and TG1042) and one compound
in Phase I studies (TG4040). Transgene has concluded a strategic
partnership agreement with Roche for the development of its
TG4001/R3484 therapeutic vaccine to treat HPV-mediated diseases.
Transgene has bio-manufacturing capacities for viral-based vectors
and technologies available for out-licensing. Additional
information about Transgene is available on the Internet at
www.transgene.fr.
Cautionary note regarding forward-looking statements
This press release contains forward-looking statements referring to
seeking a partnership for and
further developing one of Transgene’s therapeutic vaccine
candidates. However, establishing a
partnership and successfully pursuing product testing and
development depend on a variety of factors,
including identifying an appropriate partner, agreeing on financial
and other partnership terms, and
the technical performance of the product candidate in further
testing. Results from future studies with
more data may show less favourable outcomes than prior studies, and
there is no certainty that
product candidates will ever demonstrate adequate therapeutic
efficacy or achieve regulatory
approval or commercial use. For further information on the risks
and uncertainties involved in the
testing and development of Transgene’s product candidates,
see Trangene’s Document de référence
on file with the French Autorité des marchés
financiers on its website at http://www.amf-france.org
and Transgene’s website at http://www.transgene.fr .
Posted: June 2008
