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Discover the facts
A late-stage clinical
asset that has completed
10 clinical trials in
colorectal, renal and
prostate cancer
TroVax® has been tested
in over 500 patients,
who have collectively
received over 3,500
doses, and has been
shown to be safe and
extremely well-tolerated
TroVax®
A therapeutic cancer vaccine
Product description
TroVax® is a therapeutic vaccine which stimulates the immune system to destroy
cancerous cells expressing the 5T4 tumour antigen. 5T4 is a surface-expressed protein
which is present on the vast majority of solid tumours and is absent from most essential
normal tissue, which makes it a valuable target for immunotherapy. TroVax® comprises an
attenuated modified vaccinia virus Ankara (MVA), encoding the 5T4 antigen. MVA is the
vaccinia strain of choice because of its excellent safety profile and its effectiveness in
stimulating an immune response against “self” antigens, such as 5T4. TroVax® is
administered via an intramuscular injection.
Anti-5T4
T-cells
TroVax®
5T4
gene
MVA
poxvirus
vector
TroVax®
Tumours
Anti-5T4
antibodies
Immune system response
Clinical status: a Phase II study in hormone refractory prostate cancer generated
encouraging preliminary biomarker data
In October 2012, Oxford BioMedica made a strategic decision to close its US Phase II study
in hormone refractory prostate cancer (HRPC) to focus on investigator-led Phase II
studies. As the HRPC study closed prior to completion of patient recruitment the efficacy
results should be interpreted with caution, however data indicate:
— a trend towards increased time to disease progression in patients who received TroVax®
plus chemotherapy drug docetaxel versus those who received docetaxel alone; and
— prospective validation that Oxford BioMedica’s pre-treatment biomarker can identify
patients most likely to benefit from treatment with TroVax®.
To learn more about
partnering opportunities
for TroVax® please
contact our Business
Development team
[email protected]
Oxford BioMedica plc
Medawar Centre
Robert Robinson Avenue
The Oxford Science Park
Oxford OX4 4GA
Tel: +44 (0)1865 783000
Fax: +44 (0)1865 783001
www.oxfordbiomedica.co.uk
Phase II study in mesothelioma
Oxford BioMedica is collaborating with a team of cancer immunologists led by
Dr Zsuzsanna Tabi at Cardiff University and Dr Jason Lester, an oncologist at Velindre
Cancer Centre in Cardiff, to evaluate TroVax® in a Phase II study in mesothelioma;
a relatively rare form of cancer which affects the tissue lining of the lungs and, less
commonly, the lining of the abdomen. This study is funded by the June Hancock
Mesothelioma Research Fund with TroVax® provided by Oxford BioMedica. The first
patient was treated in March 2013.
Phase II study in colorectal cancer
Oxford BioMedica is collaborating with Cardiff University to evaluate TroVax® in patients
with inoperable metastatic colorectal cancer. The Phase II study, led by Dr Andrew Godkin
at the Department of Infection, Immunity and Biochemistry, is sponsored by Cardiff
University and Oxford BioMedica will provide TroVax®. The first patient was treated in
July 2012.
Other studies
Oxford BioMedica is working with its partners at the UK National Cancer Research
Network (NCRN) in order to develop a Phase II metastatic ovarian cancer protocol.
The Company continues to explore collaborations through clinical networks in order
to generate further data and leverage the value of TroVax®.
Page 1 of 2 Discover the facts: TroVax®
March 2013
Discover the facts
$19.5bn
The cancer targeted therapies
and immunotherapy market was
$19.5 billion in 2009
Clinical proof of concept
Results from nine completed Phase I/II and II trials in colorectal, renal and prostate cancer
in approximately 190 patients have shown that TroVax® is safe, well tolerated and can
be administered in combination with various other treatments. Approximately 90% of
patients treated with TroVax® in these trials mounted an anti-cancer immune response
to the 5T4 antigen.
Oxford BioMedica has also conducted a Phase III trial of TroVax® in advanced and
metastatic renal cell carcinoma, known as TRIST (TroVax® Renal Immunotherapy Survival
Trial). The TRIST trial did not meet the primary endpoint of an increase in patient survival
in the intent to treat patient population. However, exploratory analyses (published in
Clinical Cancer Research in November 2010) identified sub-groups of patients where
TroVax® may be of significant benefit; therefore this trial has provided a valuable
investment in the future clinical development of TroVax®.
TroVax® has been evaluated as a monotherapy and alongside chemotherapy,
cytokine and Tyrosine Kinase Inhibitor (TKI) therapies
Phase Cancer
Type
Trial
I/IIColorectal
Metastatic. Post chemotherapy
IIColorectal
Metastatic. 1st line + 5-Fluorouracil / leukovorin /
irinotecan
Number
of patients1Status
22
Completed
19
Completed
Colorectal
Metastatic. 1st line + 5-Fluorouracil / leukovorin /
oxaliplatin
17
Completed
Colorectal
Metastatic. Adjuvant to liver met surgery
20
Completed
Prostate
Hormone refractory. 2nd line ± granulocyte 27 Completed
macrophage-colony stimulating factor (GM-CSF)
90%
Results from nine completed
Phase I/II and II trials show
that 90% of patients treated
with TroVax® mounted an
anti-cancer immune response
Renal
Metastatic. 1st/2nd line + interferon-alpha (IFN-a)11
Completed
Renal
Metastatic. 1st/2nd line ± IFN-a
Completed
28
Renal
Metastatic. 2nd line + low dose interleukin-2 (IL-2)25
Completed
Renal
Metastatic. 2nd line + high dose IL-2
Completed
28
IIIRenal
Metastatic. 1st line ± IFN-a, IL-2 or sunitinib 733Completed
IIProstate
Hormone refractory. Placebo controlled
80
On-going
Immune responses induced in most patients
Out
of nine Phase I/II and II trials in colorectal, renal and prostate cancer, and one
Phase III trial in renal cell carcinoma, immune responses against 5T4 have been detected
in the majority of patients. Importantly, significant correlations between immune response
and clinical benefit were detected in seven of the nine Phase I/II and II studies. This strong
association between immune response and increased patient survival was confirmed
in the Phase III TRIST trial.
Biomarker development
Further analyses of the Phase III TRIST trial were published in Cancer Immunology,
Immunotherapy in March 2011. Oxford BioMedica has identified an algorithm biomarker for
predicting the quantitative 5T4 antibody response induced by TroVax® in order to identify
those patients who are most likely to mount a strong 5T4 antibody response subsequent to
TroVax® administration. Importantly, the biomarker was also relevant when applied to an
independent dataset derived from the nine historic Phase I and II studies in patients with renal,
colorectal and prostate cancer, which suggests that the biomarker could potentially be applied
to multiple cancer types. The biomarker is a combination of pre-treatment blood parameters,
which can be measured using a simple blood test, including haemoglobin and haematocrit
(the proportion of blood volume occupied by red blood cells). The biomarker will be used in
all future TroVax® clinical trials in order to target a more responsive patient population.
Market opportunity
The oncology market was estimated to be $72 billion in 2010, forecast to grow to
$93 billion in 2015 (source: Datamonitor, 2011). In particular, the cancer targeted therapies
and immunotherapy market was $19.5 billion in 2009, forecast to increase to $36.8 billion
in 2019 (source: Datamonitor, 2010). TroVax® is administered in the same way as most
infectious disease vaccines are given; a simple injection in the arm. If shown to be
efficacious in a pivotal trial for even just one of the major cancers where it is known
that 5T4 is present on the tumours, TroVax® has significant potential.
References:
1. Intent to treat patient population
Key publications:
• Amato et al. Clin Cancer Res; 16(22)
November 15, 2010
• Harrop et al. Cancer Immunol
Immunother. 2011 Jun;60(6):829-37
Page 2 of 2 Discover the facts: TroVax®
March 2013