Results from 3 Phase II Trial
Oxford Biomedica PLC
02 March 2005
FOR IMMEDIATE RELEASE 2 MARCH 2005
OXFORD BIOMEDICA ANNOUNCES ENCOURAGING RESULTS FROM THREE PHASE II TRIALS OF
TROVAX IN PATIENTS WITH COLORECTAL CANCER
Oxford, UK - 2 March 2005: Oxford BioMedica (LSE: OXB), the leading gene therapy
company, today announces encouraging results from three ongoing Phase II trials
of TroVax, its lead cancer immunotherapy, in the treatment of metastatic
colorectal cancer.
Highlights of the Phase II trial results:
• In two trials in the first line setting in combination
with chemotherapy:
o 25 patients are evaluable for immunological responses
o 19 patients are evaluable for tumour responses (tumour stabilisation
and tumour shrinkage)
o The primary endpoints of safety and immunological responses have been
achieved
o The secondary endpoint of clinical benefit has exceeded expectation
o The immune response rate was exceptionally high. All 25 patients
mounted immune responses to the 5T4 tumour antigen
o The tumour response rate was better than expected. Eighteen of 19
patients responded to treatment (three complete responses, ten partial
responses and five disease stabilisations)
o Chemotherapy did not affect the frequency of immune responses compared
to the Phase I/II trials in second line treatment
• In Cancer Research UK's trial in the (neo) adjuvant to
surgery setting, all eight evaluable patients mounted immune responses
• In all three trials, TroVax has an excellent safety
profile to date. No serious adverse events were attributed to the product
New data from two trials in first line treatment of metastatic colorectal cancer
with concomitant chemotherapy have confirmed previous indications that the
primary endpoints of safety and immunological responses have been achieved. All
patients that have reached the interim stage of the trial have shown an immune
response to the 5T4 tumour antigen.
Today, the Company is also reporting that, in the two trials, the secondary
endpoint of clinical benefit has exceeded expectation. Eighteen of 19 evaluable
patients responded to treatment. Whilst five patients had disease stabilisation
following treatment, 13 of the 19 patients were defined as clinical responders
according to industry standard criteria. These comprised three complete (total
tumour shrinkage) responders and ten partial (more than 30 per cent tumour
shrinkage) responders.
In addition, analysis of the first evaluable patients in a third Phase II trial
of TroVax in colorectal cancer patients undergoing surgery for liver metastases
has shown that all patients have mounted an immune response against the target
tumour antigen. This investigator initiated trial is sponsored by Cancer
Research UK.
The results from the earlier Phase I/II studies showed a highly significant
correlation between patients' immune response to TroVax and time to disease
progression, which translated into a correlation with improved overall survival.
Data emerging from the Phase II trials suggest that the magnitude and duration
of immune responses may be even greater in first line treatment with concomitant
chemotherapy and in the (neo) adjuvant setting with surgery. The new data
reported today provide further evidence that TroVax may offer potential benefit
to patients with colorectal cancer.
Commenting on the Phase II results with TroVax in colorectal cancer, Professor
Alan Kingsman, Chief Executive of Oxford BioMedica, said: 'We are very pleased
with the progress of these three Phase II trials of TroVax in colorectal cancer.
The high frequency of anti-5T4 responses in patients confirms the immunological
effectiveness of TroVax and the preliminary clinical response data look
promising. Based on current data, we are optimistic that TroVax will have a role
to play in the treatment of cancer and we look forward to testing this in
pivotal clinical studies.'
Commenting on Cancer Research UK's initial Phase II results with TroVax in the
adjuvant setting, Dr. Sally Burtles, Director of Drug Development of Cancer
Research UK said: 'We are delighted that the vaccine has stimulated an immune
response to 5T4 in all of the evaluable patients to date. Further trials will be
needed to find out if this translates into clinical benefit for patients.'
Phase II trials of TroVax plus chemotherapy in first line treatment
Oxford BioMedica initiated two open label Phase II trials in first line
treatment of metastatic colorectal cancer in 2003. The two trials were designed
to investigate whether concomitant chemotherapy affected patients' immune
responses to TroVax. Enrolment in both trials (TroVax plus IFL and TroVax plus
FOLFOX) was completed in September 2004. The recruitment objective was to have
ten evaluable patients in each trial. The primary endpoints were safety and
demonstrable immune responses to the 5T4 tumour antigen.
On 1 September 2004, the Company reported that the primary endpoints were likely
to be achieved based on preliminary data from 13 patients who had reached the
interim analysis point, defined as four TroVax immunisations and more than eight
cycles of chemotherapy. Of these patients, 11 (85 per cent) had mounted antibody
and/or cellular anti-5T4 immune responses.
These encouraging results have been confirmed as the trials have progressed. To
date, 25 patients have been assessed at the interim stage of the trial. There
have been no serious adverse events attributed to TroVax treatment and the
number of patients mounting an immune response has risen to 100 per cent with
all 25 patients showing antibody and/or cellular responses to the tumour
antigen.
Furthermore, 19 patients have been assessed for tumour responses (tumour
stabilisation and tumour shrinkage), having received at least three TroVax
immunisations and one or more computed tomography scans. Patients entered the
trial with progressive disease, and 18 of 19 patients had a tumour response
following treatment. Thirteen of 19 patients were classified as clinical
responders, comprising three complete and ten partial responses.
Two independent studies of the chemotherapy regimens alone reported clinical
response rates in evaluable patients of 41 and 50 per cent* respectively
(Douillard et al., The Lancet 2000, vol 355, pp 1041-1047; de Gramont et al.,
Journal of Clinical Immunology 2000, vol 18, pp2938 -2947). However, a precise
comparison with the TroVax trials is not possible owing to differences in the
trial protocols and patient numbers.
Data from the two Phase II trials of TroVax will be presented at the American
Society of Clinical Oncology (ASCO) meeting in Orlando, USA, in May 2005. The
trials are on track to report full safety and immunological data as well as
final tumour response statistics in the second half of 2005. Patient survival,
which can be compared to historical controls, will be reported once the median
survival has been reached in the two trials. This is anticipated towards the end
of 2005.
A more detailed report of these two trials of TroVax with first line
chemotherapy is set out below:
(i) TroVax plus IFL chemotherapy
In the trial of TroVax plus irinotecan, 5-flourouracil and leucovorin, a
chemotherapy combination known as IFL, 19 patients have been recruited. The
treatment regimen comprises six immunisations of TroVax and up to 12 cycles of
chemotherapy. 13 patients have reached the preliminary analysis stage, and all
13 have mounted anti-5T4 immune responses.
Clinical and tumour responses have been assessed in 11 patients that have
received four TroVax immunisations and completed chemotherapy treatment. Ten of
11 patients responded to treatment. Three patients had stable disease, while
seven patients (64 per cent*) mounted clinical responses, comprising one
complete response and six partial responses. For reference, the two-arm pivotal
trial that supported approval of IFL chemotherapy alone in first line treatment
of metastatic colorectal cancer, in a total of 338 patients, showed a clinical
response rate of 41 per cent* for the evaluable IFL group (Douillard et al.,
2000).
(ii) TroVax plus FOLFOX chemotherapy
The TroVax plus FOLFOX trial has recruited 17 patients, similarly receiving six
immunisations of TroVax alongside chemotherapy. The current status is that 12
patients have reached the preliminary stage for immunological analysis and eight
patients are evaluable for tumour responses. At the preliminary stage of four
TroVax immunisations and eight cycles of chemotherapy, all 12 patients have
mounted anti-5T4 immune responses.
Clinical responses were observed in six of the eight (75 per cent*) presently
evaluable patients, comprising two complete responses and four partial
responses. The two other evaluable patients experienced disease stabilisation
following treatment, meaning that 100 per cent of evaluable patients responded
to treatment. An independent two-arm trial with a comparable FOLFOX chemotherapy
regimen and enrolment criteria, reported a confirmed clinical response rate of
50 per cent* and a tumour response rate, which includes disease stabilisation,
of 82 per cent in a total of 420 patients (de Gramont et al., 2000).
Phase II trial of TroVax in patients undergoing surgery for resectable liver
metastases
An investigator initiated, open label Phase II trial started in 2004, with
sponsorship from Cancer Research UK, in colorectal cancer patients who have
operable liver metastases. Patients receive TroVax immunisations before
(neoadjuvant) and after (adjuvant) surgery. Recruitment into this 20-patient
trial is over halfway completed.
Eleven patients have received the initial regimen of TroVax immunisations, two
of which were subsequently withdrawn for being ineligible for surgery. The eight
evaluable patients have achieved the primary endpoint of immune responses to the
5T4 tumour antigen, and are eligible for further TroVax doses. The most recent
patient has not progressed far enough through the trial to assess immune
responsiveness. TroVax has been safe and well tolerated in all patients treated
to date in this trial.
The treatment schedule comprises two immunisations with TroVax before and after
liver surgery and, potentially, a further two vaccinations. The endpoints of the
study are safety, immunological responses to 5T4 and clinical benefit. Following
surgery, these patients have a lower tumour burden and longer survival
expectation than patients in Oxford BioMedica's other Phase II trials in
colorectal cancer. This potentially makes them even more responsive to
immunotherapy approaches such as TroVax. Patients are generally not given
chemotherapy following liver surgery and there is a need for safe and effective
treatments to help prevent disease relapse.
Full results from this Phase II trial of TroVax in the (neo) adjuvant setting of
colorectal cancer treatment will be published in an appropriate clinical journal
by Cancer Research UK once the study is completed.
Conclusion
More than 65 patients with colorectal cancer have been treated with TroVax to
date in four clinical trials. Across all the trials, the safety profile of
TroVax has been excellent and the majority (98 per cent) of assessable patients
(50 patients) have mounted immune responses following treatment with TroVax.
This is an exceptionally high response rate in the context of clinical studies
with other cancer vaccines (Mocellin et al., Lancet Oncology 2004; vol 5:
681-9). TroVax has been investigated in different settings in these trials -
first line treatment with chemotherapy, second line treatment and the (neo)
adjuvant setting with surgery - and achieved its primary endpoints in each
setting.
These data suggest that TroVax has therapeutic potential across all stages of
colorectal cancer, supporting the notion that the product may reach large
markets in this indication.
The Company and its clinical advisors are refining a strategy to achieve
potential product registration of TroVax in 2008-09. This will provide Oxford
BioMedica and its potential partners with a clear and rapid route to product
commercialisation.
Other TroVax trials
In addition to the three ongoing Phase II trials in colorectal cancer, Oxford
BioMedica is expanding the opportunity for TroVax to other tumour types. The
Company believes that metastatic renal cell carcinoma (RCC) offers an attractive
commercial opportunity for the development of TroVax. Studies show that the 5T4
antigen is present on over 90 per cent of RCC samples; current treatment options
are ineffective or have serious side effects; and TroVax could benefit from
orphan drug and fast track designations in this indication.
A Phase II trial in RCC with TroVax alongside high dose interleukin-2 is
underway in the United States. Preliminary immunology data are expected around
mid-2005. In breast cancer, the Southwest Oncology Group, which is a US clinical
trials consortium, is expected to start a Phase II trial in late stage patients,
in 2005.
-Ends-
* Clinical response data from Oxford BioMedica's Phase II trials are unaudited.
They are based on patients that are evaluable and use the industry standard
Response Evaluation Criteria in Solid Tumours (RECIST). The data from the trials
of the chemotherapy agents alone, cited in this press release, are derived from
evaluable patients, using clinical response criteria set by the World Health
Organisation (WHO). The criteria defined by RECIST and WHO are similar but not
identical.
A telephone conference for analysts, to discuss today's announcement, will be
held at 12:00pm today. Professor Alan Kingsman, CEO, will host the call. A
presentation of the trial data will be available on the Company's website from
11:30am. http://www.oxfordbiomedica.co.uk/
Conference call dial-in details are available from Buchanan Communications.
Please contact Mary-Jane Johnson on telephone no. 020 7466 5000.
For further information, please contact:
Oxford BioMedica plc:
Professor Alan Kingsman, Chief Executive Tel: +44 (0)1865 783 000
Nick Woolf, SVP Corporate Strategy
City/Financial Enquiries:
Lisa Baderoon/ Mark Court/ Mary-Jane Johnson Buchanan Tel: +44 (0)20 7466 5000
Communications
Scientific/Trade Press Enquiries:
Sue Charles/ Katja Stout/ Ashley Lilly Tel: +44 (0)20 7886 8150
Northbank Communications
CR-UK Contact Details:
Steve Palmer Tel: +44 (0)20 7061 8312
Notes to editors
1. Oxford BioMedica
Oxford BioMedica (LSE: OXB) is a biopharmaceutical company specialising in the
development of novel gene-based therapeutics with a focus on the areas of
oncology and neurotherapy. The Company was established in 1995 as a spin out
from Oxford University, and is listed on the London Stock Exchange.
Oxford BioMedica has core expertise in gene delivery, as well as in-house
clinical, regulatory and manufacturing know-how. In oncology, the pipeline
includes an immunotherapy and a gene therapy in multiple Phase II trials, and a
preclinical targeted antibody therapy in collaboration with Wyeth. In
neurotherapy, the Company's lead product is a gene therapy for Parkinson's
disease, which is expected to enter clinical development in 2005, and four
further preclinical candidates. The Company is underpinned by over 80 patent
families, which represent one of the broadest patent estates in the field.
The Company has a staff of approximately 65 split between its main facilities in
Oxford and its wholly owned subsidiary, BioMedica Inc, in San Diego, California.
Oxford BioMedica has corporate collaborations with Wyeth, Intervet, Amersham,
Viragen, MolMed and Kiadis; and has licensed technology to a number of companies
including Merck & Co and Biogen Idec.
Further information is available at www.oxfordbiomedica.co.uk.
2. TroVax(R) cancer immunotherapy
TroVax is Oxford BioMedica's leading cancer immunotherapy product. It is
designed specifically to stimulate an anti-cancer immune response and has
potential application in most solid tumour types. TroVax targets the tumour
antigen 5T4, which is broadly distributed throughout a wide range of solid
tumours. The presence of 5T4 is correlated with poor prognosis. The product
consists of a poxvirus (MVA) gene transfer system, which delivers the gene for
5T4 and stimulates a patient's body to produce an anti-5T4 immune response. This
immune response destroys tumour cells carrying the 5T4 protein.
Two Phase I/II trials with TroVax have been completed in the UK in late stage
colorectal cancer patients. The results showed that the product is safe; that
patients mount an anti-5T4 immune response; and that the immune response
correlates, with high significance, to time to disease progression, which
translates into a correlation with improved overall survival.
Four Phase II trials are underway. The trials are investigating TroVax in
colorectal cancer in combination with first line standard of care treatment and
as a (neo) adjuvant to surgery; and in renal cell carcinoma. The US Southwest
Oncology Group is planning an additional Phase II trial in breast cancer.
3. Colorectal cancer
Every year, about one million new cases of colorectal cancer are diagnosed
worldwide. It is the second leading cause of cancer death in the US and the
third most frequently diagnosed cancer, according to the American Cancer
Society. More than 56,000 people die from colorectal cancer in the US each year
and about 94,000 people in Europe.
Colorectal cancer begins in the cells that line the colon or rectum. Colorectal
cancer staging describes how advanced the cancer is. The most severe is Stage
IV, which defines cancers that have spread to other parts of the body such as
the liver or lungs.
In the US, the current standard of care for first line treatment of Stage IV
colorectal cancer is the chemotherapy combination of irinotecan, 5-fluorouracil
(5FU) and leucovorin, a combination known as IFL. In Europe, the most common
treatment is oxaliplatin, 5FU and leucovorin, a combination referred to as
FOLFOX. The leading branded products are Pfizer's Camptosar(R)/Campto(R)
(irinotecan) and Sanofi-Aventis' EloxatinTM (oxaliplatin). Combined sales of
these products exceeded $2.1 billion in 2004.
A new first line treatment option received approval from the US FDA in February
2004. The product, AvastinTM (bevacizumab) from Genentech and Roche is a
therapeutic antibody deigned to inhibit vascular endothelial growth factor, a
protein that plays a role in tumour angiogenesis and maintenance of existing
tumour vessels. Avastin is approved for use in combination with 5FU based
chemotherapy regimens, including both IFL and FOLFOX. First year sales of
Avastin in 2004 were $554 million.
Despite the improvements in treatment, the available options remain
unsatisfactory to colorectal cancer patients, and there is a need for new
therapies offering improved efficacy, tolerability and convenience.
4. Cancer Research UK
Cancer Research UK's vision is to conquer cancer through world-class research.
The charity works alone and in partnership with others to carry out research
into the biology and causes of cancer, to develop effective treatments, improve
the quality of life for cancer patients, reduce the number of people getting
cancer and to provide authoritative information on cancer. Cancer Research UK is
the world's leading independent charity dedicated to research on the causes,
treatment and prevention of cancer.
For further information about Cancer Research UK's work or to find out how to
support the charity, please call +44 (0)20 7009 8820 or visit http://
www.cancerresearchuk.org/
This information is provided by RNS
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