OXFORD BIOMEDICA REPORTS NEW ENCOURAGING
PHASE II RESULTS WITH TROVAX® AND PROGRESS IN THE DEVELOPMENT
PLAN
-
Phase II Results at American Society of Clinical Oncology
Annual Meeting -
View
Abstracts (87kb)
View Posters (296kb)
Oxford BioMedica
(LSE: OXB), a leading gene therapy company, reported today that encouraging
data from five Phase II studies of TroVax, its lead cancer immunotherapy
product, were presented at the Annual Meeting of the American Society
of Clinical Oncology (ASCO). In addition, the Company provided an update
on the clinical development plan for TroVax, which is progressing towards
the start of Phase III trials in renal and colorectal cancer.
New Phase II results reported at ASCO:
- Updated analysis of unaudited tumour response data from
two trials of TroVax plus chemotherapy in metastatic colorectal
cancer showed that 95% of per protocol patients had disease control.
- Updated survival data from the two metastatic colorectal
cancer trials showed that a third of the patients were
still alive with an average follow-up time of more than two years.
- Data from
Cancer Research UK’s trial of TroVax adjuvant
therapy in colorectal cancer patients undergoing
surgery for liver
metastases showed that 96% of patients produced
an anti-tumour immune response and
56% of operable patients remained disease-free
after nine months of follow-up.
- First presentation of data from two studies of TroVax plus
interleukin-2 in renal cell carcinoma showed that two of
the first six evaluable patients (33%) had partial responses. If reproduced in
a larger
study this would compare favourably with a response rate
of 10% for interleukin-2 alone.
Development plan update:
- QUASAR, a UK-based clinical trial network, has agreed to
develop a Phase III trial of TroVax in approximately 3,000
patients with early stage colorectal cancer and the study will be submitted to
the appropriate
funding agencies.
- Phase III TRIST study in renal cell carcinoma is on course
to start in the second half of 2006. Clinical Trial Applications
are being filed in European countries as part of the implementation of the protocol,
for which a Special Protocol Assessment was recently agreed
with the FDA.
- Three further, small Phase II studies are starting in renal
cell carcinoma, evaluating TroVax in combination with interferon-a
and sunitinib.
- Recruitment is proceeding rapidly in the recently announced
Phase II study of TroVax with GM-CSF in 24 patients with
hormone refractory prostate cancer. Eleven patients have already been recruited.
Commenting on the
Phase II results and progress on the development plan,
Oxford BioMedica’s
Chief Medical Officer, Dr Mike McDonald, said: “We
are very pleased that the positive results from the Phase
II colorectal cancer trials continue to be mirrored in
renal cancer. There is growing
interest in TroVax amongst the clinical community in both
Europe and the USA. This external support has enabled
us to broaden the clinical development
of TroVax.”
On the approval by
the QUASAR group of the proposed Phase III trial of TroVax,
the Chairman of QUASAR
and Head of Clinical Pharmacology at the
University of Oxford, Professor David Kerr, said: “The QUASAR
group is committed to the Phase III trial of TroVax in early
stage colorectal cancer. We must now secure the necessary
grant funding to start this important
trial and potentially provide a novel therapy for this
large patient group where treatment options have evolved
little in recent years.”
Oxford BioMedica’s
Chief Executive Officer, Professor Alan Kingsman added: “These new clinical results further illustrate the potential
for TroVax to treat different cancers at different stages
of disease and support our strategy of advancing to larger
and pivotal registration trials.
We look forward to starting our Phase III TRIST trial of
TroVax in renal cancer later this year and working with
both QUASAR and commercial partners
on the design and initiation of additional trials in colorectal
cancer.”
Phase II results of TroVax plus chemotherapy in colorectal cancer
Oxford BioMedica has completed two Phase II trials of TroVax
in first-line
treatment of metastatic colorectal cancer alongside two
standard of care chemotherapy
regimens: irinotecan, 5-fluorouracil
and
leucovorin (IFL) and Commenting on the Phase II results
and progress on the development plan, Oxford BioMedica’s Chief
Medical Officer, Dr Mike McDonald, said: “We
are very pleased that the positive results from the Phase
II colorectal cancer trials continue to be mirrored in
renal cancer. There is growing
interest in TroVax amongst the clinical community in both
Europe and the USA. This external support has enabled
us to broaden the clinical development
of TroVax.”
On the approval by
the QUASAR group of the proposed Phase III trial of TroVax,
the Chairman of QUASAR
and Head of Clinical Pharmacology at the
University of Oxford, Professor David Kerr, said: “The QUASAR
group is committed to the Phase III trial of TroVax in early
stage colorectal cancer. We must now secure the necessary
grant funding to start this important
trial and potentially provide a novel therapy for this
large patient group where treatment options have evolved
little in recent years.”
Oxford BioMedica’s
Chief Executive Officer, Professor Alan Kingsman added: “These new clinical results further illustrate the potential
for TroVax to treat different cancers at different stages
of disease and support our strategy of advancing to larger
and pivotal registration trials.
We look forward to starting our Phase III TRIST trial of
TroVax in renal cancer later this year and working with
both QUASAR and commercial partners
on the design and initiation of additional trials in colorectal
cancer.”
Phase
II results of TroVax plus chemotherapy in colorectal cancer
Oxford BioMedica has
completed two Phase II trials of TroVax in first-line treatment
of metastatic colorectal cancer
alongside two standard of care chemotherapy regimens:
irinotecan, 5-fluorouracil and
leucovorin (IFL) and oxaliplatin,
5-fluorouracil and leucovorin (FOLFOX). The two single-arm,
open-label trials enrolled a total of 36 patients. On
6 June 2006 at the
ASCO meeting, the Company presented final safety and immunology
data including new details of the cytotoxic T-cell response,
efficacy results including
an update on both tumour responses and survival, and also
analysis of the relationship between the magnitude of
immune responses and clinical benefit.
As reported previously, the primary endpoints of safety and anti-tumour
immunological responses were achieved and the results confirmed the excellent
safety profile of TroVax with no serious adverse events being attributed
to the product. All 23 per protocol patients (=3 TroVax immunisations
and =6 chemotherapy cycles) across the two trials mounted an anti-tumour
immune response. Immune responses were higher than in the Phase I/II study
and cytotoxic T-lymphocyte (CD8+) levels were exceptionally high, reaching
frequencies of 1 per 1000 peripheral blood mononuclear cells. Such high
levels are normally only seen in infectious diseases where the CD8+ response
frequently clears the infection.
Clinical benefit exceeded
the Company’s expectation based on previously
reported data for chemotherapy alone. Based on updated, unaudited computerised
tomography (CT) scans, 95% of per protocol patients showed disease control,
which is higher than the previously reported figure of 91%: 17% had complete
responses; 43% had partial responses; and 35% had stable disease. In the
TroVax plus FOLFOX trial, there was a statistically significant (p <0.02)
correlation between patients’ 5T4-specific immune response and their
tumour response.
The Company also presented updated survival information for the two studies.
However, it should be noted that patient numbers are too small to provide
a rigorous conclusion and comparisons with historical data can be unreliable.
In the modified intent to treat group (=2 TroVax immunisations) of 30
patients, TroVax extended median survival from 72 weeks to 80 weeks and
improved survival at twelve months from 70% to 90%. Importantly, as at
10 May 2006, ten of the 30 patients remained alive with an average follow-up
time of more than two years. The Company regards these data as encouraging
and believe that, if these observations were reproduced in a pivotal study,
they would be sufficient to support product registration.
Phase II results of TroVax adjuvant therapy in colorectal cancer:
Clinicians from the Christie Hospital and Paterson Institute
for Cancer Research, both of Manchester, UK, have completed
enrolment of a Phase II trial of TroVax in colorectal cancer patients
who have
operable liver metastases. The single-arm, open-label
trial, which enrolled 20 patients, is sponsored by Cancer Research UK.
Patients received TroVax
immunisations before surgery (neoadjuvant) and after
surgery (adjuvant). On 4 June 2006 at the ASCO meeting, the Principal
Investigators for the trial presented safety and immunological data,
and clinical outcomes from patient follow-up.
The primary objective of the trial was to investigate the immunological
responses to TroVax during potentially curative surgery for colorectal
cancer liver metastases. The group of patients selected for the trial
had good performance status, but patients often have micro-metastatic
disease that persists post-operatively. TroVax could provide a safe and
effective treatment option for these patients that have a low but metastatic
tumour burden.
TroVax was well tolerated in all patients with no serious
adverse events associated with the product. Of the 20
patients recruited, 16 had successful surgical resection
of their colorectal cancer liver metastases. All evaluable
resected tumours were positive for the 5T4 antigen, the
target for TroVax.
The primary endpoint
of immunological response was achieved. In the intent
to treat population, 19 of the 20 patients (95%) mounted
anti-tumour immune responses against 5T4. Four patients
were withdrawn
for incorrect diagnosis
or inoperable cancer. Clinical analysis was conducted
on the remaining 16 evaluable patients. At a median follow-up
of 9.1 months, nine of these
16 patients (56%) remained disease-free. Oxford BioMedica
is encouraged by the data to date from Cancer Research
UK’s trial
of TroVax in this setting of adjuvant therapy to surgery for
liver metastases.
Preliminary Phase II results of TroVax plus interleukin-2 (IL-2) in renal
cell carcinoma
Two Phase II trials of TroVax with either high dose or
low dose IL-2 are ongoing in the USA. The trials are designed to gather
information on the safety of the combination treatments as well as on
immune responses to the 5T4 tumour antigen. Results from the two trials
were published in the ASCO Proceedings for the Annual Meeting.
To date, 27 of 50 patients have been recruited into the two trials. There
have been no serious adverse events related to TroVax, which is consistent
with the excellent safety profile of the product across all trials, and
TroVax treatment was well tolerated. Across both trials, 15 of 17 evaluable
(=3 TroVax immunisations) patients (88%) have shown anti-tumour antibody
responses to 5T4. The antibody levels were at the top end of the range
reported from the Phase II trials with TroVax in patients with colorectal
cancer undergoing chemotherapy. Analysis of cytotoxic T-lymphocyte responses
is in progress.
To date, unaudited CT scans are available for the first six patients.
Of these, two (33%) have shown partial responses based on industry-standard
criteria known as Response Evaluation Criteria in Solid Tumours (RECIST).
According to the literature, IL-2 is usually associated with a clinical
response rate of only 10% in this patient group.
The Company and the
Principal Investigators for these trials are encouraged
by the frequency of clinical responses with TroVax,
albeit
in a small number of patients at this stage. These data
endorse the Company’s
strategy to initiate the Phase III TRIST trial, which
includes TroVax alongside low dose IL-2.y
Development plan update:
(i) Renal cell carcinoma (RCC)
The Company is expanding its
Phase II programme in RCC with three additional single-arm,
open-label Phase II studies
to assess TroVax in combination with either interferon-alpha
(IFNa) or sunitinib
(Sutent®). These small trials are designed to broaden the clinical
experience with TroVax and provide further support for the planned Phase
III TRIST trial that will use IFN-a and Sutent®, in addition to IL-2,
as standard of care treatments. Enrolment has commenced
in the first of these studies, which are being conducted
in centres in the UK and the
USA.
The Company’s
multi-centre, randomised, double-blind, placebo-controlled
700-patient Phase III trial, TRIST (TroVax Renal
Immunotherapy
Survival Trial), is on-track to commence recruitment in
the second half of 2006.
The manufacture of the trial material is largely complete.
Oxford BioMedica secured an agreement with the US Food
and Drug Administration (FDA) on
a Special Protocol Assessment in May 2006 and Clinical
Trial Applications are in the process of being filed with
the relevant European agencies.
The trial is designed for rapid patient recruitment and
has a primary endpoint of overall survival. The duration
of the trial will be determined
by the number of deaths in the study group. Median survival
for this patient group is approximately 11 months. The
trial protocol includes the appointment
of a Safety and Efficacy Monitoring Board that will periodically
review the data and make recommendations based on the safety
and efficacy of
the different treatment arms. TRIST is expected to reach
a conclusion in 2008-09 and could support product registration
in 2009.
(ii) Colorectal cancer
Oxford BioMedica has advanced its discussions with the
QUASAR group, which is a UK-based clinical trial network, which has
been funded from a variety of sources including the UK Medical Research
Council and Department of Health. In November 2005, the Company reported
that QUASAR had expressed interest in conducting a Phase III trial of
TroVax in early stage (Stage II/III) colorectal cancer patients but that further evaluation was required. QUASAR has completed
its evaluation, confirmed its commitment and will seek funding for the
proposed trial through the appropriate agencies.
The proposed design is a randomised trial in about 3,000 patients. TroVax
would be used during or after adjuvant chemotherapy with a primary endpoint
of disease-free survival at three years. The study is likely to be configured
to enable product registration in Europe and the USA. The QUASAR group
has successfully conducted other large studies of adjuvant therapy in
this disease setting. These previous QUASAR trials have enrolled about
7,000 patients over the last seven years.
Separately, the Company is planning a randomised trial in first-line
treatment of metastatic (Stage IV) colorectal cancer. The preliminary
trial design is to evaluate TroVax alongside standard of care treatment.
It could be configured as a Phase IIb or Phase III trial. The final design
of this trial depends on the outcome of licensing discussions, since the
Company expects this trial to be funded and conducted by a commercial
partner.
(iii) Prostate cancer
Oxford BioMedica reported on 23 May 2006 that a Phase II
trial of TroVax in patients with prostate cancer had started. The trial,
which is supported by the Methodist Hospital in Houston, is designed
to enrol 24 men with hormone-refractory prostate cancer who have previously
received chemotherapy or have refused chemotherapy and have progressive
disease. The open-label trial has two arms (12 patients each) to assess
the activity of TroVax alone versus TroVax alongside an approved treatment
for prostate cancer, granulocyte macrophage-colony stimulating factor
(GM-CSF). The primary objectives of the trial are to evaluate the safety
and synergies of the combination treatment. Eleven patients have been
enrolled into the trial to date.
-
ends -
|
