–Company Intends to Proceed Into Follow-On Registration Study in This
Indication–
TORONTO, Nov. 21, 2013 /PRNewswire/ – Oncolytics Biotech Inc. (“Oncolytics” or
the “Company”) (TSX:ONC, NASDAQ:ONCY) today announced positive top-line
data for the endpoints in its double blinded, randomized clinical study
examining REOLYSIN in combination with carboplatin and paclitaxel in
patients with second-line platinum-refractory, taxane-naïve head and
neck cancers (REO 018).
Summary of Trial Results
Efficacy
-
An analysis was performed on an intent-to-treat basis of the 118
patients with loco-regional head and neck cancer, with or without
metastases. Patients in the control arm were treated with carboplatin
and paclitaxel, while patients in the test arm were treated with
carboplatin, paclitaxel and REOLYSIN; -
The analysis showed a median progression free survival (PFS) of 94 days
(13.4 weeks) in the test arm (n=62), versus 50 days (7.1 weeks) in the
control arm (n=56). The test arm maintained a PFS benefit over the
control arm through five cycles of therapy; -
Eighty-eight loco-regional patients did not receive additional therapy
following discontinuation of study treatment. An analysis of these
patients showed a median overall survival (OS) of 150 days (21.4 weeks)
in the test arm (n=50), versus 115 days (16.4 weeks) in the control arm
(n=38), and; -
As of the time of reporting, there have not been a sufficient number of
events (i.e. patient deaths) to conduct a survival analysis of patients in the
metastatic-only group (i.e. those patients with no loco-regional
recurrence).
Safety
- REOLYSIN was safe and well-tolerated by patients;
-
The side effects experienced by patients in the test arm of the study
were consistent with expectations based on outcomes of earlier clinical
studies using REOLYSIN. Patients on the test arm of the study
experienced a higher incidence of flu-like symptoms consistent with
treatment with a virus, most commonly mild fever, chills, nausea and
diarrhea, on both a per-patient and a per-cycle basis; and -
Fewer patients required dose reductions of paclitaxel due to neuropathy
or neurotoxicity on the test arm than the control arm (zero in the test
arm versus six in the control arm; p=0.028). On this basis, the Company
intends to explore the potential chemoprotective and neuroprotective
properties of REOLYSIN in future clinical studies.
“The overall goal of this clinical trial was to determine the specific
parameters for the use of REOLYSIN in a registration study in head and
neck cancers,” said Dr. Brad Thompson, President and CEO of Oncolytics.
“We are excited to move forward with our head and neck program, and
intend to discuss the design and execution of a follow-on registration
study with regulators in the near future.”
Implications of the Results
As disclosed in the press release dated September 12, 2012, Oncolytics
intends to treat this expanded first stage of the REO 018 clinical
trial as a separate supportive study to a planned registration study
that will be similar to, and take the place of, the original second
stage of the REO 018 clinical trial. Based on these data, the Company
intends to discuss the design and execution of a randomized, follow-on
Phase III registration study in patients with loco-regional head and
neck cancer with regulators in multiple jurisdictions.
Detailed Efficacy Data
The REO 018 study enrolled 167 patients. The efficacy analysis was
performed on an intent-to-treat basis of the 118 patients with
loco-regional head and neck cancer with or without metastatic disease.
In the intent-to-treat patient population, PFS, progression at first
post-treatment scan, cycles of therapy received, and tumour shrinkage
at first post-treatment scan were analyzed.
The analysis showed a median PFS of 94 days (13.4 weeks) in the test arm
(n=62), versus 50 days (7.1 weeks) in the control arm (n=56). The test
arm maintained a PFS benefit over the control arm through five cycles
of therapy.
A number of patients on study received additional treatments with other
agents following discontinuation of study treatment in accordance with
the clinical practices of individual enrolling centres. Thirty of the
118 patients in the loco-regional group received at least one therapy
with other agents after study therapy was discontinued. A greater
number of patients in the control arm received post-discontinuation
therapy versus the test arm. This imbalance created a “confounding,” or
distorting, effect on OS (Pazdur; The Oncologist 2008, 13:19-21), as such additional therapy can extend the patients’
lifespan beyond that expected from receiving the study therapy.
Eighty-eight loco-regional patients did not receive additional therapy
and an analysis of these patients showed a median OS of 150 days (21.4
weeks) in the test arm (n=50) versus 115 days (16.4 weeks) in the
control arm (n=38).
Patients were evaluated for progression at the first scheduled
post-treatment scan (performed at six weeks, post-cycle two of
therapy). Of 62 patients on the test arm, 32.3% had progressed,
compared with 51.8% of the 56 patients on the control arm (p=0.04). The
patients were also evaluated for the total cycles of therapy received.
The patients on the test arm had received a median of four cycles of
therapy, versus a median of two cycles on the control arm. The same
proportion of patients from each arm remained on study at five cycles.
Of 86 patients with measurable disease at the first post-treatment scan,
the test arm (n=48) had a statistically significant increase in tumour
shrinkage over the control arm (n= 38; p=0.049).
As of the time of reporting, there have not been a sufficient number of
events (i.e. patient deaths) to conduct a survival analysis of patients
in the metastatic-only group.
Detailed Safety Data
Overall, the treatment combination was found to be safe and well
tolerated by patients. The adverse events (AEs) experienced by patients
in the test arm of this, the first double blinded, randomized clinical
study of REOLYSIN, were consistent with expectations based on the
outcomes of earlier single arm clinical studies of REOLYSIN, both as a
monotherapy and in combination with chemotherapeutic agents.
Investigators reported a statistically significant increase in the
number of patients on the test arm experiencing mild fever, chills,
nausea, and diarrhea. These adverse events were generally mild, with
three patients on the test arm experiencing Grade 3 diarrhea; one
patient on the control arm and two on the test arm experiencing Grade 3
nausea; and no reports, on either arm, of Grade 3 fever or chills (in
the absence of infection). There was an increase in the percentage of
patients at each cycle with fever in the test arm (mean=27.2%,
median=25.9%), versus the control arm (mean=5.3%, median=4.8%). There
was also an increase in the percentage of patients at each cycle of
therapy exhibiting flu-like symptoms in the test arm (mean=87.9%,
median=81.7%) versus the control arm (mean=47.3%, median=45%).
Hematological data showed no statistical or clinical differences in
hemoglobin, lymphocytes, or platelet counts. Twenty patients with
decreased white blood cell counts (WBC) (Grade 3 and 4) were noted in
the test arm versus 10 in the control arm (p=0.068). There were 21
patients in the test arm with decreased absolute neutrophil counts
(ANC) (Grade 3 and 4) versus 15 in the control arm. There were nine
patients on each arm who had Serious Adverse Events (SAE’s) with
hospitalization that were related to a low ANC, with or without
demonstrated infection.
There were no clinical or statistical differences in terms of hepatic or
renal evaluations.
There were 19 SAEs not related to flu-like illness that were judged by
the investigators to be at least possibly related to treatment in the
control arm and 24 in the test arm. There was no pattern in the nature
of SAEs observed between arms, except for flu-like signs and symptoms.
Fewer patients on the test arm required dose reductions of paclitaxel
due to neuropathy or neurotoxicity than the control arm. There were no
dose reductions for neuropathy in the test arm versus six in the
control arm (p=0.028). On the basis of these data, the Company intends
to further investigate the possibility that REOLYSIN may have a
neuroprotective and/or chemoprotective effect.
“These data demonstrate that REOLYSIN can be safely added to this
chemotherapeutic combination,” said George M. Gill, MD, Senior Vice
President, Regulatory Affairs, and Chief Safety Officer of Oncolytics.
“This controlled comparison supports our belief that the addition of
REOLYSIN to other regimens will not increase the frequency or severity
of adverse events caused by the chemotherapeutic agents with which it
is combined.”
REO 018 Study Design and Analytical Considerations
REO 018 is a randomized, double blinded, two arm, multi-centre trial
assessing the intravenous administration of REOLYSIN with the
chemotherapy combination of paclitaxel and carboplatin versus the
chemotherapy alone in patients with recurrent and/or metastatic
squamous cell carcinoma of the head and neck who have progressed on or
after prior platinum-based chemotherapy. The trial is examining 167
patients segregated into two patient groups: patients with local
recurrent disease, with or without distal metastases, and those with
only distal metastases. The Company is treating REO 018 as a separate
supportive study to an intended subsequent registration study.
All patients received treatment every three weeks (21-day cycles) with
paclitaxel and carboplatin and also received, on a blinded basis,
either intravenous placebo or intravenous REOLYSIN. All dosing took
place in the first five days of each cycle with all patients receiving
standard intravenous doses of paclitaxel and carboplatin on day one
only, and either intravenous placebo or intravenous REOLYSIN at a dose
of 3×1010 TCID50 on days one to five. Patients could continue to receive the trial
combination therapy for up to eight cycles and, thereafter, blinded
placebo or blinded REOLYSIN until the patient had progressive disease
or met other criteria for discontinuation from the trial.
On December 13, 2012, the Company announced positive data on an endpoint
examining initial percentage tumour changes between the pre-treatment
and first post-treatment scans (typically performed at six weeks
post-first treatment) of all patients enrolled in the study. The
analysis was designed to assess early differences in response between
loco-regional tumours and metastatic tumours, as classified and
observed by the investigators.
Conference Call Details
Dr. Brad Thompson, President and CEO of Oncolytics, will host a
conference call and webcast on Thursday, November 21, 2013 at 6:00 a.m.
MT (8:00 a.m. ET) to discuss in more depth the data from the Company’s
REO 018 trial in head and neck cancers. To access the conference call
by telephone, dial 1-647-427-7450 or 1-888-231-8191. A live audio
webcast will also be available at the following link: http://www.newswire.ca/en/webcast/detail/1265023/1394835 or through the Company’s website at www.oncolyticsbiotech.com/presentations. Please connect at least 10 minutes prior to the webcast to ensure
adequate time for any software to download. A replay of the webcast
will be available at www.oncolyticsbiotech.com/presentations and will also be available by telephone through November 28, 2013. To
access the telephone replay, dial 1-416-849-0833 or 1-855-859-2056 and
enter reservation number 15177323 followed by the number sign. The Company also intends to post the prepared remarks from the call to
its corporate website following the call.
About Oncolytics Biotech Inc.
Oncolytics is a Calgary-based biotechnology company focused on the
development of oncolytic viruses as potential cancer therapeutics.
Oncolytics’ clinical program includes a variety of human trials
including a Phase III trial in head and neck cancers, and six
randomized Phase II studies in prostate, colorectal, breast, lung,
pancreatic and ovarian cancer using REOLYSIN®, its proprietary formulation of the human reovirus. For further
information about Oncolytics, please visit: www.oncolyticsbiotech.com.
This press release contains forward-looking statements within the
meaning of the U.S. Securities Act of 1933, as amended, and U.S.
Securities Exchange Act of 1934, as amended, and forward-looking
information within the meaning of Canadian securities laws. Statements,
other than statements of historical facts, included in this press
release that address activities, events or developments that Oncolytics
expects or anticipates will or may occur in the future, including such
things as, the Company’s expectations related to the REO 018 head and
neck cancers trial of REOLYSIN in combination with carboplatin and
paclitaxel, and the Company’s belief as to the potential of REOLYSIN as
a cancer therapeutic, and other such matters are forward-looking statements and
forward-looking information and involve known and unknown risks and
uncertainties, which could cause the Company’s actual results to differ
materially from those in the forward-looking statements and
forward-looking information. Such risks and uncertainties include,
among others, risks related to the statistical sufficiency of patient
enrollment numbers in separate patient groups, the availability of
funds and resources to pursue research and development projects, the
efficacy of REOLYSIN as a cancer treatment, the tolerability of
REOLYSIN outside a controlled test, the success and timely completion
of clinical studies and trials, the Company’s ability to successfully
commercialize REOLYSIN, uncertainties related to the research and
development of pharmaceuticals and uncertainties related to the
regulatory process. Investors should consult the Company’s quarterly
and annual filings with the Canadian and U.S. securities commissions
for additional information on risks and uncertainties relating to the
forward-looking statement and forward-looking information. Investors
are cautioned against placing undue reliance on forward-looking
statements and forward-looking information. The Company does not
undertake to update these forward-looking statements and
forward-looking information, except as required by applicable laws.
SOURCE Oncolytics Biotech Inc.
Released November 21, 2013