--Initial Registration Pathway to Focus on
Chemotherapy Combinations
in Patients with Metastatic Breast Cancer--
CALGARY, April 12, 2017 /PRNewswire/ - Oncolytics
Biotech® Inc. (TSX:ONC) (OTCQX:ONCYF) today announced
its initial registration pathway and clinical development plan for
REOLYSIN®, its proprietary immuno-oncology viral
agent. The Company's clinical development plan has two main
objectives. The primary objective is to obtain regulatory
approval for REOLYSIN as quickly as possible and is based on the
compelling metastatic breast cancer survival data recently
presented at the American Academy of Cancer Research (AACR) Annual
Meeting, in Washington, D.C.
The second objective is to expand REOLYSIN into commercially
valuable new treatment areas that include immunotherapy and
immunomodulatory (IMiD) agents in collaboration with pharmaceutical
partners.
Registration Path in Metastatic Breast Cancer
At AACR
the Canadian Cancer Trials Group (CCTG) presented positive overall
survival (OS) data from an open-label, randomized, phase 2 study
assessing the therapeutic combination of intravenously-administered
REOLYSIN given in combination with the chemotherapy agent
paclitaxel versus paclitaxel alone, in patients with advanced or
metastatic breast cancer (IND 213). Based on CCTG's compelling
clinical results in this indication, where the combined treatment
demonstrated a statistically significantly increase in median OS,
the Company has consulted with key opinion leaders to develop a
registration strategy. Management believes that these results
are the most compelling data generated by the Company to date and
will support a rapid route to market in an important therapeutic
area.
The 74-patient study, powered to 90% and designed by the CCTG,
reported that in the intention-to-treat patient population there
was a statistically significant improvement in median OS from 10.4
months on the control arm to 17.4 months on the test arm (Hazard
Ratio 0.65, 80% CI 0.46-0.91, p=0.1). The presentation also
indicated that of the 74 patients in the study, 82 percent (61
patients) presented with mutated p53 tumors. The results showed
that patients with mutant p53 metastatic breast cancer who were
treated with REOLYSIN in combination with paclitaxel (n=30)
had a median OS of 20.9 months versus 10.4 months in patients
treated only with paclitaxel (n=31) (Hazard Ratio 0.52, 80% CI
0.35-0.76, p = 0.03).
The Company intends to present this data to regulators as part
of an End-of-Phase 2 Meeting with a focus on obtaining scientific
advice to support a registration pathway. Specific features of any
future clinical studies are expected to include: overall survival
as a primary endpoint; other exploratory endpoints to identify
potential markers of response; and a trial design to ensure a
sufficient number of patients are run to reach a statistically
significant outcome while balancing the financial resources
required.
"We have developed a comprehensive clinical plan for REOLYSIN
predicated on its mechanism of action, excellent safety profile
with more than one thousand patients treated and the compelling
overall survival data recently announced in metastatic breast
cancer," said Dr. Matt Coffey,
President and CEO of Oncolytics. "The registration path in the near
term will look at combinations of REOLYSIN and chemotherapy agents,
beginning with metastatic breast cancer. In parallel, we
intend to look at other pillars of the platform and our long-range
focus for REOLYSIN includes establishing collaborations with large
pharma to study both immunotherapy and immunomodulatory drug
combinations, such as the recently announced collaboration with
Myeloma UK and Celgene using Revlimid® and
Imnovid® in combination with REOLYSIN in myeloma
patients."
Mechanism of Action
REOLYSIN is a first-in-class,
systemically administered, immuno-oncology viral agent with a
robust safety history. During the last few years, in both
single-arm and randomized phase 2 clinical studies, REOLYSIN, in
combination with various chemotherapeutic agents, has shown a trend
to improve OS in certain indications and patient populations, while
having a limited impact on objective response rate (ORR) or
progression-free survival (PFS). This therapeutic profile is
consistent with those observed with approved immunotherapies, where
patients receive OS benefit, the gold standard of registrational
endpoints, without seeing meaningful improvements in ORR or
PFS.
REOLYSIN has multiple components to its mechanism of action
(MOA):
- Direct tumor lysis – selective viral replication in
permissive cancer cells leading to tumor cell lysis;
- Innate immune response – viral replication resulting in
a cascade of chemokines/cytokines causing NK (natural killer) cells
to recognize and attack cancer cells; and
- Adaptive immune response – antigen presenting cells
(APCs) display tumor-associated antigens (TAA) and viral-associated
antigens (VAA) to educate T-cells to recognize and destroy cancer
cells.
Clinical Development Plan
Based on Oncolytics'
evolving understanding of REOLYSIN's mechanism of action, along
with survival data generated to date, the Company is dedicated to
the metastatic breast cancer program as its primary focus to
quickly move the agent towards a commercial path. In parallel,
management has identified two additional pathways that will be
advanced simultaneously in collaboration with large pharma
colleagues to support the second objective of expanding REOLYSIN
into commercially valuable new treatment areas:
Combinations with IMiDs
The initial activity
supporting the innate immunity component of REOLYSIN's MOA, is in
collaboration with cancer charity Myeloma UK and Celgene. MUK
eleven was launched in March of this year: a first of its
kind immunotherapy trial that aims to modulate the immune system to
target myeloma. The Phase 1b trial will study REOLYSIN in
combination with Celgene's Imnovid® (pomalidomide) or
Revlimid® (lenalidomide) as a rescue treatment in
relapsing myeloma patients. The dose escalation trial will look at
the safety and tolerability of these combinations, and will
investigate whether the addition of REOLYSIN extends disease
control in this patient group.
The trial will recruit approximately 44 patients across up to
six Myeloma UK Clinical Trial Network centres in the UK. MUK
eleven is part of the Myeloma UK Clinical Trial Network, a
portfolio of early-stage trials coordinated by the Clinical Trials
Research Unit at the University of Leeds, which aims to test and
speed up access to promising new treatments for patients.
Oncolytics and Celgene UK & Ireland are providing their respective
products for MUK eleven: Oncolytics is providing REOLYSIN
and Celgene UK & Ireland is
providing Imnovid® and Revlimid®.
Combinations with Immunotherapy
In support of
the adaptive immunity component of the MOA, the Company is
currently running its first study in combination with an emerging
class of immuno-oncology agents known as checkpoint inhibitors. REO
024 is an open-label phase 1b trial to determine the safety and
dose-limiting toxicity of REOLYSIN in combination with
pembrolizumab (KEYTRUDA®) and chemotherapy in patients
with histologically confirmed, advanced or metastatic pancreatic
adenocarcinoma who have failed, or did not tolerate, first-line
treatment. The goal of this study is to establish the safety
profile of the REOLYSIN/KEYTRUDA combination and to determine how a
checkpoint inhibitor could improve the immune system's ability to
recognize cancer cells through the stimulation of the adaptive
immune response in patients caused by REOLYSIN. The Company expects
to report on the safety data from REO 024 in 2017 and looks to
expand its clinical collaborations using other checkpoint inhibitor
agents and investigating different indications, dose levels and
efficacy.
"While our near-term focus will be on chemotherapy combinations,
our longer-term goal is to establish REOLYSIN as the backbone of an
immuno-oncology regimen in combination with other agents, including
checkpoint inhibitors and other immunomodulatory drugs," said Dr.
Andres Gutierrez, Chief Medical
Officer of Oncolytics. "The combinations with emerging
immunotherapies could be transformative when taking into account
REOLYSIN's continuing positive safety profile in ongoing
studies."
In summary, in 2017 Oncolytics expects to make progress against
a number of milestones including:
- Discussions with regulators focused on obtaining scientific
advice on the best registration path in metastatic breast
cancer;
- Announcing a detailed registration study in metastatic breast
cancer;
- Reporting safety data from the phase 1b REO 024 pancreatic
cancer study evaluating REOLYSIN in combination with pembrolizumab
(KEYTRUDA®); and
- Expanding clinical collaborations with large pharma in an
effort to support further development around the innate and
adaptive immunity components of REOLYSIN's MOA.
About Oncolytics Biotech Inc.
Oncolytics is a
biotechnology company developing REOLYSIN, an immuno-oncology
viral-agent, as a potential treatment for a variety of tumor types.
The compound induces selective tumor lysis and promotes an inflamed
tumor phenotype through innate and adaptive immune responses to
treat a variety of cancers. Oncolytics' clinical development
program emphasizes three pillars: chemotherapy combinations to
trigger selective tumor lysis; immuno-therapy combinations to
produce adaptive immune responses; and immune modulator (IMiD)
combinations to facilitate innate immune responses.
Oncolytics is currently planning its first registration study in
breast cancer, as well as studies in combination with checkpoint
inhibitors and IMID/targeted therapies in solid and hematological
malignancies. For further information about Oncolytics,
please visit: www.oncolyticsbiotech.com.
This press release contains forward-looking statements,
within the meaning of Section 27A of the Securities Act of
1933, as amended, and Section 21E of the Securities Exchange Act of
1934, as amended. Forward-looking statements, including the
Company's expectations related to the Phase 2 clinical trial in
breast cancer, future trials in this indication, the potential for
additional data from other studies, the potential for
collaborations, and the Company's belief as to the potential of
REOLYSIN as a cancer therapeutic, 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.
Such risks and uncertainties include, among others, 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, development and
manufacturing of pharmaceuticals, changes in technology, general
changes to the economic environment 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 statements. Investors should
consider statements that include the words "believes", "expects",
"anticipates", "intends", "estimates", "plans", "projects",
"should", or other expressions that are predictions of or indicate
future events or trends, to be uncertain and forward-looking.
Investors are cautioned against placing undue reliance on
forward-looking statements. The Company does not undertake to
update these forward-looking statements, except as required by
applicable laws.
SOURCE Oncolytics Biotech Inc.