April 12, 2017 /CNW/ – Oncolytics Biotech Inc. (TSX:ONC) (OTCQX:ONCYF) reported 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) (Free AACR Whitepaper) 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. Schedule your 30 min Free 1stOncology Demo! Registration Path in Metastatic Breast Cancer
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
At AACR (Free AACR Whitepaper) 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.