Protocol Amended to Provide Faster Assessment of Survival Outcomes with Reduced Trial Size
BOTHELL, Wash. and VANCOUVER, British Columbia, April 30, 2015 /PRNewswire/ -- OncoGenex Pharmaceuticals, Inc. (NASDAQ: OGXI) announced today it has filed an amendment with the U.S. Food and Drug Administration, as well as initiated filing with regulatory agencies in other countries, to amend the statistical design and analysis plan of its pivotal, international Phase 3 ENSPIRIT trial evaluating custirsen in the treatment of non-small cell lung cancer (NSCLC). OncoGenex recently regained the rights to the investigational compound from Teva Pharmaceuticals Ltd. and is currently in the process of assuming sponsorship for all clinical development related to custirsen.
The protocol amendment is designed to reduce the number of required patients enrolled in the trial and include an earlier, more rigorous second interim futility analysis. The protocol will now also include additional analyses, specifically an evaluation of overall survival (OS) by patient histology, as well as the effect of custirsen's efficacy among patients with poor prognostic risk factors. These changes do not affect the criteria for enrollment or conduct of the study, which continues to accrue patients. Enrollment is expected to be completed in the second half of 2016.
"The majority of people with NSCLC do not have specific genetic mutations that will respond to targeted therapy. New treatment options like custirsen, added to standard of care chemotherapy, are urgently needed for patients to control their cancer once it has progressed," said Cindy Jacobs, PhD, MD, Chief Medical Officer and Executive Vice President of OncoGenex. "We believe these rigorous protocol changes reflect the most responsible course of action for these patients, who unfortunately do not have the gift of time. These changes will provide the critical information we need to more quickly understand custirsen's activity and guide future development plans."
Under the revised protocol, the following changes include:
- A reduced sample size: Changes to trial sample size were based on revising the hypothesized hazard ratio to 0.75 instead of 0.80, resulting in a sample size of 700 patients instead of 1,100. This change maintains a power of 90% while assessing for a more clinically meaningful difference.
- Revised timing of second survival futility analysis: The second analysis will now take place when 40% of events occur, instead of the original 50%. As previously reported, OncoGenex expects this to occur in mid-2015. An Independent Data Monitoring Committee recommended the ENSPIRIT trial continue based on the outcome of the first interim futility analysis in August 2014. Trial results will remain blinded to the Independent Data Monitoring Committee and OncoGenex, as the sponsor, unless futility is observed.
- Additional analyses: An evaluation of OS by patient histology, and the effect of custirsen's efficacy among patients with varying risk factors and disease parameters, will now be conducted.
"These protocol changes will provide us with a more expedient path to assess custirsen's potential survival benefit," said Scott Cormack, President and CEO of OncoGenex. "Reducing the sample size of the trial will enable us to evaluate the potential of custirsen in an earlier timeframe, hopefully accelerating the path to regulatory review and potential availability. We believe these are important steps in our efforts to give patients with advanced NSCLC more choices when their initial treatments fail."
Conference Call Details
OncoGenex will host a conference call at 4:30 p.m. Eastern Time today, Thursday, April 30, 2015, to provide an overview of today's announcement. A live event will be available on the Investor Relations section of the OncoGenex website at www.OncoGenex.com. Alternatively, you may access the live conference call by dialing (877) 606-1416 (U.S. & Canada) or (707) 287-9313 (International). A webcast replay will be available approximately two hours after the call and will be archived on www.OncoGenex.com for 90 days.
About the Phase 3 ENSPIRIT Trial
The Phase 3 ENSPIRIT trial is an international, randomized, open-label trial designed to evaluate custirsen for the treatment of advanced or metastatic non-small cell lung cancer (NSCLC) in 700 patients who have progressed after initial chemotherapy treatment. The trial will investigate if combining custirsen with docetaxel, a standard second-line NSCLC chemotherapy, has the potential to improve survival outcomes compared to docetaxel alone in these patients. The trial is expected to enroll patients at approximately 50 sites globally. For more information on the ENSPIRIT trial, please visit http://clinicaltrials.gov/ct2/show/NCT01630733.
Custirsen is also being evaluated in the ongoing Phase 3 AFFINITY trial with second-line chemotherapy in men with metastatic castrate-resistant prostate cancer. After regaining development control of custirsen, and based on the improved survival benefit observed in poor prognostic patients treated with custirsen in the completed Phase 3 SYNERGY trial, OncoGenex plans to seek regulatory guidance regarding amendments to the AFFINITY protocol.
Custirsen is an experimental drug that is designed to block the production of the protein clusterin, which may play a fundamental role in cancer cell survival and treatment resistance. Clusterin is upregulated in tumor cells in response to treatment interventions such as chemotherapy, hormone ablation and radiation therapy and has been found to be overexpressed in a number of cancers, including prostate, lung, breast and bladder. Increased clusterin production has been linked to faster rates of cancer progression, treatment resistance and shorter survival duration. By inhibiting clusterin, custirsen is designed to alter tumor dynamics, slowing tumor growth and resistance to partner treatments, so that the benefits of therapy, including survival, may be extended.
Custirsen has Fast Track designation by the U.S. Food and Drug Administration for NSCLC and metastatic castrate-resistant prostate cancer.
OncoGenex is a biopharmaceutical company committed to the development and commercialization of new therapies that address treatment resistance in cancer patients. OncoGenex has a diverse oncology pipeline, with each product candidate having a distinct mechanism of action and representing a unique opportunity for cancer drug development. Custirsen is currently in Phase 3 clinical development as a treatment in men with metastatic castrate-resistant prostate cancer and in patients with advanced, unresectable non-small cell lung cancer. Apatorsen is in Phase 2 clinical development and OGX-225 is currently in pre-clinical development. More information is available at www.OncoGenex.com and at the company's Twitter account: https://twitter.com/OncoGenex_IR.
OncoGenex' Forward Looking Statements
This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements concerning the expected transfer from Teva to OncoGenex of clinical activities related to custirsen, statements regarding expected clinical trial accrual, completion and design and statements regarding the potential benefits and potential development of our product candidates. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. These statements are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and assumptions that could cause actual results to differ materially from those described in the forward-looking statements. Such forward-looking statements are subject to risks and uncertainties, including, among others, the risk that transfer of clinical trial responsibilities from Teva to OncoGenex is not completed as and when anticipated, the risk of delays in our expected clinical trials and the risk that changes in our clinical trial design are not acceptable to regulatory authorities or do not yield the expected benefits, the risk that new developments in the rapidly evolving cancer therapy landscape require changes in our clinical trial plans or limit the potential benefits of our product, the risk that our product candidates do not demonstrate the hypothesized or expected benefits and the other factors described in our risk factors set forth in our filings with the Securities and Exchange Commission from time to time, including the Company's Annual Report on Form 10-K and Quarterly Reports on Form 10-Q. The Company undertakes no obligation to update the forward-looking statements contained herein or to reflect events or circumstances occurring after the date hereof, other than as may be required by applicable law.
SOURCE OncoGenex Pharmaceuticals, Inc.