OncoGenex provides update on Phase 3 ENSPIRIT trial evaluating custirsen for treatment of NSCLC

Apr 30 2015

Protocol Amended to Provide Faster Assessment of Survival Outcomes with Reduced Trial Size

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."

SOURCE OncoGenex Pharmaceuticals, Inc.