OncoGenex Pharmaceuticals, Inc. has announced results from the Phase 3 SYNERGY trial. Top-line survival results indicate that the addition of custirsen to standard first-line docetaxel/prednisone therapy did not meet the primary endpoint of a statistically significant improvement in overall survival in men with metastatic castrate-resistant prostate cancer (CRPC), compared to docetaxel/prednisone alone (median survival 23.4 months vs 22.2 months, respectively; hazard ratio 0.93 and one-sided p value 0.207). The adverse events observed were similar to custirsen's known adverse event profile.
"The results of SYNERGY are unexpected, particularly given the wealth of scientific evidence supporting the targeting of clusterin to combat treatment resistance in first-line prostate cancer," said Scott Cormack, President and CEO of OncoGenex. "A thorough analysis of the data is underway to understand the potential factors that may have contributed to the results. Importantly, we remain strong in our belief that targeting mechanisms of treatment resistance is a critical path forward in the fight against cancer and we continue to actively pursue this approach through the two ongoing Phase 3 trials of custirsen and the seven Phase 2 trials of apatorsen in four tumor types. We would like to thank the men who participated in the SYNERGY trial and the friends and families who supported them."
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.
As part of Phase 1 and Phase 2 clinical trials, custirsen was administered to 294 patients with various types of cancer. The majority of adverse events were mild. The most common adverse events associated with custirsen consisted of flu-like symptoms. The most common serious adverse events (SAE) associated with custirsen were febrile neutropenia, fever, pleural effusion, and dyspnea. Each SAE event was observed in approximately 2%-4% of patients.
The SYNERGY trial enrolled 1,022 men with mCRPC at more than 130 cancer centers throughout North America, Europe, Israel and South Korea. In the investigational arm of the trial, custirsen was administered as a weekly infusion of 640 mg following three loading doses, in combination with docetaxel and prednisone given as standard 3-week cycles. Patients in the active comparator arm received docetaxel and prednisone without custirsen. In both arms, patients were treated until disease progression, unacceptable toxicity, or completion of up to 10 cycles, unless additional cycles were deemed beneficial. Full efficacy and safety data from SYNERGY will be submitted for presentation at an upcoming scientific conference.