Top-line results from a phase III trial evaluating the addition of custirsen to standard first-line docetaxel/prednisone therapy did not meet its primary endpoint of a statistically significant improvement in overall survival in men with metastatic castrate-resistant prostate cancer when compared to docetaxel/prednisone alone.
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.
In the trial, named SYNERGY, median survival was 23.4 months in the custirsen arm compared to 22.2 months in the control arm (HR=0.93; one-sided p value 0.207). The adverse events observed were similar to the 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 Pharmaceuticals Inc., the drug’s sponsor.
“A thorough analysis of the data is underway to understand the potential factors that may have contributed to the results.” The company will continue to pursue two ongoing phase III trials of custirsen and the seven phase II trials of apatorsen in four tumor types, he said.
