The Phase 3 AFFINITY Trial failed to met its primary endpoint of significantly improved overall survival in men with metastatic castrate-resistant prostate cancer (CRPC) being treated with custirsen, the therapy’s maker, OncoGenex announced.
The international, randomized, open-label study evaluated 634 men with CRPC whose disease had progressed despite treatment with docetaxel (taxotere). In the trial, patients received weekly doses of cabazitaxel or prednisone with or without the addition of custirsen (OGX-011). Treatment continued until disease progression, unacceptable toxicity or completion of 10 cycles.
Results showed that adding custirsen did not provide significant overall survival benefit. Adverse events were consistent with those observed in previous trials of custirsen in men with CRPC.
Custirsen is designed to inhibit the production of clusterin, a protein involved 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 is overexpressed in a number of cancers, including prostate cancer.
Increased clusterin production is associated with faster rates of cancer progression, treatment resistance, and shorter survival duration. By inhibiting clusterin, custirsen aims to alter tumor dynamics, slowing tumor growth and resistance to other treatments to amplify the benefits of therapy, including survival.