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. 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.
“We are obviously disappointed that custirsen was unable to demonstrate a survival benefit in prostate cancer. We would like to thank the patients who participated in the AFFINITY trial and their caregivers, as well as the investigators and their teams for their commitment to improving cancer care for patients who are in desperate need of new treatment options,” Scott Cormack, president and CEO of OncoGenex said in a press release.
OncoGenex will submit the final results as a late-breaking abstract to the European Society for Medical Oncology Congress, to be held in October in Copenhagen.
The company also will work with the U.S. Food and Drug Administration (FDA) to assess options for an early analysis of the Phase 3 ENSPIRIT trial, set to evaluate custirsen combined with docetaxel as second-line therapy in 700 patients with non-small cell lung cancer whose disease progressed after initial chemotherapy treatment.
“Given that the ENSPIRIT trial has nearly completed enrollment and we believe there are likely a sufficient number of events to determine the effect of custirsen in NSCLC, we are eager to expedite the final data analysis, which would allow us to conserve resources and fully understand the value of the asset,” Cormack said.