Date: 2015-09-28
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the 2015 European Cancer Congress (ECC 2015) in Vienna
Company: OncoGenex Pharmaceuticals (USA - WA)
Product: custirsen
Action
mechanism: antisense oligonucleotide. Custirsen has been designed to inhibit the production of clusterin, a protein commonly over-produced in cancer cells, and one cause of treatment resistance. In Phase 2 trials of patients with metastatic CRPC, custirsen combined with docetaxel showed a 6.9 month improvement in overall survival over docetaxel alone. Additionally, 50 percent of patients experienced durable pain palliation for a duration of 12 weeks or longer. Custirsen has received Fast Track designation from the FDA.
Disease: metastatic castrate-resistant prostate cancer
Therapeutic area: Cancer - Oncology
Country:
Trial
details: The new trial aims to enroll approximately 630 men. It will be conducted in lieu of the Prostate Cancer Saturn Study, a trial designed with a primary endpoint of measuring a durable pain palliation benefit for custirsen in second-line treatment of CRPC.
Latest
news: * On September 28, 2015, OncoGenex Pharmaceuticals announced results from additional exploratory analyses of the Phase 3 SYNERGY trial demonstrating that custirsen treatment significantly lowered serum clusterin (sCLU) levels from baseline in men with metastatic castrate-resistant prostate cancer (mCRPC). In addition, these data presented showed that sCLU reductions after custirsen treatment resulted in higher two-year survival rates in patients who were at increased risk for poor outcomes. Of those patients with lower sCLU levels, the data also showed a correlation to an overall survival benefit for custirsen-treated patients who were at increased risk for poor outcomes. * On April 28, 2014, Teva and OncoGenex have announced results from the Phase III SYNERGY trial, a randomized, open-label, two-arm study comparing the combination of custirsen and standard first-line docetaxel/prednisone therapy to docetaxel/prednisone alone in men with metastatic castrate-resistant prostate cancer (CRPC). Top-line survival results indicate 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 (OS) in men with metastatic 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 (AEs) observed for custirsen were similar to its known AE profile. Full efficacy and safety data from SYNERGY will be submitted for presentation at an upcoming scientific conference. * On March 8, 2012, Teva Pharmaceutical and OncoGenex Pharmaceuticals have announced an update on their development program for custirsen, a product candidate being evaluated in Phase 3 studies for castrate-resistant prostate cancer (CRPC). In a revised agreement between the two companies, the clinical trial program will now include the initiation of a Phase 3 study to evaluate if custirsen has the potential to improve survival rates for prostate cancer patients when combined with the recently-approved, second-line chemotherapy drug Jevtana® (cabazitaxel). The new trial, which aims to enroll approximately 630 men and is expected to begin later this year, will be conducted in lieu of the Prostate Cancer Saturn Study, a trial designed with a primary endpoint of measuring a durable pain palliation benefit for custirsen in second-line treatment of CRPC. The shift in focus to evaluate overall survival in second-line prostate cancer is a result of numerous, recently-approved agents that are redefining the standard of care in this patient setting. Custirsen's other Phase 3 study, SYNERGY, evaluating a survival benefit in the first-line CRPC setting, continues to accrue patients and is expected to complete enrollment later this year. The companies are increasing the enrollment from 800 to 1000 patients to optimize the potential to be submitted to regulatory agencies independent of additional Phase 3 studies. The increase in enrollment is not expected to alter timelines for completion of the study.
A previous retrospective analysis from the SYNERGY trial showed a benefit with custirsen therapy in men with metastatic CRPC who had at least two of five common risk factors for poor prognosis. For those men, a 27 percent lower risk of death occurred when custirsen was used in combination with first-line docetaxel compared to docetaxel alone.
(Abstract: 2560 - Baseline serum clusterin level in patients with poor prognostic features was associated with response to custirsen treatment: Results from the phase 3 SYNERGY trial of docetaxel +/- custirsen, Monday, September 28, 2015 , 16:45 - 18:45 CEST , Hall C) The analysis presented at ECC 2015 further demonstrates the impact of custirsen treatment on mCRPC patients at increased risk for poor outcomes, including a reduced risk of death among poor prognostic patients who achieved lower sCLU levels (Day 140 Area Under Curve (AUC)) during treatment. Patients in the poor prognostic subgroup who were treated with custirsen and had reduced Day 140 AUC sCLU levels showed a trend for higher two-year survival status. A landmark analysis also showed that overall survival benefit for the custirsen arm appeared greater in the poor prognostic patients who achieved lower Day 140 AUC sCLU levels.
In patients with lower sCLU at baseline, a trend for greater effect of custirsen treatment on survival was also observed, especially in patients at increased risk for poor outcomes. Patients at risk for poor outcomes with low baseline sCLU treated with custirsen (n=176) experienced a median survival of 18.4 months, compared to 14.4 months for patients on the control arm (n=170) [HR=0.689 (95% CI: 0.483-0.983); the median baseline sCLU was 55.30 ug/mL for patients at risk for poor outcomes. In the subpopulation of patients with a good prognosis, patients with low baseline sCLU treated with custirsen (n=171) experienced a median survival of 31.2 months in comparison to 27.2 months for patients on the control arm (n=186) [HR = 0.823 (95% CI: 0.505-1.34); the median baseline sCLU was 53.2 ug/mL for patients with a good prognosis.
