Date: 2016-10-25
Type of information: Results
phase: 2
Announcement: results
Company: OncoGenex Pharmaceuticals (USA - WA)
Product: apatorsen (OGX-427)
Action
mechanism: antisense oligonucleotide/heat shock protein inhibitor. Heat shock protein 27 (Hsp27) is an intracellular protein that protects cancer cells by helping them survive, leading to treatment resistance and more aggressive cancer phenotypes. Expression of Hsp27 is limited in normal cells but is elevated in many types of cancer cells making Hsp27 an attractive therapeutic target for cancer treatment. Apatorsen is a once-weekly intravenous (IV) experimental drug designed to inhibit production of Hsp27 to disable cancer cells’ defenses and overcome treatment resistance.
Disease: metastatic bladder cancer
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: The Borealis clinical trial is a randomized, open-label Phase 2 clinical trial to evaluate whether suppression of Hsp27 (Heat shock protein 27) production using OGX-427, a second-generation antisense oligonucleotide (ASO), in combination with docetaxel can prolong survival time compared to docetaxel alone in participants with locally advanced or metastatic urothelial carcinoma (UC) that are relapsed or refractory after receiving a platinum-containing regimen. This trial is the third one assessing the ability of apatorsen to improve outcomes for patients in this tumor type. (NCT01780545)
Latest
news: * On November 10, 2016, OncoGenex Pharmaceuticals announced its third quarter 2016 financial results. * On October 25, 2016, OncoGenex Pharmaceuticals announced positive survival results from the final analysis of the Phase 2 Borealis-2™ trial of apatorsen in combination with docetaxel treatment that enrolled 200 patients with metastatic bladder cancer whose disease had progressed following first-line platinum-based chemotherapy. Patients who received apatorsen treatment experienced a 20% reduction in risk of death, compared to patients receiving docetaxel alone (HR=.80; 95% CI: 0.65-0.98; p=0.078). The primary analysis was a superiority test of overall survival, performed at a one-sided 0.10 significance level using a stratified log-rank test. The trial was conducted by the Hoosier Cancer Research Network at 28 sites across the United States . Safety results in patients treated with apatorsen and docetaxel were similar to those observed in patients treated with docetaxel alone. Apatorsen is designed to inhibit production of heat shock protein 27 (Hsp27) to disable cancer cells' defenses and overcome treatment resistance. Hsp27 is an intracellular protein that protects cancer cells by helping them survive, leading to resistance and more aggressive cancer phenotypes. Oncogene is now looking forward to completing the full data analysis from Borealis-2 and considering these data in the exploration of strategic alternatives as announced in mid-August. * On December 9, 2015, OncoGenex Pharmaceuticals announced that the independent Data Safety Monitoring Board (DSMB) at Dana-Farber/Harvard Cancer Center has recommended that the Phase 2 Borealis-2™ trial continue as planned after completing the pre-specified futility analysis. Investigators have concluded in the bladder cancer trials conducted to date that 600mg apatorsen administered intravenously and all apatorsen doses administered intravesically have been well tolerated. In addition to Borealis-2, OncoGenex expects to announce progression-free survival results for the Phase 2 Spruce™ trial in the first quarter of 2016 with continued overall survival follow up. * On June 1, 2015, OncoGenex Pharmaceuticals announced that results from an exploratory analysis of the Phase 2 Borealis-1™ trial showed that metastatic bladder cancer patients with poor prognostic features benefited from apatorsen 600mg added to first-line chemotherapy compared to chemotherapy alone. Patients in the trial with a Karnofsky Performance Status (KPS) of 80 percent or less, a common indicator of poor prognosis, experienced a 50 percent reduction in risk of death with the addition of apatorsen therapy (OS HR = 0.50). These results were presented in an oral session at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago . Borealis-1 enrolled approximately 180 patients with documented metastatic or locally inoperable transitional cell carcinoma (TCC) of the urinary tract who had not previously received chemotherapy for metastatic disease and were not candidates for potentially curative surgery or radiotherapy. Patients were randomized to receive standard chemotherapy (gemcitabine/cisplatin) in combination with apatorsen at two dose levels (600mg and 1000mg) or gemcitabine/cisplatin plus placebo. The primary endpoint of the trial was overall survival. Secondary endpoints measured disease response as well as safety of each of the two doses of apatorsen.
The company also announced that it does not currently intend to fund further development of apatorsen in bladder cancer without a collaboration partner.
Exploratory analysis of study results showed that survival outcome was impacted by the following prognostic risk factors: KPS, liver involvement, low hemoglobin and high alkaline phosphatase. Patients who had these poor prognostic features benefited most from 600mg apatorsen therapy. Median overall survival in the poor prognostic group was 11.9 months with 600mg apatorsen + gemcitabine/cisplatin compared to 9 months with gemcitabine/cisplatin alone (OS HR = .77). Importantly, 33 percent of patients in the trial had a KPS less than or equal to 80 percent, which was found to be the single most important risk factor for poor prognosis. These lower KPS, high-risk patients experienced a 50 percent reduction in risk of death (OS HR = 0.50) when 600mg apatorsen was added to chemotherapy.
Overall treatment was well tolerated. Most common Grade ?3 adverse events (AEs) were neutropenia, anemia, thrombocytopenia and hypertension. Frequency of ?3 Grade toxicities were: 89 percent (GC), 93 percent (GC+A 600) and 95 percent (GC+A 1000). GC+A 1000 had a higher treatment discontinuation rate due to AEs.
