Borealis-2: A randomized phase II study of OGX-427 (apatorsen) plus docetaxel versus docetaxel alone in platinum-resistant metastatic urothelial cancer (mUC) …

TK Choueiri, NM Hahn, L Werner, MM Regan… - 2017 - ascopubs.org
TK Choueiri, NM Hahn, L Werner, MM Regan, JE Rosenberg, BOREALIS-02 investigators
2017ascopubs.org
289 Background: OGX-427 (apatorsen; A) is an antisense oligonucleotide that binds Heat
shock protein 27 (Hsp27) mRNA with synergistic effect with chemotherapy. Borealis-2 is a
randomized multicenter phase 2 study of A in combination with docetaxel (D) vs. D alone in
advanced UC patients (pts) after at least 1 prior platinum-based therapy. Methods: The
primary objective was to determine whether D+ A prolonged overall survival (OS) vs D.
Patients were stratified (time from prior systemic chemotherapy; Bellmunt criteria) and …
289
Background: OGX-427 (apatorsen; A) is an antisense oligonucleotide that binds Heat shock protein 27 (Hsp27) mRNA with synergistic effect with chemotherapy. Borealis-2 is a randomized multicenter phase 2 study of A in combination with docetaxel (D) vs. D alone in advanced UC patients (pts) after at least 1 prior platinum-based therapy. Methods: The primary objective was to determine whether D+A prolonged overall survival (OS) vs D. Patients were stratified (time from prior systemic chemotherapy; Bellmunt criteria) and randomized in a 1:1 ratio. D was administered for up to 10 cycles in both arms. OGX-427 maintenance continued in pts with no disease progression. Secondary objectives included safety, objective response, and serum levels of Hsp27. The trial design provided 90% power to detect a 33% decrease in OS hazard (hazard ratio [HR] = 0.667), with one-sided α = 0.10 after 162 deaths, and one interim futility analysis; a p-value < 0.1 would result in a positive study for the primary endpoint. Results: 200 pts were randomized between 8/2013 and 9/2015. 72.5% had 1-3 Bellmunt risk factors and 43.5% were < 3mos from prior chemotherapy. 163 pts had died (77 A+D; 86 D) at final analysis. The A+D group had a statistically-significant reduction in hazard for death vs. D (HR = 0.80; 80% CI, 0.65 to 0.98; one-sided P = 0.08). For A+D, median OS was 6.4 mos (95%CI 4.6-9.2) and 12-mo OS was 34.4% (95% CI 25.1-43.9). For D, median OS was 5.9 mos (95%CI 4.8-7.3) and 12-mo OS was 25.0% (95%CI 17.0-33.8). All causality grade 3 or higher toxicities were similar between A+D group (82%; 95%CI 73%-89%) and the D group (75%; 95%CI 65%-83%). The treatment effect of pts with baseline serum Hsp27 < 5.7ng/mL (median) vs. Hsp27 ≥ 5.7ng/mL was not different (2-sided p = 0.87 for interaction). Conclusions: In this platinum-pretreated population of advanced UC, adding OGX-427 to D provided a statistically significant improvement in OS and is worthy of further investigation in previously treated metastatic UC pts. Clinical trial information: NCT01780545.
ASCO Publications