Date: 2012-10-01
Type of information: Results
phase: 2
Announcement: results
Company: Active Biotech (Sweden) Ipsen (France)
Product: TASQ (tasquinimod)
Action
mechanism: immunomodulator/immunotherapy product. TASQ (tasquinimod, ABR-215050) binds to a molecule called S100A9 which is expressed in the white blood cells involved in the regulation of immune responses. S100A9 interacts with two known pro-inflammatory receptors (Toll like receptor 4 (TLR4) and receptor of advanced glycation end products (RAGE)) and this interaction is inhibited by TASQ (Björk et al PLoS Biology, April 2009).
Disease: castrate resistant prostate cancer
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On October 1, 2012, Active Biotech and Ipsen have presented a new set of data on biomarkers from the previously concluded tasquinimod Phase 2 study in chemotherapy-naïve metastatic castrate resistant prostate cancer (CRPC) at the scientific congress ESMO (European Society for Medical Oncology) held in Vienna September 28-October 2. The purpose of this analysis from the phase 2 trial was to investigate the effects of tasquinimod on selected biomarkers to confirm preclinical findings on the mechanism of action. The results support an effect of tasquinimod on both immunomodulation and angiogenesis which positions tasquinimod as a potentially unique therapeutic approach with a mechanism of action that does not target the androgen receptor pathway. The findings shall be further validated in the ongoing phase III placebo-controlled study in men with bone-metastatic CRPC, which has been adequately powered to detect an OS improvement. The study will include about 1,200 patients in more than 250 centers. Recruitment is proceeding according to plan with top line results expected by the end of 2013. In June 2012, overall survival (OS) data was presented at ASCO (American Society of Clinical Oncology) (See below)
* On June 4, 2012, Active Biotech and Ipsen have presented overall survival (OS) data from the tasquinimod Phase II study in chemotherapy-naïve metastatic castrate resistant prostate cancer (CRPC) at the scientific conference "2012 ASCO Annual Meeting" held in Chicago (USA). The intention-to-treat analysis showed median overall survival times (OS) of 33.4 vs. 30.4 months (p=0.49, HR 0.87, 95% CI 0.59-1.29, ITT) in favor of tasquinimod, longer than previously reported in this metastatic prostate cancer population. A stronger trend for survival benefit is observed in patients with bone metastases; median OS was 34.2 vs. 27.1 months (p=0.19, HR 0.73, 95% CI 0.46-1.17).
This phase II clinical trial was designed to test the safety and efficacy of tasquinimod. Noteworthy, 41 (61%) patients crossed-over from placebo to tasquinimod (mean time to cross-over approx. 5 months). Also, there were imbalances in baseline prognostic factor in favor of the placebo arm. These were addressed with a multivariate analysis of known CRPC prognostic factors. It demonstrated a statistically significant OS advantage for tasquinimod treated patients with a hazard ratio (HR) of 0.64 (95% CI 0.42-0.97, p=0.034), a decrease of approximately 40% in the instantaneous risk of event (death), accompanied by improvement in progression-free survival (HR 0.52, 95% CI 0.35-0.78, p=0.001).
* On February 24, 2012, Active Biotech's and Ipsen's castrate resistant prostate cancer project, TASQ will be presented at the 27th Annual EAU Congress held in Paris on 24-28 February 2012. The presentation will detail the analysis of up to three years safety data from the TASQ Phase II study in chemotherapy-naïve metastatic castrate resistant prostate cancer (CRPC). Treatment side effects were mild to moderate (~ 5% of AEs grade 3-4), manageable and less frequent after two months of therapy. The adverse events observed included gastrointestinal disorders, primarily observed initially during treatment, fatigue and musculoskeletal pain.
A global, pivotal, randomized, double-blind, placebo-controlled Phase III study of TASQ in patients with metastatic CRPC is ongoing. The aim of the study is to confirm TASQ's effect on the disease, with radiological PFS as the primary endpoint and overall survival as secondary endpoint. The study will include about 1,200 patients in more than 250 clinics. The independent Data and Safety Monitoring Board (DSMB) overseeing the ongoing Phase III clinical trial has recommended the study to proceed as per protocol as no safety concern were identified. The poster is available on http://activebiotech.com/file/poster-tasq-eau-2012-final-120120.pdf)
