Date: 2016-09-28
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the European Cancer Congress (ECC 2015) held in Vienna
Company: Active Biotech (Sweden) Ipsen (France)
Product: 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: metastatic castrate-resistant prostate cancer (CRPC)
Therapeutic area: Cancer - Oncology
Country: Australia, Belgium, Brazil, Bulgaria,Canada, Chile, China, Colombia, Czech Republic, Estronia, France, Germany, Greece, India, Israel, Italy, Republic of Korea, Latvia, Lebanon, Lithuania, Mexico, New Zealand, The Netherland, Panam, Peru, Poland, Romania, Russian Federation, Slovakia, Spain, Sweden, Taiwan, Turkey,Ukraine, UK,USA
Trial
details: The 10TASQ10 trial is a randomized, double-blind, placebo-controlled, global Phase III clinical trial which evaluated tasquinimod in patients with metastatic castration resistant prostate cancer (mCRPC) who had not yet received chemotherapy. The aim of the 10TASQ10 study was to confirm tasquinimod's efficacy, with radiological Progression Free Survival (rPFS) as primary endpoint and overall survival (OS) as key secondary endpoint. In April 2015, top line data was presented which showed that tasquinimod reduced the risk of radiographic cancer progression or death compared to placebo (rPFS, HR=0.69, CI 95%: 0.60 - 0.80) in patients with metastatic castration resistant prostate cancer (mCRPC) who have not received chemotherapy, but did not extend overall survival (OS, HR=1.09, CI 95%: 0.94 - 1.28). The efficacy results did not support positive benefit risk balance in this patient population. (NCT01234311)
Latest
news: * On September 28, 2015, Active Biotech announced at the European Cancer Congress (ECC 2015) held in Vienna 25-29 September, the presentation of final results from the 10TASQ10 tasquinimod phase 3 trial. Final results show that tasquinimod treatment resulted in a prolonged radiographic progression free survival (rPFS), 7.0 vs. 4.4 months (central assessment) similar to an earlier Phase 2 study. However, the positive effect on rPFS did not translate into an improved OS (HR 1.097, 95% CI: 0.938-1.282). Tasquinimod safety was in general manageable and similar to what was observed during the Phase 2 study. The abstract "A phase 3, randomized, double-blind, placebo-controlled study of tasquinimod (TASQ) in men with metastatic castrate resistant prostate cancer (mCRPC), M. Carducci et al" was selected by the 18th ECCO - 40th ESMO European Cancer Congress Scientific Committee as a Best Abstract presentation in a Presidential Session (28 September 2015 at 2:35 pm CEST). * On December 10, 2012, Active Biotech and Ipsen have announced that the Phase III clinical trial for tasquinimod is successfully enrolled with over 1,200 randomized patients as planned in the clinical protocol. This achievement triggers a €10 million milestone payment from Ipsen to Active Biotech. The study recruited patients in more than 250 centers all over the word. It was announced in December 2009 that the primary endpoint of the Phase II clinical study, to show a higher fraction of patients with no disease progression during the six-month period of treatment using tasquinimod, had been met. Phase II results were published in Journal of Clinical Oncology in September 2011. The results showed that 6 month progression-free proportions for TASQ and placebo groups were 69% and 37%, respectively (p<.0001). The median progression free survival was 7.6 months for the tasquinimod group, compared to 3.3 months for the placebo group (p=0.0042). Analysis of up to three years safety data from the Phase II study, presented at the EAU February 2012, show that 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. In June, 2012, overall survival (OS) data was presented at ASCO (American Society of Clinical Oncology). In October, 2012, biomarker data were presented at the scientific congress ESMO (European Society for Medical Oncology). The results support an effect of tasquinimod on both immunomodulation and angiogenesis positioning tasquinimod as a potentially unique therapeutic approach with a mechanism of action that does not target the androgen receptor pathway. Also, in October 2012, the independent Data and Safety Monitoring Board (DSMB monitoring the ongoing Phase III trial, recommended that the study continues in accordance with the protocol since no safety-related issues were noted. A new Phase II, proof-of-concept clinical trial was initiated and which aims at establishing the clinical efficacy of tasquinimod used as maintenance therapy in patients with mCRPC who have not progressed after a first-line docetaxel based chemotherapy. Ipsen has also initiated an innovative Phase II proof-of-concept clinical trial with tasquinimod, to evaluate the safety and efficacy of tasquinimod in advanced or metastatic hepato-cellular, ovarian, renal cell and gastric carcinomas in patients who have progressed after standard therapies. * On May 21, 2012, Active Biotech and Ipsen have announced that recruitment to the global, pivotal, randomized, double-blind, placebo-controlled phase III study of tasquinimod in patients with metastatic castrate-resistant prostate cancer (CRPC) has reached an inclusion of 600 patients, half of the planned accrual. This triggers a €10 million milestone payment from Ipsen to Active Biotech. The aim of the Phase III study is to confirm tasquinimod’s efficacy on metastatic CRPC in the prechemotherapy setting, with radiological progression free survival (PFS) as the primary endpoint and overall survival (OS) as secondary endpoint. 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. Today the development of tasquinimod is principally focused on the treatment of prostate cancer. It was announced in December 2009 that the primary endpoint of the Phase II clinical study, to show a higher fraction of patients with no disease progression during the six-month period of treatment using tasquinimod, had been met. Phase II results were published in Journal of Clinical Oncology in September 2011 (Phase II Randomized, Double-Blind, Placebo-Controlled Study of Tasquinimod in Men With Minimally Symptomatic Metastatic Castrate-Resistant Prostate Cancer. Roberto Pili et al. JCO Oct 20, 2011:4022-4028; published online on September 19, 2011; 10.1200/JCO.2011.35.6295). It was concluded that tasquinimod significantly slowed disease progression and improved Progression Free Survival (PFS) in chemonaïve patients with metastatic castrate-resistant prostate cancer, alongside an acceptable side effect profile. Six month progression free proportion of patients for TASQ and placebo treatment groups were 69% and 37%, respectively (p<0.0001), with a median PFS of 7.6 vs. 3.3 months (p=0.0042). Analysis of up to three years safety data from the Phase II study, presented at the EAU February 2012, show that 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. Preliminary overall survival data was released on May 18, 2012 which showed that median time to death was 34.2 vs. 30.2 months (tasquinimod vs placebo). A preliminary subgroup analysis using the PCWG2 (Prostate Cancer Clinical Trials Working Group 2) defined criteria showed that median time to death in the bonemetastatic subgroup was 34.2 vs. 25.6 months (tasquinimod vs placebo).
* On April 16, 2015, Active Biotech and Ipsen announced top line results of the 10TASQ10 study. While the study showed that tasquinimod reduced the risk of radiographic cancer progression or death compared to placebo (rPFS, HR=0.69, CI 95%: 0.60 – 0.80) in patients with metastatic castration resistant prostate cancer (mCRPC) who have not received chemotherapy, tasquinimod did not extend overall survival (OS, HR=1.09, CI 95%: 0.94 – 1.28). Efficacy results together with preliminary safety data do not support positive benefit risk balance in this population. Therefore the companies have decided to discontinue all studies in prostate cancer. Full results will be presented at an upcoming scientific conference. Ipsen and Active Biotech are in communication with trial investigators, ethics committees and the relevant regulatory authorities, to provide them with updated and current information in compliance with local regulations. The companies are working with trial investigators and local regulatory authorities to ensure that patients who participated in the tasquinimod trials are transitioned to appropriate therapies so that trial participants receive appropriate care.
