Date: 2014-09-27
Type of information: Presentation of results at a congress
phase: 2
Announcement: presentation of results at the 2014 Congress of the European Society for Medical Oncology (ESMO)
Company: Ipsen (France) Active Biotech (Sweden)
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: advanced or metastatic hepato-cellular, ovarian, renal cell and gastric carcinomas in patients who have progressed after standard anti-tumor therapies
Therapeutic area: Cancer - Oncology
Country:
Trial
details: The UMBRELLA study is designed as a multi-center, open-label, early stopping design, proof of concept study. Tasquinimod clinical activity will be measured by the proportion of patients with progression free survival at pre-defined time-points.
Latest
news: * On 27 September 2014, Ipsen announced the presentation at the ESMO 2014 Congress (26-30 September in Madrid) of the preliminary results of the phase II proof-of-concept clinical trial with tasquinimod in monotherapy, evaluating the compound in four advanced tumor types. The main objective of the study was to determine the clinical activity of tasquinimod in advanced * On October 19, 2012, Ipsen has announced that it will shortly initiate a new phase II, proof-of-concept clinical trial with tasquinimod in a so-called umbrella study evaluating the compound in four different tumor types. The study will 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 anti-tumor therapies.
hepatocellular (HCC), ovarian (OC), renal cell (RCC) and gastric (GC) carcinomas in patients who had progressed after standard anti-tumor therapies. Primary endpoint was the PFS rate at a predefined time for each cohort. Secondary objectives included PFS, response rate, OS, safety, pharmacokinetics and biomarkers.
The data did not support further development of tasquinimod in monotherapy in heavily pretreated patients with advanced OC, RCC and GC. Pharmacokinetic and biomarkers analyses are ongoing.
Preliminary results from the futility analysis reported sufficient clinical activity to complete the recruitment of the HCC cohort for which results are expected in 2015.
The safety profile was consistent with the known safety profile of tasquinimod in previous studies. Data from the HCC cohort was presented (Poster p-171)1 at the International Liver Cancer Association 8th Annual Conference (5–7 September 2014, Kyoto, Japan).
Tasquinimod’s unique mode of action is highly relevant to target multiple malignant diseases beyond prostate cancer. The compound’s immunomodulatory and anti-angiogeneic properties are believed to be pertinent in addressing unmet medical need in a broad wealth of carcinomas.
Until today the development of tasquinimod was focused on the treatment of prostate cancer. Several clinical studies are currently ongoing:
• A phase III placebo-controlled study in men with bone-metastatic castration resistant prostate cancer
(mCRPC) adequately powered to detect an overall survival improvement. The phase III studywill 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.
• A Proof Of Concept “switch maintenance” Phase II clinical trial aiming at establishing the clinical efficacy of tasquinimod used as maintenance therapy in patients with metastatic castrate-resistant prostate cancer (mCRPC) who have not progressed after a first line docetaxel based chemotherapy. This is a randomized, double-blind placebo controlled, phase II trial investigating up to 1 mg/day of tasquinimod versus placebo in about 150 patients. The primary endpoint of the study is radiological progression free survival. The study will be recruited across about 50 centers in Europe.
• A Phase I investigator-sponsored clinical trial with the primary objective to determine the recommended dose of tasquinimod in combination with cabazitaxel based on safety and tolerability in heavily pretreated men with mCRPC. Secondary objectives include efficacy as measured by progression-free survival (PFS), and overall survival (OS). The study will include about 30 patients.
Additionally, a previous Phase II placebo-controlled study in men with asymptomatic/mildly symptomatic metastatic castration resistant prostate cancer, showed a higher fraction of patients with no disease progression during the six-month period of treatment using tasquinimod. These Phase II results were published in Journal of Clinical Oncology in September 2011. In June, 2012, overall survival (OS) datawas presented at ASCO (American Society of Clinical Oncology).
