Topline results announced today from the phase III Swedish trial 10TASQ10 demonstrated that tasquinimod failed to extend overall survival (OS) in men with metastatic castrate-resistant prostate cancer (mCRPC; HR=1.09; CI 95%, 0.94-1.28). The findings prompted the manufacturers, Active Biotech and Ipsen, to discontinue all studies in prostate cancer involving the agent, according to a joint statement.
reported on the results of a phase II trial that showed a prolonged progression-free survival (PFS) and OS with tasquinimod in certain men with mCRPC.1
Men in that trial were followed for a median of 37 months. At the time, researchers suggested the agent may provide a survival advantage in this setting, particularly among men with skeletal metastases.
“The outcome of the 10TASQ10 study is a major disappointment based on the promising phase II results,” Tomas Leanderson, president and chief executive officer of Active Biotech said in a statement. "However, the data at hand are unambiguous and cannot motivate further development of tasquinimod in this patient population.”
Although the antiangiogenic agent did not improve OS, it did reduce the risk of radiographic cancer progression or death compared to placebo (HR = 0.69; 95% CI, 0.60-0.80). Full results will be presented at an upcoming scientific conference.
The phase III trial enrolled approximately 1200 patients with metastatic CRPC. Patients were randomly assigned in a 2:1 ratio to 1 of 2 treatment groups: Treatment Group A (tasquinimod 0.25, 0.5, or 1 mg/day; n = 800) or Treatment Group B (placebo; n = 400). The primary endpoint was radiological PFS and OS was the secondary endpoint.
To be included in the study, men had to have a histologically confirmed diagnosis of adenocarcinoma of the prostate, evidence of bone metastatic disease on radiographic examination, evidence of progressive disease, and Karnofsky score ≥70%.
Men were excluded if they had undergone previous anticancer therapy using radiation, biologics or vaccines, including abiraterone, TAK-700, or MDV3100; previous therapy with antiandrogens within 4 weeks (within 6 weeks for bicalutamide) prior to study treatment; concurrent use of other anticancer agents or treatments, except for luteinizing hormone-releasing hormone agonists or antagonists, denosumab, or bisphosphonate.
The study involved 205 sites worldwide, including the United States (NCT01234311), with identical study requirements and design.
Current treatment options for men with mCRPC include sipuleucel-T, docetaxel, cabazitaxel, and/or abiraterone acetate, all of which have been shown to improve OS. However, treatments that slow metastatic progression and postpone the need for chemotherapy “are sought by both patients and healthcare providers,” investigators said in discussing the initial results of the phase II trial.
Tasquinimod is a novel oral immunotherapy that targets the tumor microenvironment by binding to S100A9 and modulating regulatory myeloid cell functions, and exerting immunomodulatory, antiangiogenic and antimetastatic properties.
According to the statement, 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.
Armstrong AJ, Häggman M, Stadler WM, et al. Long-term survival and biomarker correlates of tasquinimod efficacy in a multicenter randomized study of men with minimally symptomatic metastatic castration-resistant prostate cancer. Clin Cancer Res. 2013;19:6891-6901.