APR-246, a new class anticancer compound in phase l/lla clinical trials.

TPS183 Background: APR-246 belongs to a new class of small molecules that is currently being tested in a phase I/IIa clinical trial. The goal of the study is to evaluate safety and pharmacokinetic (PK) properties of APR-246, but efficacy parameters will also be included. APR-246 has been shown to restore nonfunctional p53 by promoting its correct folding (Lambert et al. Cancer Cell 15, 2009). This represents a new strategy with potential to treat patients resistant to conventional chemotherapy. APR- 246 has been tested in a full nonclinical safety package and has shown no toxicity at predicted therapeutic plasma levels. This profile is further supported by the tumor specificity of APR-246 demonstrated in ex vivo studies with primary cells. Methods: The ongoing phase I/IIa trial was initiated in June 2009 and is an open labeled, dose-escalating study on refractory hematological malignancies and prostate cancer. The study will comprise approximately 25 patients, and is performed at 7 sites in Sweden. Each p...