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Pharmacokinetics, Antitumor Activity, and Safety of ODM-201 in Patients with Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer: An Open-label Phase 1 Study

2015; Elsevier BV; Volume: 69; Issue: 5 Linguagem: Inglês

10.1016/j.eururo.2015.09.046

1873-7560

Christophe Massard, Heidi Penttinen, Egils Vjaters, Petri Bono, Vilnis Lietuvietis, Teuvo L.J. Tammela, Annamari Vuorela, Pirjo Nykänen, Pasi Pohjanjousi, Amir Snapir, Karim Fizazi,

Hormonal and reproductive studies

ODM-201 is a novel second-generation androgen receptor inhibitor for the treatment of metastatic castration-resistant prostate cancer (mCRPC). To evaluate the pharmacokinetics of ODM-201 tablet products and preliminary long-term safety, tolerability, and antitumor activity of ODM-201 in chemotherapy-naive men with mCRPC. Thirty patients were enrolled in this open-label phase 1 trial. Patients received a single 600-mg dose of ODM-201 in capsules with food and one 600-mg dose of ODM-201 tablet product (TabA or TabB) with food and in the fasted state in a random order. In the extension, patients received 600 mg twice daily ODM-201 taken with food in capsules. We analyzed the pharmacokinetics of ODM-201 tablet formulations. Safety and tolerability were assessed until disease progression or an intolerable adverse event (AE). Antitumor activity was assessed by prostate-specific antigen (PSA) levels and imaging. The capsule:TabA ratio of area under the concentration-time curve from time zero to the last sample at 48 h was 1.06 (90% confidence interval [CI], 0.91–1.24); the capsule:TabB ratio was 0.97 (90% CI, 0.82–1.14). At week 12, 25 of 30 patients (83%) had a PSA response (≥50% reduction from baseline). Median time to radiographic progression was 66 wk (95% CI, 41–79). Most common AEs were fatigue (n = 4 [13%]) and nausea (n = 4 [13%]). The study showed that the tablet formulation of ODM-201 had similar pharmacokinetics compared with the capsule. Treatment with a 600-mg twice daily dose of ODM-201 provided anticancer activity and was well tolerated in men with chemotherapy-naive mCRPC. The findings of this study showed that ODM-201 is well tolerated and provided antitumor activity in chemotherapy-naive patients with metastatic castration-resistant prostate cancer (mCRPC) and that the 300-mg tablet formulation can be used in further clinical studies. A phase 3 trial with ODM-201 600 mg twice daily in patients with non-mCRPC is ongoing.