title: Pharmacokinetics, Antitumor Activity, and Safety of ODM-201 in Patients with Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer: An Open-label Phase 1 Study.
abstract: 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 600mg 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 48h 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 600mg twice daily in patients with non-mCRPC is ongoing.
authors.affiliation: Institut Gustave Roussy, University of Paris Sud, Villejuif, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Massard
authors.affiliation: Comprehensive Cancer Center, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland.
authors.forename: Heidi M
authors.initials: HM
authors.lastname: Penttinen
authors.affiliation: Stradins Clinical University Hospital, Riga, Latvia.
authors.forename: Egils
authors.initials: E
authors.lastname: Vjaters
authors.affiliation: Comprehensive Cancer Center, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland.
authors.forename: Petri
authors.initials: P
authors.lastname: Bono
authors.affiliation: Riga East University Hospital, Riga, Latvia.
authors.forename: Vilnis
authors.initials: V
authors.lastname: Lietuvietis
authors.affiliation: Tampere University Hospital and School of Medicine, University of Tampere, Tampere, Finland.
authors.forename: Teuvo L
authors.initials: TL
authors.lastname: Tammela
authors.affiliation: Orion Corporation, Orion Pharma, Espoo, Finland.
authors.forename: Annamari
authors.initials: A
authors.lastname: Vuorela
authors.affiliation: Orion Corporation, Orion Pharma, Espoo, Finland.
authors.forename: Pirjo
authors.initials: P
authors.lastname: Nykänen
authors.affiliation: Orion Corporation, Orion Pharma, Espoo, Finland.
authors.forename: Pasi
authors.initials: P
authors.lastname: Pohjanjousi
authors.affiliation: Orion Corporation, Orion Pharma, Espoo, Finland.
authors.forename: Amir
authors.initials: A
authors.lastname: Snapir
authors.affiliation: Institut Gustave Roussy, University of Paris Sud, Villejuif, France. Electronic address: karim.fizazi@gustaveroussy.fr.
authors.forename: Karim
authors.initials: K
authors.lastname: Fizazi
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019540:Area Under Curve; D002214:Capsules; D018592:Cross-Over Studies; D018450:Disease Progression; D005221:Fatigue / Q000139:chemically induced; D006801:Humans; D007465:Iodohippuric Acid; D008297:Male; D009325:Nausea / Q000139:chemically induced; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D011720:Pyrazoles / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D013607:Tablets
chemical_list: D000970:Antineoplastic Agents; D002214:Capsules; D011720:Pyrazoles; D013607:Tablets; C000607739:darolutamide; D007465:Iodohippuric Acid; D017430:Prostate-Specific Antigen
keywords: Androgen receptor inhibitor; Castration-resistant prostate cancer; ODM-201