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  • Vink, P.; Torrell, J.M.R.; Fructuoso, A.S.; Kim, Sung-Joo; Kim, Sang-Il; Zaltzman, J.; Ortiz, F.; Plana, J.M.C.; Rodriguez, A.M.F.; Rodrigo, H.R.; Marti, M.C.; Perez, R.; Roncero, F.M.G.; Kumar, D.; Chiang, Y.-J.; Doucette, K.; Pipeleers, L.; Morales, M.L.A.; Rodriguez-Ferrero, M.L.; Secchi, Antonio; McNeil, S.A.; Campora, L.; Di Paolo, E.; El Idrissi, M.; López-Fauqued, M.; Salaun, B.; Heineman, T.C.; Oostvogels, L. (2020)
    Background. The incidence of herpes zoster is up to 9 times higher in immunosuppressed solid organ transplant recipients than in the general population. We investigated the immunogenicity and safety of an adjuvanted recombinant zoster vaccine (RZV) in renal transplant (RT) recipients ≥18 years of age receiving daily immunosuppressive therapy. Methods. In this phase 3, randomized (1:1), observer-blind, multicenter trial, RT recipients were enrolled and received 2 doses of RZV or placebo 1-2 months (M) apart 4-18M posttransplant. Anti-glycoprotein E (gE) antibody concentrations, gE-specific CD4 T-cell frequencies, and vaccine response rates were assessed at 1M post-dose 1, and 1M and 12M post-dose 2. Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days after each dose, respectively. Solicited general symptoms and unsolicited AEs were also collected 7 days before first vaccination. Serious AEs (including biopsy-proven allograft rejections) and potential immune-mediated diseases (pIMDs) were recorded up to 12M post-dose 2. Results. Two hundred sixty-four participants (RZV: 132; placebo: 132) were enrolled between March 2014 and April 2017. gE-specific humoral and cell-mediated immune responses were higher in RZV than placebo recipients across postvaccination time points and persisted above prevaccination baseline 12M post-dose 2. Local AEs were reported more frequently by RZV than placebo recipients. Overall occurrences of renal function changes, rejections, unsolicited AEs, serious AEs, and pIMDs were similar between groups. Conclusions. RZV was immunogenic in chronically immunosuppressed RT recipients. Immunogenicity persisted through 12M postvaccination. No safety concerns arose. © The Author(s) 2019.
  • Shore, Neal D.; Tammela, Teuvo L.; Massard, Christophe; Bono, P.; Aspegren, John; Mustonen, Mika; Fizazi, Karim (2018)
    Background: ODM-201, a new androgen receptor antagonist for treatment of metastatic castration-resistant prostate cancer (mCRPC), demonstrated antitumour activity and acceptable tolerability in phase 1/2 trials. Objective: To determine the antitumour activity and safety profile of extended treatment with ODM-201 in men with mCRPC. Design, setting, and participants: ARADES and ARAFOR trials with ODM-201 enrolled chemotherapy-naïve and CYP17 inhibitor (CYP17i)-naïve mCRPC patients. Both trials had extended follow-up. Here we report results for chemotherapy-naïve and CYP17i-naïve patients from both trials (data cutoff October 2014 for ARADES and April 2015 for ARAFOR) after extended follow-up. Intervention: A total of 41 chemotherapy-naïve and CYP17i-naïve patients received oral ODM-201 twice daily (total daily dose of 1200, 1400 or 1800 mg). Outcome measurements and statistical analysis: Antitumour activity was assessed in terms of prostate-specific antigen (PSA) declines and PSA/radiographic progression. Safety was assessed until disease progression and/or drug discontinuation due to any intolerable adverse event (AE). Results and limitations: ODM-201 safety data after a median treatment time of 13.5 mo (95% confidence interval [CI] 9.7–15.6, interquartile range [IQR] 7.5–22.0) were similar to those reported in the main ARADES and ARAFOR trials. The overall AE incidence was 80.5% (n = 33/41), with 58.5% (n = 24/41) of patients experiencing only grade 1–2 AEs. The most common AEs were fatigue, back pain, diarrhoea, nausea, and pain in extremity. The median times to PSA and radiological progression were 12.4 mo (95% CI 6.3–18.2, IQR 5.5–22.0) and 15.3 mo (95% CI 9.5–not reached [NR], IQR 6.3–NR), respectively. Conclusions: Extended treatment with ODM-201 (1200–1800 mg/d) was well tolerated, with no new safety concerns, and provided evidence of sustained antitumour activity in chemotherapy-naïve and CYP17i-naïve patients with mCRPC. Patient summary: Prolonged treatment with high doses of ODM-201 was well tolerated and provided long-lasting disease control in patients with mCRPC. ODM-201 represents a therapeutic treatment option for mCRPC. The ARAFOR trial (including the follow-up stage) and the follow-up component of the ARADES trial are registered with ClinicalTrials.gov as trial numbers NCT01784757 and NCT01429064. Extended treatment with ODM-201 was well tolerated and provided long-lasting disease control in chemotherapy- naïve and CYP17 inhibitor-naïve patients with metastatic castration-resistant prostate cancer (mCRPC). ODM-201 may represent an additional effective treatment option for mCRPC. © 2017 European Association of Urology
  • Fizazi, Karim; Massard, Christophe; Bono, P.; Kataja, Vesa; James, Nicholas; Tammela, T.L.; Joensuu, H.; Aspegren, John; Mustonen, M. (2017)
    Background: Patients with castration-resistant prostate cancer (CRPC) had extended responses to the androgen receptor antagonist ODM-201, in phase 1/2 studies. Objective: To evaluate the safety and antitumour activity of prolonged ODM-201 treatment in patients with CRPC. Design, setting, and participants: The ARADES trial was a multicentre phase 1 (dose escalation) and phase 2 (dose expansion) trial; 134 patients with CRPC were stratified by previous chemotherapy to receive ODM-201. This paper reports extended follow-up in CYP17 inhibitor (CYP17i)-naïve patients. Intervention: Patients (n = 77) received oral ODM-201 twice daily at daily doses of 200–1800 mg. Outcome measurements and statistical analysis: Safety, measured as the occurrence of adverse events (AEs), prostate-specific antigen (PSA), and radiographic progression. Results and limitations: The safety profile of extended ODM-201 treatment (median treatment duration 8.2 mo, 95% confidence interval [CI] 5.6–11.0) was consistent with that reported at the time of the original data cutoff in the main ARADES trial, with no unexpected safety concerns over time. The majority of AEs (61.1%) were mild (grade 1); the most common AE was fatigue/asthenia (35.1% of patients), with no clear relationship to ODM-201. Median time to PSA progression was 25.2 mo (95% CI 11.3–25.2) for chemotherapy-naïve men and not reached (NR; 95% CI 5.5–NR) for chemotherapy-pretreated patients; a trend for improved antitumour response was observed for chemotherapy-naïve patients. The median time to radiographic progression was longer for chemotherapy-naïve (14.0 mo, 95% CI 8.1–33.3) than for chemotherapy-pretreated (7.2 mo, 95% CI 2.7–11.0) patients. Conclusions: Prolonged exposure to ODM-201 was well tolerated, with no additional safety concerns; disease suppression was sustained, especially in chemotherapy-naïve patients. These data support further development of ODM-201 in men with CYP17i-naïve CRPC. Patient summary: Extended ODM-201 therapy was well tolerated, with beneficial antitumour activity in men with advanced prostate cancer, indicating that ODM-201 may represent a new active treatment for men with CRPC. This extension trial is registered at ClinicalTrials.gov (www.clinicaltrials.gov) under identification number NCT01429064. Extended ODM-201 therapy showed encouraging antitumour activity in both chemotherapy-naïve and chemotherapy-treated men with metastatic castration-resistant prostate cancer (CRPC). Continued treatment with ODM-201 was well tolerated, with no unexpected safety concerns, and may represent a new, effective treatment option for men with CRPC. © 2017 European Association of Urology