918P - Phase 2 results from a phase 1/2 study of TAK-700 (orteronel), an oral, investigational, nonsteroidal 17,20-lyase inhibitor, with docetaxel and pred...

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Drug Development
Prostate Cancer
Presenter Daniel Petrylak
Authors D.P. Petrylak1, J.G. Gandhi2, W.R. Clark3, E.I. Heath4, J. Lin5, W.K. Oh6, D.B. Agus7, B. Carthon8, S. Moran9, G. Liu10
  • 1Oncology, Columbia University Medical Center, 10032 - New York/US
  • 2Oncology And Hematology, Associates in Oncology and Hematology, 37404 - Chattanooga/US
  • 3Oncology, Alaska Clinical Research Center, 99508 - Anchorage/US
  • 4Oncology, Karmanos Cancer Institute, 48201 - Detroit/US
  • 5Medical Oncology, Thomas Jefferson University, 19107 - Philadelphia/US
  • 6Oncology, Mt. Sinai Hospital, 10029 - New York/US
  • 7Molecular Medicine, University of Southern California, Keck School of Medicine, 90211 - Beverly Hills/US
  • 8Hematology, Winship Cancer Institute, Emory University, 30322 - Atlanta/US
  • 9Oncology, Millennium Pharmaceuticals, Inc., 02139 - Cambridge/US
  • 10Oncology, University of Wisconsin Carbone Cancer Center, 53792 - Madison/US



The investigational agent TAK-700 (orteronel) is a selective 17,20-lyase inhibitor that blocks androgen production. Since DP is currently standard chemotherapy in mCRPC, this phase 1/2 study examined TAK-700 + DP in men with mCRPC.


The primary phase 2 objective is tolerability of TAK-700 400 mg BID + D (75 mg/m q3w) + P (5 mg BID) in castrate men (testosterone [T] <50 ng/dL) with mCRPC, no prior chemotherapy and no ketoconazole/abiraterone ≤30 d prior. Secondary objectives were PK, PSA response rates after 3 mo, best PSA response at any time, time to progression of PSA ± radiographic disease, response by RECIST 1.1. D was started on d8 of cycle 1 (28 d); cycles ≥2 = 21 d.


24 men were treated: median age was 66 yrs (range 53–87), ECOG PS 0/1 (88%/12%). At baseline, median PSA was 47 ng/mL (4.5–813) and T was 7.2 ng/dL (3.2–13.8). At data cutoff, 15/24 men remained on study treatment. 22/24 men experienced a treatment-related AE. 3 men discontinued due to AEs (ALT increase, arthralgia, pneumonitis). 21 men (88%) had at least 1 Gr ≥3 AE (19 were drug-related). Drug-related Gr ≥3 AEs ≥10% were WBC decreased (29%); neutropenia (25%); decreased neutrophil count (25%); fatigue, and febrile neutropenia (each 13%). The most common drug-related SAE was febrile neutropenia (13%). As of cutoff, there were no on-study deaths. At 3 mo, PSA30, PSA50, and PSA90 rates in the PSA evaluable population were 59%, 50%, and 18%, respectively. Best PSA decline (median) was -76% (n = 22; -99 to +144%). Median T at 3 mo decreased to ≤0.2 ng/dL (0.3–10.6). Best ORR 50% (n = 10; 80% CI: 27,73; partial response in 5 of 10 evaluable men). Median time to PSA progression was 6.1 mo (95% CI: 4.6, not reached) and median time to radiologic progression was not reached. The Cmax of DP + TAK-700 was similar to that of DP alone.


TAK-700 400 mg BID + DP appears tolerable and shows androgen-lowering activity and strong PSA and partial tumor response in mCRPC. Plasma levels of D administered with TAK-700 + P were similar to published data on DP without TAK-700.


D.P. Petrylak: Consultant/Advisor: Amgen, Bayer, Pfizer, Ferring, Millennium, Novartis, Dendreon, Johnson & Johnson, Glaxo Smith Kline Research funding: Celgene, Dendreon, Sanofi, Pfizer, AstraZenca, Glaxo Smith Kline, Rogosen institute, Boehringer Ingelheim,

W.R. Clark: Investigator for BMS, Millenium, Lily, Watson, Roll International, Astellas,

E.I. Heath: Research funding: Millennium Pharmaceuticals, Ltd.

W.K. Oh: Advisor/consultant: Amgen, Pfizer, Sanofi, Dendreon, Bellicum, and Medivation,

D.B. Agus: Millenium Pharmaceuticals, Inc./Takeda Advisory Board,

S. Moran: Employment: Millennium Pharmaceuticals, Inc.

All other authors have declared no conflicts of interest.