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 Clinical research
Prostate Cancer
Basic Scientific Principles
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

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Disclosure

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.