Phase I study of CNTO 95, a fully human monoclonal antibody to αv integrins, docetaxel, and prednisone in hormone refractory prostate cancer patients (HRPCP)

Abstract

15595 Background: CNTO 95 has demonstrated preclinical antitumor activity through binding to multiple av integrins, resulting in growth inhibition indirectly through anti-angiogenic effects as well as directly by inhibiting tumor cell proliferation. The target, av integrins, has been demonstrated by immunohistochemistry in a large proportion of human prostate cancer tissues. Docetaxel and prednisone have become a standard of care for HRPCP. The primary objective of this study was to evaluate the safety of combining CNTO 95 with this standard. Methods: Patients received day 1 infusions of 75 mg/m2 docetaxel together with twice daily oral prednisone in every 3 week cycles, with weekly infusions of either 5 or 10 mg/kg of CNTO 95 for 7 weeks beginning with the second docetaxel cycle, then CNTO 95 on the days of docetaxel thereafter. Patients were monitored for safety and PSA. Radiologic tumor assessments were performed at least every 4 cycles. Results: Six patients have received docetaxel and prednisone with CNTO 95 at either 5 mg/kg (n=3) or 10 mg/kg (n=3). In the 5 mg/kg group, 1 received 8 cycles then withdrew consent because of fluctuating PSA levels; 1 received 9 cycles then had soft tissue disease progression; and 1 has completed 9 cycles and remains on study treatment. In the 10 mg/kg group, all patients remain on study and have received 7, 6, and 6 cycles of treatment, respectively. There were no unexpected toxicities and only one Grade 3 toxicity (febrile neutropenia) attributed to docetaxel. A 50% decline in PSA occurred in 1 patient treated in the 10 mg/kg group. Conclusions: The combination of standard dose docetaxel and prednisone with 10 mg/kg of CNTO 95 was well tolerated and 3 new patients are planned to be treated with these doses on this study. Further study is warranted. [Table: see text]