A phase II study of preoperative figitumumab (F) in patients (pts) with localized prostate cancer (PCa).

Abstract

4662 Background: F is a fully human IgG2 monoclonal antibody against insulin- like growth factor-1 receptor (IGF1R). Activation of the IGF1R pathway is implicated in PCa progression. This study evaluated biologic and clinical effects of F in pts with treatment-naive localized PCa. Methods: Pts received F 20 mg/kg IV q3 weeks for 3 cycles. Radical prostatectomy was performed within 1 week of last dose. Single center, 1-stage design with primary endpoint of IGF1R expression inhibition by immunohistochemistry (IHC) (H0<5%, H1>30%, α=0.05, β=0.1). Additional studies included: serial PSA, serum IGF1 by ELISA, granulocyte IGF1R expression by flow cytometry, IHC of IGF1R downstream effectors and androgen receptor, and F tissue level. Results: Accrual completed 10/2009 with 16 pts. Baseline characteristics: median age 63 years (range 50-71), cT1:cT2 = 4:14 pts, Gleason score 6:7:9 = 1:14:1 pts, median PSA 7.2 (range 2.5-35). Post-op stage was pT2:pT3:pN1 in 5:9:1 pts and Gleason score 7:8:9 in 9:3:2 pts. 14 pts received 3 cycles, 2 pts received 1 cycle (1 pt choice, 1 grade 3 hyperglycemia in a pt with diabetes) with no F-related post-op adverse events. For all 16 pts a pre-op PSA decline from baseline by ≥25%, ≥30% and ≥50% occurred in 15 (94%), 14 (88%) and 5 (31%) pts respectively. Serum IGF1 increased by a mean 4.8 fold (P<0.001). Granulocyte IGF1R expression decreased in 13 of 14 pts with a mean change of -34% (range -54% to +17%, P<0.001). Preliminary IGF1R IHC results for 6 matched biopsy/prostatectomy specimens currently analyzed show that all had decreased IGF1R expression by visual score (based on % of cells with staining intensity 0-3): in pre-F and post-F PCa the mean IGF1R IHC score was 1.9 and 0.8 respectively (P=0.006), and the mean % of cells with IHC intensity score of 0-1 increased from 25% Pre-F to 92% post-F (P=0.003). Analyses will be completed on all tissues by 04/2010. Conclusions: F prior to prostatectomy was well tolerated. Single agent biologic and clinical activity was observed with compensatory serum IGF1 increase, decreased IGF1R expression on granulocytes and PCa tissues, and a high rate of PSA declines. These results support the clinical relevance of IGF1R signaling in PCa and justify further clinical trials. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer Pfizer Pfizer