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OM-RCA-01, an FGFR1 specific humanized antibody for the treatment of renal cell carcinoma (RCC).
Developmental Therapeutics - Experimental Therapeutics
Session Type and Session Title:
General Poster Session, Developmental Therapeutics - Experimental Therapeutics
J Clin Oncol 30, 2012 (suppl; abstr 3070)
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
Background: Fibroblast growth factor (FGF) receptor 1 (FGFR1) is a potential therapeutic target for the treatment of metastatic RCC. We investigated the preclinical activity of OM-RCA-01, a novel therapeutic humanized anti-FGFR1 antibody with high affinity (Kd of 1.59 nM), in RCC. Methods: To assess the effect of anti-FGFR1 antibody on FGF-mediated signaling, the human renal carcinoma Caki-1 FGFR1-expressing cells were dosed with OM-RCA-01 at 100, 10, and 1 mcg/ml. Control wells were left untreated. Three hours after dosing, bFGF was added at a concentration of 50 ng/ml. Additional control wells were treated with OM-RCA-01 without FGF-stimulation. Cell growth inhibition was determined using Promega’s Cell Titer-Glo assay. CR female NCr nu/nu mice were set up with 1 mm3 Caki-1 tumor fragments sc in flank. Tumor sizes were measured in a blind fashion twice a week with a vernier caliper. Mice with established tumors were randomly divided into vehicle, non-specific IgG or OM-RCA-01 groups per 10 animals in group. Endpoint was significant differences in tumor growth delay. Results: In vitro study showed that bFGF increased proliferation of the human FGFR1-expressing renal carcinoma cells (p=0.011). OM-RCA-01 antibody significantly inhibits FGF-triggered cell proliferation in comparison with control. In vivo, the tumors in untreated mice or mice treated with non-specific IgG continued their aggressive growth to reach the size of 2000 cm3, at which point the mice were killed. In contrast, treatment with OM-RCA-01 not only significant arrested further growth of the tumors (p=0.006) but also demonstrated differences in tumor volume compared with vehicle already on Day 13. A similar anti-tumor activity of OM-RCA-01 was observed when the antibody was given in low (1 mg/kg) or high (10 mg/kg) doses (p=0.917). Administration of 10 mg/kg antibody for up to 35 days resulted in minimal body weight loss and no observations of gross toxicity were made. Conclusions: Targeting FGFR1 blocks FGF/FGFR1 pathway in RCC. Monoclonal antibody OM-RCA-01 has significant early anti-tumor efficacy in Caki-1 xenograft model. Isolated blocking of FGFR1 by low-dose antibody could be safe and effective.