Abstract A138: Extracellular FGFR1 inhibition with OM-RCA-01 humanized antibody suppresses tumor growth in FGFR1-expressing colorectal cancer models

Abstract Background: Fibroblast growth factor receptor (FGFR) signaling in colorectal cancer (CRC) can be driven by ligand-dependent activation of its extracellular domains. We hypothesized that selective targeting of the extracellular II–IIIc domains using OM-RCA-01 - a humanized monoclonal antibody against FGFR1 - may offer an effective therapeutic strategy in FGFR1-expressing CRC. Methods: In vitro, SW620 cells were treated with OM-RCA-01 (2×10-4 to 1.25×10-5 g/ml, serial 1:2 dilutions), followed by FGF2 (5 ng/ml), and cell proliferation was assessed. Additionally, metastatic tumor tissue surgically resected from FGFR1-expressing CRC patients (Cell Signaling) was rinsed in PBS containing antibiotics/antimycotics, then mechanically minced. Cell culture was incubated in the presence of FGF2 (50 ng/ml), following the protocol described by Otte et al. (Sci Rep, 2019). To assess FGFR1 inhibition, OM-RCA-01 was added to the culture medium at a concentration of 30 µg/ml. DMSO was added at an equivalent dilution in control experiments. In vivo, SW620 cells with high FGFR1 expression were subcutaneously implanted into the thighs of female NU–A/A Tyrc/Tyrc Foxn1nu/Foxn1nu mice. Once tumors reached 150 mm3, animals were randomized to receive either OM-RCA-01 (30 mg/kg, intraperitoneally, twice weekly for 3 weeks) or saline control. Tumor volumes were measured every 3 days over a 4-week period. Results: In vitro, FGF2 stimulation markedly increased proliferation, which was dose-dependently inhibited by OM-RCA-01 (EC50 = 4.3 × 10-5 g/ml). In Patient experiment 1, spheroid formation could not be established under FGFR1 inhibition, whereas robust spheroid growth was observed in the control group. In Patient 2, spheroids initially formed but ceased growing after 10 days of treatment with the FGFR1 inhibitor. In vivo, FGFR1 inhibition with OM-RCA-01 significantly suppressed tumor growth compared to control (P < 0.0001). Median tumor volume at study endpoint was 956.7 mm3 in the treatment group versus 2129.9 mm3 in vehicle. No tumors in the antibody-treated group exceeded 2000 mm3, whereas all control tumors reached this size by day 28. Conclusion: Selective inhibition of the FGFR1 extracellular domain with OM-RCA-01 effectively suppressed FGF2-driven proliferation in vitro, blocked patient-derived CRC spheroid growth, and significantly reduced tumor growth in vivo. These findings support OM-RCA-01 as a promising targeted therapy for FGFR1-expressing CRC. Citation Format: Yulia Khochenkova, Dmitry Khochenkov, Yuliya Baula, Qingqing Wang, Ilya Tsimafeyeu. Extracellular FGFR1 inhibition with OM-RCA-01 humanized antibody suppresses tumor growth in FGFR1-expressing colorectal cancer models [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr A138.