2ⁿᵈ Edition of the Cancer R&D World Conference 2026

Abstract

Background: Fibroblast growth factor receptor 1 (FGFR1) is a key mediator of tumor cell growth, vascularization, and immune evasion. OM-RCA-01 is a humanized monoclonal antibody designed to selectively bind FGFR1 with high affinity (Kd ~1.6 nM), thereby inhibiting ligand-dependent receptor activation. This study integrates preclinical findings across multiple tumor types to evaluate its therapeutic activity and its potential to augment immunotherapy.

Methods: Antitumor activity was investigated in FGFR1-positive cancer cell lines and organoid systems using proliferation assays and analyses of FGFR1 phosphorylation. In vivo efficacy was assessed in several models, including Caki-1 renal cell carcinoma xenografts, A549 lung cancer xenografts, SW620 colorectal cancer xenografts, and an FGFR1/PD-L1-positive lung adenocarcinoma patient-derived xenograft in humanized mice. Anti-angiogenic effects were examined using Matrigel assays. Immunomodulatory activity was evaluated in mixed lymphocyte reaction and SEB-stimulated PBMC assays in combination with nivolumab. Pharmacokinetics and safety were characterized in rodent and rabbit studies.

Results: OM-RCA-01 effectively suppressed FGF-mediated tumor cell proliferation and reduced FGFR1 phosphorylation in renal and lung cancer models. In A549 cells, the GI50 was approximately 9.7 µg/mL, while in Caki-1 cells growth inhibition was observed across a range of 1–100 µg/mL, with corresponding inhibition of receptor phosphorylation at nanomolar concentrations. In vivo, treatment with OM-RCA-01 significantly inhibited tumor growth in renal and lung xenografts and reduced angiogenesis in Matrigel assays. In colorectal cancer models, the antibody markedly decreased tumor burden and disrupted the growth of FGFR1-positive organoids. Immunologically, combining OM-RCA-01 with nivolumab enhanced cytokine production, including IFNγ and IL-2. In a humanized lung PDX model, combination therapy with pembrolizumab resulted in substantially greater tumor growth inhibition compared to checkpoint blockade alone. The compound was well tolerated, with favorable pharmacokinetic properties and no significant toxicity observed.

Conclusions: OM-RCA-01 exhibits broad antitumor activity through inhibition of FGFR1 signaling, suppression of angiogenesis, and potentiation of immune checkpoint inhibitors. These findings support its continued clinical development. An ongoing phase 1b/2 study (TAGNOT) is currently evaluating OM-RCA-01 in patients with FGFR1-expressing malignancies.