A Small-Molecule Drug Conjugate Targeting FAP Exhibits Potent Activity in Dogs with Spontaneous Tumors

Antibody-drug conjugates have transformed the treatment of cancer, yet their clinical utility can be limited by suboptimal tumor penetration, complex manufacturing, and safety concerns. Replacing antibodies with low-molecular-weight ligands enables the generation of small molecule-drug conjugates with enhanced tumor-targeting performance. Here, we report the results of a proof-of-concept study in canine cancer patients with OncoFAP glidotin, a small molecule-based targeted cytotoxic directed against Fibroblast Activation Protein. OncoFAP glidotin was evaluated in a dose-escalation trial in eight client-owned pet dogs bearing spontaneous FAP-positive tumors. The agent displayed an excellent safety profile, with no severe treatment-related adverse events. Six (75%) patients responded to the therapy. A tumor volume reduction of up to ∼88% in target lesions was observed on whole-body computed tomography, after only 4 weeks of treatment. These findings support further translational development activities of OncoFAP glidotin for both human and veterinary cancer patients.