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.
Authors
- Ettore Gilardoni (ORCID: https://orcid.org/0000-0002-2010-2667)
- Francesco Bartoli (ORCID: https://orcid.org/0000-0002-2702-3259)
- Samuele Cazzamalli (ORCID: https://orcid.org/0000-0003-0510-5664)
- Luigi Auletta (ORCID: https://orcid.org/0000-0002-1624-4240)
- Beatrice Zoanni (ORCID: https://orcid.org/0000-0003-0547-7767)
- Pinuccia Faviana (ORCID: https://orcid.org/0000-0003-4283-1083)
- Roberta Ferrari (ORCID: https://orcid.org/0000-0002-7960-6165)
- Matilde Bocci (ORCID: https://orcid.org/0000-0003-0317-4535)
- Maurizio Longo (ORCID: https://orcid.org/0000-0002-6838-8430)
- Damiano Stefanello (ORCID: https://orcid.org/0000-0003-2726-0366)
- Silvia Dell’Aere (ORCID: https://orcid.org/0000-0003-4927-7580)
- Alessandra Ubiali (ORCID: https://orcid.org/0000-0002-5704-6590)
- D Neri
- Paola Roccabianca
- Emanuele Marsala
- Elisa M. Gariboldi
- Andrea Galbiati (ORCID: https://orcid.org/0000-0003-0725-0726)
Institutions
- University of Pisa (IT)
- University of Milan (IT)
- Philogen (Italy) (IT)
- Philochem (Switzerland) (CH)
- Advanced Materials and Technologies (Slovenia) (SI)
- Azienda Ospedaliera Universitaria Pisana (IT)
- École Polytechnique Fédérale de Lausanne (CH)
Publication Details
- Journal
- Journal of Medicinal Chemistry
- Published
- 2026-05-16
- DOI
- https://doi.org/10.1021/acs.jmedchem.6c00682
- Primary Topic
- Peptidase Inhibition and Analysis
- Type
- article
- Field-Weighted Citation Impact
- 0.00