Patients received cibisatamab with escalating doses of FAP-4-1BBL weekly or every 3 weeks after obinutuzumab pretreatment to mitigate anti-drug antibody formation. These findings demonstrate the feasibility of combining tumor antigen-directed T cell engagement with localized co-stimulation, with evidence of immune activation and preliminary antitumor activity supporting further clinical development. ClinicalTrials.gov identifier: NCT04826003 .

P1, N=213, Active, not recruiting, Bristol-Myers Squibb | Recruiting --> Active, not recruiting

This adaptable and physiologically relevant model provides a platform to dissect the complex interplay between human tumors, immune cells, and immunotherapies and has the potential to significantly improve the translation of preclinical findings to the clinic.

The combination of FAP-IL2v plus atezolizumab with or without bevacizumab was consistent with the known safety profile of the individual drugs. The maximum tolerated dose was not reached, with a recommended FAP-IL2v dose of 10 mg. ORR was higher among patients receiving the triplet therapy compared with the doublet. Pharmacodynamic results were consistent with the mechanism of action of IL-2, supporting further research in this field.

P1, N=105, Recruiting, Immunome, Inc. | Not yet recruiting --> Recruiting

P=N/A, N=30, Recruiting, Children's Hospital Medical Center, Cincinnati | Not yet recruiting --> Recruiting

P1, N=410, Recruiting, Karolinska University Hospital | Not yet recruiting --> Recruiting

[177Lu]Lu-RTX-2358 demonstrated a manageable safety profile in a series of patients who were heavily pretreated for their disease. Given a promising therapeutic index as a result of prolonged retention in tumors and clearance from normal organs, further clinical evaluation is warranted.

P1, N=56, Recruiting, 3B Pharmaceuticals GmbH | Not yet recruiting --> Recruiting

Various FAPI radiotracers, including FAPI-04, FAPI-46, and FAP-2286, offer unique pharmacokinetic properties...However, challenges remain, including FAP expression heterogeneity and the need for optimized treatment protocols. The aim of this review is to provide a comprehensive overview of the current evidence and future directions of FAPI-based theranostics in sarcoma management, highlighting its potential to improve patient outcomes.

P1/2, N=36, Recruiting, Novartis Pharma AG

A therapy experiment in immunocompetent mice bearing low FAP-expressing tumors showed that the combination with L19-hIL2 potentiated the antitumoral activity of 177Lu-OncoFAP-23 and OncoFAP-GlyPro-MMAE. These results provided the motivation for the clinical development of these combinations for treating FAP-positive solid tumors.